Title of Invention	PYRROLOPYRIDAZINE DERIVATIVES
Abstract	The present invention relates to compound of the formula (I) or its salt, in which R<SUP>1</SUP> R<SUP>2</SUP>, R<SUP>3</SUP> and R<SUP>4</SUP> are as defined in the description, and to the process for their preparation.

Full Text

This invention relates to new pyrrolopyridazine derivatives and pharmaceuticalLY acceptable salts thereof which inhibit enzymatic activity of phosphodiesterase IV (PDE IV) and production of tumor necrosis factor-α (TNF-a). BACKGROUND ART Cyclic adenosine monophosphate (adenosine 3, 5'-cyclic monophosphate, "cAMP" or "cyclic AMP") is known as an intracellular second messenger, which is intermediated by a first messenger (hormone, neurotransmitter or autacoid) and the cellar responses. The first messenger stimulates the enzyme responsible for synthesis of cAMP. and then the cAMP intervenes in many functions such as metabolic, contractile or secretory. The effect of cAMP end when it is degraded by cyclic nucleotide phosphodiesterases, in particular phosphosieslerase-4 (PDE4 or PDE-IV), which is specific for cAMP. PDE-IV have been identified in many tissues including the central nervous systems, the heart, vascular smooth muscle, airway smooth muscle, myeloid lines, lymphoid, and the like. Evaluation of cAMP level by using the PDE-IV inhibitor would produce beneficial effect on inappropriate activation of airway smooth muscle and a wide variety of inflammatory cells. A major concern with the use of PDE-IV inhibitors is the side effect of emesis which has been observed for several candidate compounds as described in CBumouf et al, (Ann. Rep. In Med. Chem., 33:91-109(1998)). Burnouf describe the wide variation of the severity of the undesirable side effects exhibited by various compounds. Some condensed heterocyclic derivatives having the inhibitory activity of PDE-IV have been known, for example in WO03/016279, WO03/018579, WO03/000679 and the like. However, there remains a need for novel compounds that inhibit PDE-IV with minimal side effects. Although some pyrrolopyridazine derivatives having the inhibitory activity of hydroxymethylglutaryl (HMG) CoA reductase have been known, for example, in WO91/18903, pyrrolopyridazine derivatives having the inhibitory activity of PDE-IV have not been known. DISCLOSURE OF INVENTION This invention relates to new pyrrolopyridazine derivatives. The compounds of this invention inhibit cAMP phosphodiesterase enzyme m particular phosphodiesterase-4 enzyme, and also inhibit the production of tumor nu factor-α (TNF-α), a serum glycoprotein. Accordingly, one object of this invention is to provide the new and useful pyrrolopyridazine derivatives and pharmaceutically acceptable salts thereof which possess a strong phosphodicstcrase-4 (PDE lV)-inhibitory activity and a strong in activity on the production of tumor necrosis factor (TNF). Another object of this invention is to provide processes for preparation pyrrolopyridazine derivatives and salts thereof. A further object of this invention is to provide a pharmaceutical compos comprising said pyrrolopyridazine derivatives or a pharmaceutically acceptable sal' thereof. Still further object of this invention is to provide a use of said pyrrolopyridazine derivatives or a pharmaceutically acceptable sail as a medicament for prophylactic and therapeutic treatment of PDE-IV and TNI mediated diseases such as chronic inflammatory diseases, specific autoimmune ,r es, sepsis-induced organ injury, and the like in human being and animals. The object pyrrolopyridazine derivatives of the present invention arecan be represented by the following general formula (I): is optionally interrupted by amino or sulfonyl and optionally fuse with benzene ring, and also is optionally substituted by the group consisting of lower alky], hydroxy, oxo and lower alkoxy, Suitable pharmaceutically acceptable salts of the object compound (I) are conventional non-toxic salts and may include a salt with a base or an acid addition salt such as a salt with an inorganic base, for example, an alkali metal salt (e.g., sodium salt, potassium salt, etc.), an alkaline earth metal salt (e.g., calcium salt, magnesium salt, etc.), an ammonium salt; a salt with an organic base, for example, an organic amine salt (e.g., triethylamine salt, pyridine salt, picoline salt, ethanolamine salt, triethanolamine salt, dicyclohexylamine salt, N,N'-dibenzylethylenediamine salt, etc.); an inorganic acid addition salt (e.g., hydrochloride, hydrobromide, sulfate, phosphate, etc.); an organic carboxylic or sulfonic acid addition salt (e.g., formate, acetate, trifluoroacetate, maleate, tartrate, fumarate, methanesulfonate, benzenesulfonate, toluenesulfonate, etc.); a salt with a basic or acidic amino acid (e.g., arginine, aspartic acid, glutamic acid, etc.). The "prodrug" means the derivatives of the object compound (I) having a chemically or metabolically degradable group, which became pharmaceutically active after chemo- or biotransformation. in which R1 is (1) carboxy or esterified carboxy (more preferably, ethoxycarbonyl), (2) -CONR5R6 [whei ein R' and R1 each independently represents lower alky], or alternatively R5 and R, together with nitrogen atom to which they are attached represents saturated 5- or 6-membered heteromonocyclic group containing 1 to 2 nitrogen atom(s).] (more preferably, dimethylcarbamoyl or 1-pyrrolidinylcarbonyl), (3) hydroxy or lower alkoxy, (4) amino, cyclo(lower)alkylamino, or mono- or di(Iower)alkylamino optionally substituted by lower alkoxy, (5) trihalo(lower)alkyl, (6) trihalo(lower)alkylsulfonyloxy or arylsulfonylarnino, (7) lower alkyl optionally substituted by (i) halogen; (ii) carboxy; (iii) protected carboxy; (iv) cyano; (v)'carbamoyl; (vi) -OCONR15R16) [wherein R15 and R16 each independently represents hydrogen, aryl or lower alkyl optionally substituted by aryl, or R15 and R16, together with the nitrogen atom to which they are attached, represents saturated 5- or 6-membered heteromonocyclic group containing 1 to 2 nitrogen atom(s) and also optionally containing oxygen atom.] (more preferably, dimethylcarbamoyloxy, methyl-phenylcarbamoyloxy, morpholinylcarbonyloxy orpyrrolidinylcarnbonyloxy); (vii) lower alkylthio; (viii) lower alkylsulfonyl; (ix) lower alkylsulfonyloxy; (x) lower alkylsulfonylamino; (xi) mono- or di(lower)alkylamino optionally substituted by hydroxy, lower alkoxy, aryloxy, or substituted or unsubstituted aryl; (xii) amino; (xiii) acylamino (more preferably, lower alkanoylamino such as acetylamino, aroylamino such as benzoylamino, or heterocycliccarbonylamino such as pyrazinylcarbonylamino); (xiv) protected amino such as phthalimide, benzylamino or lower alkoxycarbonylamino; (xv) hydorxy; (xvi) acyloxy (more preferably, lower alkanoyloxy such as acetyloxy); (xvii) cyclo(lower)alkyloxy; (xviii) aryloxy; (xix) substituted or unsubstituted aryl (more preferably, phenyl); (xx) saturated or unsaturated 5- or 6-membered heteromonocyclic group containing 1 to 3 nitrogen atom(s) and also optionally containing oxygen atom or sulfur atom (more preferably, pipcrazinyl, morpholinyl, oxazolidinyl, thiomorpholinyl, piperidinyl, pyrrolidinyl or iriazolyl) optionally substituted by lower alkyl, hydroxy(lower)alkyl, aryl or oxo; or (xxi) lower alkoxy optionally substituted by carboxy, protected carboxy, hydroxy, protected hydroxy, lower alkoxy, cyclo(lower)alkyl, substituted or unsubstituted aryl (more preferably, phenyl optionally substituted by cyano, carboxy, protected carboxy or carbamoyl), saturated or unsaturated 5- or 6-membered heteromonocyclic group containing 1 to 2 nitrogen atom(s) (more preferably, pyridinyl, pyrazinyl or piperazinyl) optionally substituted by lower alky], or -CONR13R14 [wherein R13 and R14 each independently represents hydrogen or lower alkyl optionally substituted by aryl, or R13 and Ri4, together with the nitrogen atom to which they are attached, represents saturated 5- or 6-rnembered heteromonocyclic group containing 1 to 2 nitrogen atom(s) and also optionally containing oxygen atom.] (more preferably, carbamoyl, metbylcarbamoyl, benzylcarbamoyl or morpholinylcarbonyl), (8) aryl (more preferably, phenyl) optionally substituted by the substituent(s) selected from the group consisting of halogen, or (9) saturated or unsaturated 5- or 6-membered heteromonocyclic group (more preferably, pyrrolidinyl, pyrrolyl, oxazolyl, isooxazolyl, R7 is (1) hydrogen, (2) aryl (more preferably, phenyl) optionally substituted by lower alkoxy, (3) unsaturated heteromonocyclic group containing 1 to 2 nitrogen atom(s). (more preferably, pyridinyl), (4) carboxy, esterified carboxy (more preferably, lower alkoxycarbonyl) or - CONR10Rn [wherein R10 and R11 each independently represents hydrogen, lower alkylsulfonyh unsaturated heteromonocyclic group containing 1 to 2 nitrogen atom(s) such as pyridinyl or lower alkyl optionally substituted by hydroxy, alkoxy, carboxy, protected carboxy, sulfo or -R17, or alternatively R10 and R11, together with the nitrogen atom to which they are attached, represents saturated 5- or 6-membered heteromonocyclic group containing 1 to 2 nitrogen atom(s) and also optionally containing oxygen atom such as morpholinyl.], (5) acyl (e.g. lower alkanoyl such as formyl or acetyl, and heterocycliccarbonyl such as pyridinylcarbonyl) or halocarbonyl, (6) cyano, (7) amino, protected amino such as lower alkoxycarbonylamino, or mono- or di(lower)alkylamino, (8) hydroxy, aryloxy, acyloxy or lower alkoxy optionally substituted by hydroxy or acyloxy (e.g. lower alkanoyloxy), (9) lower alkylthio, lower alkylsulfinyl or lower alkylsulfonyl, or (10) -O-R12, or R and R2are combined together to form lower alkylene or lower alkenylen group which is optionally interrupted by amino or sulfonyl and also is optionally substituted by the group consisting of lower alkyl, hydroxy, oxo and lower alkoxy, R3 is (1) aryl (more preferably, phenyl or naphthyl) optionally substituted by at least one substituent(s) selected from the group consisting of (i) halogen, (ii) carboxy, (iii) protected carboxy, (iv) cyano, (v) -CONR!5R16 [wherein R15 and R16 each independently represents hydrogen, lower alkyl optionally substituted by hydroxy], (vi) lower alkyl, (vii) cyclo(lower)alkyl, (viii) hydroxy(lower)alkyl, (ix) lower alkoxy, (x) trihalo(lower)alkyl, (xi) unsaturated 5- or 6-membered heterornonocyclic group containing 1 to 2 oxygen atom(s) and 1 to 2 nitrogen atom(s) such as oxazolyl, (xii) lower alkylsulfonyl, (xiii) nitro, (xiv) sulfamoyl, and (xv) protected sulfamoyl; or (2) heterocyclic group selected from the group consisting of pyridinyl, pyrazinyl, oxazolyl, isooxazolyl, furanyl, thienyl, quinolyl, benzofuranyl and benzothienyl, wherein said heterocyclic group is optionally substituted by at least one substituent(s) selected from the group consisting of (i) lower alkyl, (ii) cyclo()ower)alkyl, (iii) lower alkoxy, (iv) acyl such as lower alkanoyl, (v) amino, (vi) mono- or di(lowcr)alky]amino, (vii) protected amino such as lower alkoxycarbonylamino, (viii) cyano, (ix) carboxy, (x) protected carboxy such as ethoxycarbonyl or methoxycarbonyl, (xi) -CONR15R16 [wherein RI5andR16 each independently represents hydrogen, lower alkyl optionally substituted by hydroxy], (xii) lower alkenyl optionally substituted by lower alkoxy, (xiii) halogen, (xiv) lower alkylthio and (xv) hydroxy; R4 is hydrogen, halogen, cyano, carbamoyl, lower alkanoyl, thiocyanate, lower alkylthio, lower alkenyl, hydroxyl(Jower)alkyl, trihalo(lower)alkyl or lower alkyl, and 1 *) 1 "7 R " and R are each independently a group derived from protected or unprotected sugar such as galactose by removal of the hydroxy group therefrom, or a pharmaceutically acceptable salt thereof. More preferred compounds of formula (I) are those in which: R1 is (1) mono- or di(lower)aIkylamino, (2) aryl such as phenyl, (3) satulated or unsaturated 5 to 6 membered heteromonocyclic group containing 1 to 2 hetero atom(s) selected from nitrogen, oxygen or sulfur atom(s) (more preferably, pyrrolidinyl, pyrrolyl, oxazolyl, isooxazolyl, thiazolyl, furanyl, thienyl, pyridinyl,elc), or (4) lower alkyl optionally substituted by lower alkoxy or saturated 5- or 6-rnembered heteromonocyclic group containing 1 to 2 nitrogen atom(s) and also optionally containing oxygen atom (more preferably, piperazinyl or morpholinyl), wherein lower alkoxy is optionally substituted by cyclo(lower)alkyl or unsaturated 5 to 6 membered heteromonocyclic group containing 1 to 2 nitrogen atom(s) (more preferably, pyridinyl), R2 is R7 or -A2-R7, wherein A2 is -(CH,)n- or -(CH=CH)m- [wherein n is integer which may range 2 to 6 and m is integer of 1 or 2, and R7 is hydrogen, lower alkylsulfonyl, carboxy, protected carboxy or unsaturated 5 to 6 membered heteromonocyclic group containing 1 to 2 nitrogen atom(s) (more preferably, pyridinyl), R3 is (1) aryl optionally substituted by lower alkyl, cyclo(lower)alkyl, halogen, cyano or carbamoyl; or (2) unsaturated condensed heterocyclic group containing 1 to 2 nitrogen atom(s) (more preferably, quinolinyl); or unsaturated 5 to 6 membered heteromonocyclic group containing at least one nitrogen atom(s) (more preferably, 3-pyridinyl and 4-pyridinyl) substituted by lower alkyl, cyclo(lower)alky! or halogen, and R4 is lower alkyl. Most preferred compounds of formula (I) are those in which: R1 is phenyl, satulated or unsaturated 5 to 6 membered heteromonocyclic group containing 1 to 2 hetero atom(s) selected from nitrogen, oxygen or sulfur atom(s) (more preferably, pyrrolyl, isooxazolyl, furanyl, thienyl, etc.) or lower alkyl optionally substituted by lower alkoxy or saturated or saturated 5- or 6-rnembered heteromonocyclic group containing 1 to 2 nitrogen atom(s) and also optionally containing oxygen atom (more preferably, piperazinyl or morpholinyl), wherein lower alkoxy is optionally substituted by cyclo(lower)alkyl or unsaturated 5 to 6 membered heteromonocyclic group containing at least one nitrogen atom(s) (more preferably, pyridinyl), "7 "7 R2 is -(CH2)n-R , wherein n is integer which may range 2 to 5, and R is carboxy or protected carboxy, R3 is (1) phenyl optionally substituted by lower alkyl, cyclo(lower)alkyl, lower alkoxy, halogen, cyano or carbamoyl; or (2) unsaturated 5 to 6 membered heteromonocyclic group containing at least one nitrogen atom(s) (more preferably, 3-pyridinyl and 4-pyridinyl) substituted by lower alkyl, cyclo(lower)alkyl, lower Both of the above tautomeric isomers are included within the scope of the present invention, and in the present specification and claims, however, the object compound (I) is represented for convenience' sake by one expression of the possible tautomeric forms of pyrrolopyridazine ring. In the above and subsequent descriptions of the present specification, suitable examples and illustration of the various definitions which the present invention intends to include within the scope thereof are explained in detail as follows. The term "lower" is used to intend a group having 1 to 6, preferably 1 to 4, carbon atom(s), unless otherwise provided. Suitable "lower alkyl" and "lower alkyl moiety" may include straight or branched one having 1 to 6 carbon atom(s), such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, tert-penlyl, hexyl, and the like, and in which more preferable example may be C1-C4 alkyl. Suitable "lower alkenyl" may include vinyl(ethenyl), l-(or 2-)propenyl, l-(or 2- or 3-)butenyl, l-(or 2- or 3- or4-)pentenyl, l-(or 2- or 3- or 4-or 5-)hexenyl, 1-methylvinyl, 1-ethylvinyl, l-(or 2-)rnethy]-l-(or 2-)propenyl, l-(or 2-)ethyl-1-(or 2-)propenyl, l-(or 2-or 3-)rnethyI-l-(or 2- or 3-)butenyl, and the like, in which more preferable example may be C2-C4 alkenyl. Suitable "lower alkynyl" may include ethynyl, 1-propynyl, propargyl, 1-methylpropargyl, ] or 2 or 3-bulynyl, 1 or 2 or 3 or4-pentynyl, 1 or 2 or 3 or 4 or 5-hexynyl, and the like. Suitable "lower alkylene" may include straight or branched one such as methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, methylmethylene, ethylethylene, propylene, and the like, in which more preferable example may be C1-C4 alkylene and the most preferable one may be methylene. Example of hydroxy(C1-C2)alkylene is hydroxymethylene, (hydroxymethyl)methylene or l-(or 2-)hydroxyethylene. Suitable "lower alkoxy" may include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, t-butoxy, pentyloxy,t-pentyloxy, hexyloxy and the like. Suitable "halogen" and "halogen moiety" may include fluorine, bromine, chlorine and iodine. Suitable "trihalo(lower)alkyl" may include trichloromethyl, trifluoromethyl, trichloroethyl, tribromoethyl, and the like. Suitable "mono- or di(lower)alkylamino" may include amino group substituted by one or two lower alkyl such as methylamino, ethylamino, dimethylamino, and the like. Example of "mono- or di(lower)alkylamino substituted by lower alkoxy" may be methoxymetylamino,methoxyethylamino,methoxyethyl(methyl)amino, methoxyethyl(ethyl)amino,di(methoxyethyl)amino,ethoxymethylamino, ethoxyethylamino, and the like. Suitable "lower alkylthio" may include conventional ones such as methylthio, ethylthio, propylthio, butylthio, and the like. Suitable "lower alkylsulfinyl" may include conventional ones such as rnethylsulfinyl, ethylsulfinyl, propylsulfinyl, butylsulfinyl, and the like. Suitable "lower alkylsulfonyl" may include conventional ones such as methylsulfonyl, ethylsulfonyl, propylsulfonyl,bytylsulfonyl, and the like. Suitable "trihalo(lower)alkylsulfonyloxy"may include sulfonyloxy group substituted by trihalo(lower)alkyl such as trifluoromethylsulfonyloxy, trifluoroethylsulfonyloxy, trichloromethylsulfonyloxy, and the like. Suitable "protected carboxy" and "protected carboxy moiety" may include esterified carboxy and the like. And suitable example of said ester may be the ones such as lower alkyl ester (e.g., methyl ester, ethyl ester, propyl ester, isopropyl ester, butyl ester, isobutyl ester, t-butyl ester, pentyl ester, l-pentyl ester, hexyl ester, etc.); lower alkenyl ester (e.g., vinyl ester, allyl ester, etc.); lower alkyny] ester (e.g. elbynyl ester, propynyl ester, etc.); i lower alkoxy(lower)alkyl ester (e.g., methoxymelhyl ester, elhoxymethyl ester, isopropoxymethyl ester, 1-melhoxyethy] ester, 1-elhoxyethy) ester, etc.); lower alkylthio(lower)alkyl ester (e.g., methylthiometbyl ester, ethylthiomelhyl ester, ethyllhioethyl ester, isopropoxythiomethyl ester, etc.); mono(or di or lri)halo(lower)alkyl ester (e.g., 2-iodoethyl ester, 2,2,2-trichloroethyl ester, etc.); lower alkanoyloxy(lower)alkyl ester (e.g., acetoxymethyl ester, propionyloxymethyl ester, butyryloxymethyl ester, valeryloxymethyl ester, pivaloyloxymethyl ester, hexanoyloxymethyl ester, 1-acetoxyethyl ester, 2-acetoxyethyl ester, 2-propionyloxyethyl ester, etc.); lower alkoxycarbonyloxy(lower)alkyl ester (e.g., methoxycarbonyloxymethyl ester, ethoxycarbonyloxymethyl ester, propoxycarbonyloxymethyl ester, l-(or2-)- [methoxycarbonyloxy]ethyl ester, l-(or 2-)-[ethoxycarbonyloxy]ethyl ester, l-(or 2-)- [propoxycarbonyloxyjethyl ester, l-(or 2-)-[isopropoxycarbonyloxy]ethyl ester, etc.); lower alkanesuIfonyl(lower)alkyl ester (e.g., mesylmethyl ester, 2-mesylethyJ ester, etc.); lower alkoxycarbonyloxy(lower)alkyl ester (e.g., methoxycarbonyloxymethyl ester, ethoxycarbonyloxymethyl ester, propoxycarbonyloxymethyl ester, t-butoxycarbonyl- oxymethy] ester, l-(or 2-)methoxycarbonyloxyethyl ester, l-(or2- )ethoxycarbonyloxyethyl ester, l-(or 2-)-isopropoxycarbonyloxyethyl ester, etc.); phthalidylidene(lower)alkyl ester; (5-lower alkyl-2-oxo-l,3-dioxoI-4-yI)(lower)alkyl ester [e.g., (5-methyl-2-oxo-l,3- dioxol-4-yl)methyl ester, (5-ethyl-2-oxo-l,3-dioxol-4-yl)methyl ester, (5-propyl-2-oxo- l,3-dioxol-4-yl)ethyl ester, etc.]; mono(or di or tri)aryl(lower)alkyl ester, for example, mono(or di or tri)phenyl(lower)alkyl ester which may have one or more suitable substituent(s) (e.g., benzyl ester, 4-methoxybenzyl ester, 4-nitrobenzyl ester, phenethyl ester, trityl ester, benzhydryl ester, bis(methoxyphenyl)methyl ester, 3,4-dimethoxybenzyI ester, 4- hydroxy-3,5-di-t-butylbenzyl ester, etc.); aryl ester which may have one or more suitable substituent(s) such as substituted or unsubstituted phenyl ester (e.g., phenyl ester, tolyl ester, t-butylphenyl ester, xylyl ester, mesityl ester, cumenyl ester, 4-chlorophenyl ester, 4-methoxyphenyl ester, etc.); tri(lower)alkylsilyl ester (e.g. trimethylsilyl ester, triethylsilyl ester, etc.); tri(lowcr)alkyIsilyI(lower)alkyl ester (e.g. 2-lrimethylsilylethyl ester, etc.); and the like, in which more preferable example may be lower alkyl ester, i.e., lower alkoxycarbonyl (e.g. ethoxycarbonyl, etc.). The term "protected amino" means an amino group bonded to the amino-protecting group. Example of such amino-protectnig group include lower alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, t-butoxycarbonyl, etc.); lower alkenyloxycarbonyl (e.g. vinyloxycarbonyl, allyloxycarbonyl, etc.); optionally substituted aryl(lower)alkoxycarbonyl (e.g. benzyloxycarbonyl, etc.); phthalimide; and the like. Further example of amino-protecting group are well-known in organic synthesis and are described by T. W. Greene and P. G. M. Wuts, "Protective Groups in Organic Synthesis," Second Edition, John Wiley and Sons, New York, N.Y., which is herein incorporated by reference. The term "protected sulfamoyl" means sulfamoyl group having the amino-protecting group mentioned above on the nitrogen atom. A preferred amino-protecting group is aryl(lower)alkoxycarbonyl (e.g. benzyloxycarbonyl, etc.); and the like. Suitable "acyl" and "acyl moiety" may include aliphatic acyl group, and acyl group containing an aromatic ring, which is referred to as aromatic acyl, or heterocyclic ring, which is referred to as heterocyclic acyl. Suitable example of said acyl may be illustrated as follows: Aliphatic acyl such as lower or higher alkanoyl (e.g., formyl, acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 2,2-dimethylpropanoyl, hexanoyl, heptanoyl, octanoyl, nonanoy], decanoyl, undecanoyl, dodecanoyl, tridecanoyl, tetradecanoyl, pentadecanoyl, hexadecanoyl, heptadecanoyl, octadecanoyl, nonadecanoyl, icosanoy], etc.); in which preferable "lower alkanoyl" may include straight or branched one such as formyl, acetyl, propionyl, butyryl, and the like, lower or higher alkenoyl (e.g., acryloyl, 2-(or 3-)-butenoyl, 2-(or 3- or 4-)pentenoyl, 2-(or 3- or 4- or 5-)-bexenoyl, etc.); lower alkadienoyl (e.g., heptadienoyl, hexadienoyl, etc.); cyclo(lower)alkylcarbonyl (e.g., cyclopropylcarbonyl, cyclopenlylcarbonyl, cyclohexylcarbonyl, etc.); lower alkylglyoxyloyl (e.g., methylglyoxyloyl, ethylglyoxyloyl, propylglyoxyloyl, etc.); lower alkoxyglyoxyloyl (e.g., methoxyglyoxyloyl, ethoxyglyoxyloyl, propoxyglyoxyloyl, etc.); or the like; Aromatic acyl such as aroy] (e.g., benzoyl, toluoyl,naphthoyl,etc.); ar(lower)alkanoyl [e.g.,phenyI(lower)alkanoyl (e.g.,phenylacetyl, phenylpropanoyl, phenylbutanoyl, phenylisobutanoyl, phenylpentanoyl, phenylhexanoyl, etc.), naphthyl(lower)alkanoyl (e.g., naphthylacetyl, naphthylpropanoyl, naphthylbutanoyl, etc.), etc.]; ar(lower)alkenoyl [e.g., pheny](lower)alkenoyl (e.g., phenylpropenoyl, phenylbutenoyl, phenylmethacryloyl, phenylpenlenoyl, phenylhexenoyl, etc.), naphthy](lower)alkenoyl (e.g., naphthylpropenoyl, naphtbylbutenoyl, etc.), etc.]; aryloxy(lower)alkanoyl (e.g., phenoxyacetyl, phenoxypropionyl, etc.); arylglyoxyloyl (e.g., phenylglyoxyloyl, naphthylglyoxyloyl, etc.); heterocyclic acyl such as heterocycliccarbonyl; heterocyclic(lower)alkanoyl (e.g., heterocyclicacetyl, heterocyclicpropanoyl, heterocyclicbutanoyl, heterocyclicpentanoyl, heterocyclichexanoyl, etc.); heterocyclic(lower)alkenoyl(e.g., heterocyclicpropenoyl,heterocyclicbutenoyl, heterocyclicpentenoy], heterocyclichexenoyl, etc.); heterocyclicglyoxyloyl; heterocyclicoxycarbonyl; or the like; in which suitable "heterocyclic moiety" may include saturated or unsaturated, monocyclic or polycyclic heterocyclic group containing at least one hetero-atom such as an oxygen, sulfur, nitrogen atom and the like, as mentioned below and preferable "heterocyclic¬carbonyl" may include carbonyl group substituted by heterocyclic group as mentioned below such as pyrrolidinylcarbonyl, pyridinylcarbonyl, pyrazinylcarbonyl, and the like.. Syitable "halocarbonyl" may include chlorocarbonyl, bromocarbonyl, and the like. Suitable "cyclo(lower)alkyl" and "cyclo(lower)alkyl moeity" may include one having 3 to 7 carbon atoms such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like. Suitable "aryl" and "aryl moiety" may include C6-C10 aryl such as phenyl, naphthyl and the like. Suitable "heterocyclic moiety" may include saturated or unsaturated, monocyclic or polycyclic heterocyclic group containing at least one hetero-atom such as an oxygen, sulfur, nitrogen atom and the like. Preferable heterocyclic group may be heterocyclic group such as (1) unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 4 nitrogen alom(s),for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazoly], pyridinyl, dihydropyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazolyl tetrazolyl (e.g., lH-tetrazolyl, 2H-tetrazolyI, etc.), etc.; (2) saturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 4 nitrogen atom(s),for example, pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl, etc.; (3) unsaturated condensed heterocyclic group containing 1 to 4 nitrogen atom(s), for example, indolyl, isoindolyl, indolinyl, indolizinyl, benzimidazolyl, quinolyl, tetrahydroquinolyl (e.g., 1,2,3,4-tetrahydroquinolyl, etc.), isoquinolyl, indazolyl, benzotriazolyl, benzopyrimidinyl (e.g., benzo[b]pyrimidinyl, etc.), etc.; (4) unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, oxazolyl,isoxazolyl,oxadiazolyl (e.g., 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5- oxadiazolyl, etc.), etc.; (5) saturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, rnorpholinyl, sydnonyl, etc.; (6) unsaturated condensed heterocyclic group containing 1 to 2 oxygen atom(s) and 1 to 3 nitrogen atom(s), for example, benzoxazolyl, benzoxadiazolyl, etc.; (7) unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, thiazolyl,isothiazolyl,thiadiazolyl (e.g., 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4- thiadiazolyl, 1,2,5-thiadiazolyl, etc.), dihydrothiazinyl, etc.; (8) saturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, thiazolidinyl,etc; (9) unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing 1 to 2 sulfur atom(s), for example, thienyl, dihydrodithiinyl, dihydrodilhionyl, etc.; (10) unsaturated condensed heterocyclic group containing 1 to 2 sulfur atom(s) and 1 to 3 nitrogen atom(s), for example, benzothiazolyl, benzothiadiazolyl, etc.; (11) unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing an oxygen atom, for example, furanyl, etc.; (12) unsaturated condensed heterocyclic group containing 1 to 2 oxygen atom(s), for example, benzodioxolyl (e.g. methylenedioxyphenyl, etc.), benzofuranyl, etc.; (13) unsaturated 3 to 8-membered (more preferably 5 or 6-membered) heteromonocyclic group containing an oxygen atom and 1 to 2 sulfur atom(s), for example, dihydrooxathiinyl, etc.; (14) unsaturated condensed heterocyclic group containing 1 to 2 sulfur alom(s), for example,benzothienyl (e.g., benzo[b]thienyl, etc.), benzodithiinyl, etc.; (15) unsaturated condensed heterocyclic group containing an oxygen atom and 1 to 2 sulfur atom(s), for example, benzoxathiinyl, etc.; and the like. Suitable "heterocyclic group" and "heterocyclic moiety" in the terms "heterocycliccarbonyl" can be referred to the ones as mentioned above. Suitable "N-containing heterocyclic group" and "N-containing heterocyclic moiety" can be referred to the ones as mentioned above, wherein the heterocyclic group is containing at least one nitrogen atom such as l-pyrrolidinyl, morpholinyl and the like. A group derived from a sugar may be the group derived from, for example, glyceraldehydes; an aldose such as erythrose, threose, arabinose, ribose, xylose, lyxose, glucose, mannose or galactose; a ketose such as fructose or sorbose; or a discccharide such as maltose, lactose or sucrose. Protecting groups for the hydroxy group of the above-mentioned sugars are an aliphatic acyl group, such as formyl, or acetyl; a cyclic ether group such as tetrahydro-2-furanyl ortetrahydro-2-pyranyl; a 1-alkoxyethyl group such as 1-melhoxyethyl or 1-ethoxyethyl; and a silyl group such as trimethylsilyl, triethylsilyl or t-butyldimethylsilyl. Suitable "substituted or unsubstituted lower alkyl" for R1 may include straight or branched lower alkyl (e.g. methyl, isopropyl, neopentyl, etc.) optionally substituted by; (1) halogen (e.g. fluoro, bromo, etc.), (2) carboxy, (3) protected carboxy (e.g. esterified carboxy such as ethoxycarbonyl, etc.), (4) cyano, (5) carbamoyl, (6) -OCONR R [wherein R15 and R16 each independently represents hydrogen, aryl or lower alkyl optionally substituted by aryl, or R " and R , together with the nitrogen atom to which they are attached, represents saturated 5- or 6-membcred heteromonocyclic group containing 1 to 2 nitrogen atom(s) and also optionally containing oxygen atom.] (more preferably, dimethylcarbamoyloxy,meUiyl-phenylcarbamoyloxy, morpholinylcarbonyloxy, pyrrolidinylcarnbonyloxy, etc); (7) lower alkylthio (e.g. methylthio, etc.), (8) lower alkylsulfonyl (e.g. methylsulfonyl, etc.), (9) lower alkylsulfonyloxy (e.g. methylsulfonyoxyl, etc.), (10) lower alkylsulfonylamino (e.g. methylsulfonylamino, etc.), (11) mono- or di(lower)alkylamino optionally substituted by hydroxy, lower alkoxy, acyloxy (e.g. phenoxy, etc.), or substituted or unsubstituted aryl (e.g. benzylamino, etc.), (12) amino; (13) acylamino (more preferably, lower alkanoylamino such as acetylamino, aroylamino such as benzoylamino, or heterocycliccarbonylamino such as pyrazinylcarbonylarnino, or the like), (14) protected amino (e.g., methoxycarbonylamino, phthalimide, etc.), (15) hydroxy, (16) acyloxy (more preferably, lower alkanoyloxy such as acetyloxy, or the like), (17) cyclo(lower)alkyloxy, (18) aryloxy (e.g. phenoxy, etc.) (19) substituted or unsubstituted aryl (more preferably, phenyl), (20) saturated or unsaturated 5- or 6-membered heteromonocyclic group containing 1 to 3 nitrogen atom(s) and also optionally containing oxygen atom or sulfur atom (more preferably, piperazinyl, rnorpholinyl, oxazolidinyl, thiomorpholinyl, piperidinyl, pyrrolidinyl or triazolyl) optionally substituted by lower alkyl, hydroxy(lower)alkyl, aryl or oxo, (21) lower alkoxy (e.g. methoxy, ethoxy, iso-propoxy, etc.) optionally substituted by carboxy, protected carboxy (e.g. tert-butoxycarbonyl, etc.), hydroxy, protected hydroxy (e.g. tetrahydro-2H-pyran-2-yloxy, etc.), cyclo(lower)alkyl (e.g. cyclopropyl, cyclohexyl, etc.), substituted or unsubstituted aryl (e.g. phenyl optionally substituted by cyano, carboxy, protected carboxy or carbamoyl, such as phenyl, 2-, 3- or 4-cyanophenyl, 2-, 3- or 4-carboxyphenyl, 2-, 3- or 4-(methoxycarbonyl)phenyl, 2-, 3- or 4-carbamoylphenyl, etc.), saturated or unsaturated 5- or 6-membered heterocyclic group containing 1 to 2 nitrogen atom(s) optionally substituted by lower (more preferably, 2-, 3- or 4-pyridinyl, pyrazinyl or 4-methylpiperazinyl)(e.g. 2-, 3- or 4-pyridinyl, pyrazinyl, etc.), or -CONR R [wherein R and R each independently hydrogen or lower alkyl optionally substituted by aryl, or R13 and R14, together with the nitrogen atom to which they are attached, represents N-containing heterocyclic group] (e.g. morpholinocarbonyl, dimethylcarbamoyl, etc.), and the like. Suitable "substituted or unsubstituted aryl" may include phenyl, naphthyl, etc.) optionally substituted by the substituent(s) selected from the group consisting of (1) halogen (e.g. fluoro, chloro, etc.), (2) carboxy, (3) protected carboxy, cyano, (5) -CONR15Ru [wherein R15 and R16 are each independently represents hydrogen, lower alkyl optionally substituted by hydroxy] (e.g. carbamoyl, hydroxyethylcarbamoyl, etc.), (6) lower alkyl (e.g. methyl, etc.), (7) cyclo(Iower)alkyl (e.g. cyclopropyl, etc) (8) lower alkoxy (e.g. methoxy, etc.), (9) trihalo(Iower)alkyl (e.g. trifluoromethyl, etc.), (10) heterocyclic group such as oxazolyl, (11) lower alkylsulfonyl (e.g. methylsulfonyl, etc.), (12) nitro, (13) amino, (14) sulfamoyl, and (15) protected sulfamoyl such as ar(lower)alkoxycarbonyl$ulfamoyl, and the like. In which, preferable example of "substituted or unsubstituted aryl" for R1 is aryl optionally substituted by the substituent(s) selected from the group consisting of halogen (e.g. phenyl, 4-fluorophenyl, etc.); preferable example of "substituted or unsubstituted aryl" for R3 is aryl optionally substituted by the substituent(s) selected from the group consisting of (1) halogen, (2) carboxy, (3) protected carboxy such as esterified carboxy (e.g. benzyloxycarbonyl, etc,), (4) cyano, (5) --CONR15R16 [wherein R15 and R36 are each independently represents hydrogen, lower alkyl optionally substituted by hydroxy], (6) lower alkyl, (7) cyclo(lower)alkyl, (8) lower alkoxy, (9) trihalo(lower)alkyl, (10) heterocyclic group, (11) lower alkyl sulfonyl, (12) nitro, (13) amino, (14) sulfamoyl, and (15) protected sulfamoyl, and the like. (e.g. phenyl, 2-naphthyl, 2- or 3-chlorophenyl, 2,3-, 2,4-, 3,4- or 3,5-dichlorophenyl, 3- or 4-fluorophenyl, 3- or 4-cyanophenyl, 3- or 4-carbamoylphenyl, 4-sulfamoylphenyl, 4-(benzyloxycarbonylsulfamoyl)phenyl, 3-carboxyphenyl, 3-(N-(2-hydroxyethyl)carbamoyl)phenyl, 3-nitrophenyl, 3-irifluoromethylphenyl, 3-methylsulfonylphenyl, 3-(5-oxazolyl)phenyl, 3-methoxyphenyl, 3-methylphenyl, etc.); and •7 preferable example of "substituted or unsubstituted aryl" for R is aryl optionally substituted by lower alkoxy (e.g. phenyl, 2-, 3- or 4-methoxyphenyl, etc.). Suitable "substituted or unsubstituted heterocyclic group" may include heterocyclic group mentioned above (more preferably, pyridinyl, pyrazinyl, oxazolyl, isooxazolyl, furanyl, thienyl, quinolinyl, benzofuranyl and benzothienyl), which is optionally substituted by the substituent(s) selected from the group consisting of (1) lower alkyl (e.g. methyl, etc.), (2) cyclo(lower)alkyl (e.g. cyclopropyl, etc.) (3) lower alkoxy (e.g. methoxy, etc.), (4) acyl (e.g. lower alkanoyl such as acetyl, etc.), (5) amino, (6) mono- or di(lower)alkylamino (e.g. dimethylamino, etc.), (7) protected amino (e.g. lower alkoxycarbonylamino such as tert-butoxycarbonylamino, etc.), (8) cyano, (9) carboxy, (10) protected carboxy (e.g. benzyloxycarbonyl, etc.), (11) -CONR15R16 [wherein R15 and R16 are each independently represents hydrogen, lower alkyl optionally substituted by hydroxy] (e.g. carbamoyl, hydroxyethylcarbamoyl, etc.), (12) lower alkenyl optionally substituted by lower alkoxy (e.g. vinyl, 1-ethoxyvinyl, etc.), (13) halogen (e.g. chloro, bromo, etc.), (14) lower alkylthio, (15) hydroxy, and the like. In which, preferable example of "substituted or unsubstituted heterocyclic group" for R1 is heterocyclic group optionally substituted by lower alkyl or halogen (e.g. 2-pyridinyl, 5-blomo-3-pyridinyl, l-methyl-2-pyrrolyl, 1-pyrrolyl, l-pyrrolidinyl,3-methyl-2-thienyl, 2-thienyl, 2- or 3-furanyl, 2-thiazolyl, 5-oxazolyl, 5-methyl-isooxazolyl, 3,5-dimethyl-4-isoxazolyl, etc.); and preferable example of "substituted or unsubstituted heterocyclic group" for R3 is heterocyclic group optionally substituted by at least one substituent(s) selected from the group consisting of (1) lower alkyl, (2) cyclo(lower)alkyl, (3) lower alkoxy, (4) acy] such as lower alkanoyl, (5) amino, (6) mono- or di(lower)alkylamino, (7) protected amino such as lower alkoxycarbonylamino, (8) cyano, (9) carboxy, (10) protected carboxy such as esterified carboxy (e.g. benzyloxycarbonyl), (11) carbamoyl, (12) lower alkenyl optionally substituted by lower alkoxy, (13) halogen, (14) lower alkylthio, and (15) hydroxy (e.g. 3- or 4-pyridyl, 2-pyrazinyl, 6-methoxy-2-pyrazinyl, 4- or 5-oxazolyl, 2-benzofuranyl, 2-benzothienyl, 3- or 6-quinolinyl, 2-chloro-4-pyridyl, 5-bromo-3-pyridyl, 5-chloro-2-thienyl, 5,6-dichloro-2-pyridyl, 4-chloro-2-pyridyl, 5-cyano-3-pyridyl, 5-carboxy-3-pyridinyl, 5-carbamoyl-3-pyridyl, 5-(benzyloxycarbonyl)-3-pyridyl, 5-(tert-butoxycarbonylamino)-3-pyridinyl, 5-amino-3-pyridinyl, 2-methoxy-4-pyridyl, 3-rnethoxy-5-isoxazolyl, 2-methylthio-4-pyridinyl, 2-hydroxy-4-pyridyl, 5-methyl-3-pyridyl, 5-ethyl-3-pyridyl, 5-methyl-3-isoxazolyl, 5-vinyl-3-pyridyl, 2-vinyl-4-pyridyl, 5-acetyl-3-pyridyl, 2-dimethylamino-4-pyridyl, 5-(l-ethoxyvinyl)-3-pyridyl, 2-oxo-l,2-dihydro-4-pyridyl, or 2-methylthio-4-pyridyl, etc.). R] and R2 are combined together to form lower alkylene or lower alkenylen group which is optionally interrupted by amino or sulfonyl and also is optionally substituted by the group consisting of lower alkyl, hydroxy, oxo and lower alkoxy, which is represented Suitable "leaving group" may include acid residue, lower alkoxy as exemplified above, and the like. The above Processes can be earned out according to a conventional manner such as the one described in Preparations and/or Examples, or in a similar manner thereto. Among the above Processes, fused heterocyclic ring forming processes (such as Process "1 and Process 12) are important for carrying out of this invention and are explained in more detail. According to the Process 1, pyrrolopyridazine derivatives (I) can be prepared by reacting the l-amino-2-acylpyrrole derivative (II) or a salt thereof and the compound (III) or a sail thereof in the presence of a catalytic amount of acid catalyst in an inert solvent, preferably with concomitant removal of the water being produced by physical (e.g. Dean-Stark trap) or chemical (e.g. molecular sieves) means. Suitable acid catalyst is, for example p-toluenesulfonic acid, rnethanesulfonic acid, hydrochloric acid, trifluoroacetic acid and so on. Suitable inert solvent is, for example, benzene, toluene, tetrahydrofuran and the like. Another ring forming process is descried in Process 12, in this process pyrrolopyridazine derivatives (I) can be also prepared reacting 1-aminopyrole derivative (V) or a salt thereof and (3-diketone derivative or a salt thereof under the similar condition before mentioned Process 1, and therefore the reaction conditions can be referred to those of the Process 1. The compounds of the present invention can be purified by any conventional purification methods employed for purifying organic compounds, such as re-crystallization, column chromatography, thin-layer chromatography, high-performance liquid chromatography and the like. The compounds can be identified by conventional methods such as NMR spectrography, mass spectrography, IR spectrography, elemental analysis, and measurement of melting point. Suitable salts of the object and the starting compounds in Processes 1 to 40 can be referred to the ones as exemplified for the compound (I). The new pyrrolopyridazine derivatives (I) and pharmaceutically acceptable salts thereof hardly possess a strong inhibitory activity against phosphodiesterase 111 (PDE III), but possess a strong inhibitory activity against phosphodiesterase IV (PDE IV) and a strong inhibitory activity on the tumor necrosis factor (TNF). That is, the pyrrolopyridazine derivatives (I) and pharmaceutically acceptable salts thereof are selective inhibitors of phosphodiesterase IV (PDE IV) and inhibitors on the production of tumor necrosis factor (TNF). Accordingly, the new pyrrolopyridazine derivatives (]) and a pharmaceutically acceptable salt thereof can be used for prophylactic and therapeutic treatment of PDE-IV and TNF mediated diseases such as chronic inflammatory diseases (e.g., rheumatoid arthrilis, osteoarthritis, emphysema, chronic bronchiolitis, allergic rhinitis, etc.), 3Steoporosis, rejection by transplantation, asthma, chronic obstructive pulmonary disease (COPD), eosinophilia, fibrotic disease (e.g., cystic fibrosis, pulmonary fibrosis, hepatic fibrosis, renal fibrosis, etc.), (viral alcoholic, drug-induced) acute and fulminant hepatitis, hepatic steatosis (alcoholic and non-alcoholic steato-hepatitis), chronic (viral and non-viral) hepatitis, hepatic cirrhosis, autoimmune hepatitis, pancreatitis, nephritis, endotoxin shock, specific autoimmune diseases [e.g., ankylosing spondylitis, autoimmune encephalomyelitis, autoimmune hematological disorders (e.g., hemolytic anemia, aplastic anemia, pure red cell anemia, idiopathic thrombocytopenia, etc.), systemic lupus erythematosus (SLE), polychondritis, scleroderma, Wegener granulomatosis, dermatomyositis, chronic active hepatitis (Wilson's disease, etc.), myasthenia gravis, idiopathic sprue, autoimmune inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease, etc.), endocrine ophthalmopathy, Grave's disease, sarcoidosis, multiple sclerosis, primary biliary cirrhosis, juvenile diabetes (diabetes mellitus type I), Reiter's syndrome, non infection uveitis, autoimmune keratitis (e.g., keratoconjunctivitis sicca, vernal keratoconjunctivitis, etc.), interstitial lung fibrosis, psoriatic arthritis, etc.], dermatological disorders associated with PDE-IV enzyme (such as psoriasis and other benign or malignant proliferative skin diseases, atopic dermatitis, and urticaria), neurodegenerative disorders such as Parkinson disease, Alzheimer's disease, acute and chronic multiple sclerosis, cancer cachexia, viral infection, AIDS cachexia, thrombosis, and the like. For therapeutic administration, the compound (I), or its prodrug, or a salt thereof can be administered alone or in the form of a mixture, preferably, with a pharmaceutical vehicle or carrier. The active ingredient of this invention can be used in the form of a pharmaceutical preparation, for example, in solid, semisolid or liquid form, which contains a compound (I), as an active ingredient, in admixture with an organic or inorganic carrier or excipient suitable for external (topical), enteral, intravenous, intramuscular, parenteral or intra-mucous applications. The active ingredient can be formulated, for example, with the conventional non-toxic, pharmaceutically acceptable carriers for ointment, cream, plaster, tablets, pellets, capsules, suppositories, solution (saline, for example), emulsion, suspension (olive oil, for example), aerosols, pills, powders, syrups, injections, troches, cataplasms, aromatic waters, lotions, buccal tablets, sublingual tablets, nasal drops and any other form suitable for use. The carriers which can be used are water, wax, glucose, lactose, gum acacia, gelatin, mannitol, starch paster, magnesium trisilicate, talc, corn starch, keratin, paraffin, colloidal silica, potato starch, urea and other carriers suitable for use in manufacturing preparations, in solid, semisolid, or liquid form, and in addition auxiliary, stabilizing, thickening and coloring agents and perfumes may be used. The active compound is included in a pharmaceutical composition in an effective amount sufficient to produce the desired effect upon the process or condition of the diseases. The active ingredient can be formulated into, for example, preparations for oral application, preparations for injection, preparations for external application, preparations for inhalation, and preparations for application to mucous membranes. Further, the compound of this invention can be used in combination with other therapeutic compounds. In particular, the combinations of the PDE4 inhibiting compound of this invention can be advantageously used in combination with i) Leukotriene receptor antagonists, ii) Leukotriene biosynthesis inhibitors, iii) COX-2 selective inhibitors, iv) statins, v) NSAlDs, vi) M2/M3 antagonists, vii) corticosteroids, viii) Hi (histamine) receptor antagonists, ix) beta 2 adrenoceptor agonist, x) interferon, xi) antiviral drugs for hepatitis C virus (HCV) such as protease inhibitor, helicase inhibitor, polymerase inhibitor, or the like, xii) antiviral drug for hepatitis B virus such as lamivudine, xiii) ursodesoxycholic acid, xiv) glycyrrhizin, xv) human grouth factor (HGF), xvi) aminosalicylic acid such as salazosulfapyridine, mesalazin, or the like, xvii) steroids such as prednisolone farnesylate, xviii) immunosuppressant such as azathioprine, 6-mercaptopurine, tacrolimus, and the like. Mammals which may be treated by the present invention include livestock mammals such as cows, horses, etc., domestic animals such as dogs, cats, rats, etc. and humans, preferably humans. While the dosage of therapeutically effective amount of the compound (I) will vary depending upon the age and condition of each individual patient, an average single dose to a human patient of about 0.01 mg, 0 1 mg, 1 mg, 10 mg, 50 mg, 100 mg, 250 mg, 500 mg, and 1000 mg of the compound (1) may be effective for treating the above-mentioned diseases. In general, amounts between 0.01 mg/body and about 1,000 mg/body may be administered per day. In order to show the utilities of the pyrrolopyridazine derivatives (I) and a pharmaceutically acceptable salt thereof of the present invention, pharmacological test data of the representative compound of the pyrrolopyridazine derivatives (I) are illustrated in the following. 1. Test method: Cultured U937 cells were washed twice and harvested with phosphate-buffered saline (PBS) by cell-scraper. After centrifugation, the cell pellet was suspended in homogenizing buffer (0.5 % deoxycholate [DOC], 5 mM 2-mercaptoetbanol, 1 -iM leupeptin, 100 -M PMSF, 20µm p-tosyl-L-lysine-chloromethyl ketone [TLCK] in PBS). The cell suspension was then sonicated for a couple of minutes and homogenized by a glass-Teflon homogenizer with twenty strokes. The homogenate was centrifuged at 200g for 30 minutes, and the supernatant was further ultra-centrifuged at 100,000 x g for 90 minutes (4°C). The final supernatant was dialyzed against dialysis buffer, which was the same component as homogenizing buffer without DOC. The dialysate of enzyme preparation was stored at -20°C until assay. PDE4, activity was estimated with a Phosphodiesterase [ H]cAMP SPA Enzyme Assay System (Amersham Pharmacia Biotech), using a 96 well Opti-plate. Reactions were initiated by addition of 0.025 -Ci/well of [3H]cAMP to the enzyme mixture containing 50 mM Tris-HCl (pH 7.5), 8.3 mM MgCl2 ,1.7 mM EGTA, and various concentrations of the test compound or vehicle. CI-930 (10µm in final), a specific PDE3, inhibitor, was also added in the reaction mixture. After incubation at 30°C for 15 minutes, 50 µl of SPA beads suspension was added to each well. The well-plate was then shaken for 20 minutes by a plate mixer. Radio-activity in each well was counted by a Top Counter. Test compounds were dissolved in 100% dimethylsulfoxide (DMSO) and diluted into respective concentrations with the final solution containing ] % v/v of DMSO. JC50 values of test compounds for the enzyme activity of PDE4 was determined from regression analysis for log-logit conversion values of percent inhibition in the compound-treated tubes compared to that of the control. Percent inhibition was calculated with the following equation: Inhibition (%) = {1-(C-B)/(A-B)} x 100; in which A, B and C means mean values of radio-activity counts (dpm) of control, blank and the compound-treated tubes, respectively. 2. Test results The following table illustrates the inhibitory activity on PDE-IV of the representative compound of formula (I): (b) Inhibition on TNF-αlpha production in human mononuclear cells l.Test method (1) Human peripheral blood mononuclear cells (PBMCs) preparation Blood (30 ml for each person) was collected from the median cubital vein of healthy volunteer was divided 15 mLeach in heparin containing conical tube and the same volume of RPMI1640 was added to each tube. Diluted blood was then piled up to 20 mLof Ficoll-Paque PLUS (Amersham Pharmacia Biotech) in polystyrene centrifuge tube. After centrifugation at 1 ,600rpm for 30 minutes, cells gathering in the center area of the gradient were collected by capillary and washed with 40 mL of RPMI1640 in several times with centrifugation at 1,200 rpm for 10 minutes. PBMC finally precipitated were suspended in RPMI1640 containing 1% fetal bovine serum and antibiotics. After cell counting, final suspension at 3 x 106cells/mL in culture medium was prepared. (2) TNF-αlpha production from stimulated PBMCs Human PBMCs prepared by the density gradient method using Ficoll-Paque PLUS were suspended in the culture medium mentioned above with the concentration of 3 x 106 cells/mL and 0.5 mL of the suspension was sowed into each well of a 24-well culture plate. Cells were incubated in the CO2 incubator for 24 hours with 0.25 mLof LPS in addition of 0.25 mL of concentrations of drugs or vehicle at the start of the incubation. Final concentration of LPS in the incubation medium was 1 fxg/mL. After 24 hours, the supernatant of each well by centrifugation at 1,700 rpm for 10 minutes was stored at -80°C until assay. TNF-αlpha levels in the medium were measured by ELISA. The IC50 values of drugs on cytokine productions in LPS stimulated PBMC were estimated by the regression analysis for the relative values of cytokine level in the drug-treated wells compared to those of the vehicle-treated ones. Best Mode for carrying out the Invention The following examples are provided to further illustrate details for the preparation of the compounds of the present invention. The examples are not intended to be limitations on the scope of the instant invention in any way, and they should not be so construed. Furthermore, the compounds described in the following examples are not to be construed as forming the only genus that is considered as the invention, and any combination of the compounds or their moieties may itself form a genus. Those skilled in the art will readily understand that known variations of the conditions and processes of the following preparative procedures can be used to prepare these compounds. The starting materials and intermediates are prepared by the application or adaptation of known methods, for example methods as described in the Reference Examples or their obvious chemical equivalents. Preparation 1 To a suspension of 2-pyridinethiol (17 g) in tetrahydrofuran (200 mL) was added triethylamine (15.5 g) in an ice-water bath under N2. To this was added a solution of 4-cyanobenzoyl chloride (25.3 g) in tetrahydrofuran (80 mL) below 10°C over 30 minutes. After 15 minutes, the bath was removed and the mixture was stirred overnight at ambient temperature. The mixture was concentrated in vacuo. The residue was partitioned between chloroform and water. The organic layer was washed with saturated sodium bicarbonate and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue (38 g) was triturated with isopropy] ether to give S-(2-pyridinyl) 4-cyanobenzenecarbothioale (32.5 g) as a pale brown solid. S-(2-Pyridinyl)4-cyanobenzenecarbothioate NMR (CDC13,5): 7.38 (1H, t, J=7Hz), 7.72 (1H, d, J=8Hz), 7.75-7.87 (3H, m), 8.1 J (2H, d, J=8Hz); 8.71 (1H, d, J=2Hz) MS(ESI+):m/z241 (M+H) The following compound(s) was(were) obtained in substantially the same manner as that of Preparation 1. Preparation 2 S-(2-Pyridinyl) 2-chloro-4-pyridinecarbothioate NMR (CDCI3,5): 7.40 (1H, m), 7.65-7.75 (2H, m), 7.75-7.90 (2H, m), 8.62 (1H, d, J=5Hz),8.70(lH,m) Preparation 4 S-(2-Pyridinyl) 3-cyanobenzenecarbothioate NMR (CDCI3, 5): 7.39 (1H, m), 7.66 (1H, t, J=8Hz), 7.72 (1H, t, J=8Hz), 7.83 (1H, m), 7.91 (1H, d, J=8Hz), 8.24 (1H, d, J=8Hz), 8.29 (1H, s), 8.71 (1H, m) MS (ESI+): m/z 241 (M+H) Preparation 5 S-(2-Pyridinyl)3-methoxybenzenecarbothioate NMR (CDCI3, 5): 3.87 (3H, s), 7.16 (1H, m), 7.32-7.44 (2H, m), 7.51 (1H, m), 7.63 (1H, d, J=8Hz), 7.71-7.83 (2H, m), 8.69 (1H, m) Preparation 6 S-(2-Pyridinyl) 4-pyridinecarbothioate NMR (CDCI3, 5): 7.35-7.43 (1H, m), 7.73 (1H, d, J=8Hz), 7.77-7.88 (3H5 m), 8.70 (1H, d, J=7Hz), 8.85 (2H, d, J=8Hz) MS(ESD:m/z217 Preparation 7 S-(2-Pyridinyl) 2-pyrazinecarbothioate NMR (CDCI3, 8): 7.38 (1H, m), 7.71 (1H, d, J=8Hz), 7.82 (1H, m), 8.73 (2H, m), 8.86 (lH,m), 9.17 (lH,s) Preparation 8 S-(2-Pyridinyl) 3-pyridinecarbothioate NMR (CDCI3,8): 7.37 (1H, m), 7.46 (1H, m), 7.73 (1H, m), 7.83 (1H, m), 8.27 (1H, m), 8.68 (1H, m), 8.84 (1H, m), 9.23 (1H, m) Preparation 9 To a solution of 2-ethyl-lH-pyrrole in toluene (120 mL) was added dropwise 1M methylmagnesium bromide in tetrahydrofuran (170 mL) in a dry ice-acetone bath below -60°C over 30 minutes. Then the mixture was stirred in an ice-water bath for 40 minutes. To this reaction mixture was added S-(2-pyridinyl) 4-cyanobenzenecarbothioate (15.2 g) portionwise over 10 minutes in a dryice-acetone bath. After 1.5 hours stirring, saturated ammonium chloride (100 mL) was added therein and the reaction mixture was allowed to ambient temperature. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with IN sodium hydroxide (100 mL) twice, water, and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was triturated with isopropyl ether to give 4-[(5-ethyl-lH-pyrrol-2-yl)carbonyl]benzonitrile (12.7 g) as a pale yellow solid. 4-[(5-Ethyl-lH-pyrrol-2-yl)carbonyl]benzonitrile NMR (CDC13, 8): 1.32 (3H, t, J=8Hz), 2.75 (2H, q, J=8Hz), 6.11 (1H, d, J=5Hz), 6.76 (1H, d, J=5Hz), 7.77 (2H, d, J=8Hz), 7.94 (2H, d, J=8Hz), 9.49 (1H, br s) MS (ESI+): m/z 225 (M+H) The following compound was obtained in substantially the same manner as that of Preparation 9. Preparation 10 (2E)-l-(5-Elhy]-lH-pyrrol-2-y])-3-phenyl-2-propen-l-one NMR(CDC)3,5): 1.31 (3H, t,J=7Hz), 2.73 (2H,q,J=7Hz), 6,10(1 H,m), 7.02 (1H, m), 7.27 (1H, d, J=16Hz), 7.35-7.43 (3H, m), 7.63 (2H, m), 7.79 (1H, d, J=16Hz) MS(ESI+):m/z226(M+H) Preparation 11 To a solution of 4-[(5-elhyl-lH-pyrrol-2-yl)carbonyl]-benzonilrile (12.5 g) in N,N-dimetbylformamide (63 rnL) was added 60% sodium hydride in oil (2.68 g) in an ice-water bath under N2, After 30 minutes, to the mixture was added l-(aminooxy)-2,4- dinitrobenzene (13.3 g). After 2 hours, the mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water (100 mL) 3 times, IN sodium hydroxide (100 mL), and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by flash silica gel chromatography (silica gel, 500 mL) eluted with hexane-chloroform = 1-2,1-5, and 1-10 followed by triturated with isopropyl ether to give 4-[(l-amino-5-ethyl-lH-pyrrol-2-yl)carbonyl]benzonitrile (8.1 g, 60.7%) as an yellow solid. The mixed fraction and the mother layer (7 g) were repurified by flash silica gel chromatography (silica gel, 200 mL) eluted with hexane-chloroform = 2-1 and 1-1 followed by triturated with isopropyl ether to give 4-[(l-amino-5-ethyl-lH-pyrrol-2-yl)carbonyl]benzonitrile (2.0 g, 15%) as a pale yellow solid. 4-[(l-Amino-5-ethyl-lH-pyrrol-2-yl)carbonyl]-benzonitrile NMR (CDC13, 5): 1.29 (3H, t, J=8Hz), 2.77 (2H, q, J=8Hz), 5.75 (2H7 br s), 5.94 (1H, d, J=5Hz), 6.59 (1H, d, J=5Hz), 7.76 (2H, d, J=8Hz), 7.85 (2H, d, J=8Hz) MS (ES1+): m/z 240 (M+H) The following compounds were obtained in substantially the same manner as that of Preparation 11. Preparation 12 (l-Amino-5-ethyl-lH-pyrrol-2-yl)(2-chloro-4-pyridinyl)methanone NMR(CDCl3,5):1.29(3H,t,J=7Hz))2.77(2H,q,J=7Hz),5.71(2H,s),5.96(lH,d, J=4Hz), 6.63 (1H, d, J=4Hz), 7.50 (1H, d, J=4Hz), 7.61 (1H, s), 8.52 (1H, d, J=4Hz) MS: (m/z) 250 (M+H) Preparation .13 3-[(l -Aniino-5-ethyl-l H-pyrrol-2-y])carbonyl]-benzoni(rile NMR (CDC13,6): 1.29 (3H, t, J=7Hz), 2.77 (2H, q, J=7Hz), 5.74 (2H, s), 5.94 (1H, d, J=5Hz), 6.59 (1H, d, J=5Hz), 7.59 (1H, t, J=8Hz), 7.82 (1H, d, J=8Hz), 8.00 (1H, d,J=8Hz),8.06(lH,s) Preparation 14 (2E)-l-(l-Amino-5-ethyl-lH-pyrrol-2-y])-3-phenyl-2-propen-l-one NMR (CDCI3, 5): 1.28 (3H, t, J=7Hz), 2.73 (2H, q, J=7Hz), 5.93 (1H, d, J=5Hz), 6.99 (1H, d, J=5Hz), 7.30 (1H, d, J=16Hz), 7.37-7.43 (3H, m), 7.62 (2H, m), 7.74 (lH,d,J=16Hz) MS (ESI+): m/z 241 (M+H) Preparation 15 (l-Amino-5-ethyl-lH-pyrrol-2-yl)(3-methoxyphenyl)-rnethanone NMR (CDCI3,8): 1.26 (3H, I, J=7Hz), 2.75 (2H, q, J=7Hz), 3.86 (3H, s), 5.79 (2H, s), 5.89 (1H, d, J=4Hz), 6.67 (1H, d, J=4Hz), 7.07 (1H, m), 7.29-7.40 (3H, m) MS (ESI+): m/z 245 Preparation 16 (l-Amino-5-ethyl-lH-pyrrol-2-y])(4-pyridiny])methanone NMR (CDCI3,5): 1.29 (3H, t, J=7Hz), 2.77 (2H, q, J=7Hz), 5.76 (2H, s), 5.94 (1H, d, J=4Hz), 6.63 (1H, d, J=4Hz), 7.58 (2H, d, J=7Hz), 8.75 (2H, d, J=7Hz) MS(ESl+):m/z216 Preparation 17 (l-Amino-5-ethyi-lH-pyrrol-2-yl)(2-pyrazinyl)methanone NMR (CDCI3, 8): 1.29 (3H, t, J=7Hz), 2.77 (2H, q, J=7Hz), 5.79 (2H, s), 5.98 (1H, d, J=4Hz), 7.27 (1H, d, J=4Hz), 8.63 (1H, m), 8.71 (1H, m), 9.17 (1H, m) Preparation 18 (l-Amino-5-ethy]-lH-pyrro]-2-yl)(3-pyridinyl)melhanone NMR (CDC13,5): 1.29 (3H, t, J=7Hz), 2.77 (2H, q, J=7Hz), 5.78 (2H, s), 5.94 (1H, d, J=4Hz), 6.65 (1H, d, J=4Hz), 7.39 (1H, m), 8.06 (1H, m), 8.74 (1H, m), 8.99 (1H, m) Preparation 19 (l-Amino-5-ethyl-lH-pyrrol-2-yl)(5-bromo-3-pyridinyl)-methanone NMR (CDCI3, 5): 1.29 (3H, t, J=7Hz), 2.76 (2H, q, J=7Hz), 5.72 (2H, s), 5.96 (1H, m), 6.65 (1H, m), 8,19 (1H, m), 8.70 (1H, m), 8.89 (1H, m) Preparation 20 To a solution of tert-butyl 3-oxobutanoate (20.0 g) in tetrahydrofuran (200 mL) was added 60% sodium hydride in oil (5.56 g) portionwise over 20 minutes in an ice-water bath under N2. After 40 minutes, to the mixture was added ethyl 5-iodopentanoate (35.6 g) at the temperature. After 15 minutes, the mixture was stirred at ambient temperature. After 1 hour, the reaction mixture was heated at 50°C for 24 hours. The cooled mixture was partitined between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by flash silica gel chromatography (silica gel, 1 L) eluting with hexarie-ethyl acetate = 50-1,20-1,10-1, and 8-1 to give 1-tert-butyl 7-elhyl 2-acetylheptanedioate (27.3 g, 75.4%) as colorless oil. 1-tert-Butyl 7-ethyl 2-acetylheptanedioate NMR (CDCI3, 8): 1.20-138 (5H, m), 1.46 (9H, s), 1.54-1.71 (2H, m), 1.75-1.87 (2H, m), 2.12 (3H, s), 2.30 (2H, t, J=8Hz), 3.30 (12H, t, J=8Hz), 4.11 (2H, q, J=8Hz) The following compounds were obtained in substantially the same manner as that of Preparation 20. Preparation 21 1-tert-Butyl 9-ethyl 2-acetylnonanedioate NMR (CDCI3, 5): 1.23-133 (9H, m), 1.46 (9H, s), 1.55 (2H, m), 1.77 (2H, m), 2.21 (3H, s), 2.28 (2H, t, J=7Hz), 3.27 (1H, I, J=7Hz), 4.12 (2H, q, J=7Hz) MS(ESI+):m/2 315(M+H) Preparation 22 tert-Butyl 2-acetylhexanoate NMR (CDCI3,8): 0.90 (3H, t, J=8Hz), 1.28-1.40 (4H, m), 1.46 (9H, s), 1.73-1.89 (2H, m), 2.22 (3H, s), 330 (1H, t, J=8Hz) Preparation 23 1-tert-Butyl 8-ethyl 2-acetyloctanedioate NMR (CDCI3, 5): 1.21-133 (7H, m), 1.46 (9H, s), 1.54-1.69 (2H, m), 1.74-1.85 (2H, m), 2.21 (3H, s), 2.28 (2H, t, J=8Hz), 3.29 (1H, t, J=8Hz), 4.12 (2H, q, J=8Hz) Preparation 24 To a suspension of magnesium chloride (133 g) in dichloromethane (40 mL) was added 1-tert-butyl 7-ethyl 2-acetylheptanedioate (4.0 g) at ambient temperature under N2. To this mixture was added dropwise pyridine (2.26 mL) in an ice-water bath. Then the mixture was stirred at ambient temperature for 40 minutes. To the reaction mixture was added a solution of 3-cyanobenzoyl chloride (3.01 g) in dichloromethane (6 mL) dropwise over 2 minutes. The reaction mixture was stirred at ambient temperature for 2 hours. To the mixture was added IN hydrogen chloride and ethyl acetate in an ice-water bath. The organic layer was washed with IN hydrogen chloride, water, and brine, dried over magnesium sulfate, and evaporated in vacuo to give a solid. The residue was purified by flash silica gel chromatography (silica gel, 300 mL) eluting with hexane-ethyl acetate = 10-1,8-1,5-1, and 3-1 to give 1-tert-butyl 7-ethyl 2-acetyl-2-(3-cyanobenzoyl)heptanedioate (4.23 g, 72.9%) as colorless oil. 1-tert-Butyl 7-ethyl 2-acetyl-2-(3-cyanobenzoyl)-heptanedioate NMR (CDCI3, 5): 1.25 (3H,t,J=8Hz), 1.28-1.40 (HH,m), 1.63-1.75 (2H,m), 2.19- 2.28 (2H, m), 2.32 (2H, I, J=8Hz), 2.45 (3H, s), 4.11 (2H, q, J=8Hz), 7.56 (1H, t, J=8Hz), 7.80 (2H, dd, J=8,1Hz), 7.95 (2H, dd, J=8,1Hz), 8.06 (1H, br s) MS(ESI+):m/z416(M+H) The following compounds were obtained in substantially the same manner as that of Preparation 24. Preparation 25 Ethyl 2-isobutyryl-4-methyl-3-oxopentanoate NMR (300 MHz, CDC13,5): 1.10-1.23 (12H, m), 1.30-1.43 (3H, m), 2.91-3.10 (2H, m),4.21-4.36(2H,m) Preparation 26 Ethyl 2-(2-chlorobenzoyl)-4-methyl-3-oxopentanoate NMR (300 MHz, CDCI3, 5): 0.79 (3H, t, J=7.5Hz),1.22 (6H, d, J=7.5Hz), 3.36-3.54 (1H, m), 3.88 (2H, q, J=7.5Hz), 7.26-7.44 (4H, m) Preparation 27 Ethyl 4-methyl-2-(2-naphthoyl)-3-oxopentanoate NMR (300 MHz,CDCl3,6): 0.76-1.03 (3H,m), 1.10-1.30 (6H,m), 2.56-2.71 (1/2H, m), 2.88-3.04 (1/6H, m), 3.20-3.35 (1/3H, m), 3.72-4.336 (3H, m), 7.50-7.68 (2+1/3H, m), 7.82-8.01 (3+2/3H, m), 8.09 (1/3H, s), 8.35 (1/2H, s), 8.41 (1/6H, s) MS (ES+):m/e 313.45 Preparation 28 1 -tert-Butyl 7-ethyl 2-acetyl-2-[3-(trifluoromethyl)benzoyl1Heptanedioate NMR (CDCI3, 8): 1.24 (3H, t, J=7Hz), 1.32 (9H, s), 1.36-1.75 (4H, m), 2.15-2.36 (4H, m), 2.45 (3H, s), 4.11 (2H, q, J=7Hz), 7.56 (1H, t, J=8Hz), 7.79 (1H, d, J=8Hz), 7.93 (1H, d, J=8Hz), 8.04 (1H, s) Preparation 29 1-tert-Butyl 7-ethyl 2-acetyl-2-[(5-methyl-3-pyridinyl)carbonyl1Heplanedioate NMR (CDCI3, 8): 1.24 (3H, t, J=7Hz), 1.27-1.42 (2H, m), 1.34 (9H, s), 1.65-1.77 (2H, m), 2.16-2.35 (4H, m), 2.39 (3H, s), 2.43 (3H, s), 4.10 (2H, q, J=7Hz), 7.87 (1 H,s), 8.56 (lH,s), 8.73 (lH,s) MS (ESI+): m/z 406 (M+H) Preparation 30 1-tert-Bulyl 7-ethyl 2-(melhoxyacetyI)-2-[(3-melhoxy- 5isoxazolyl)carbonyl1Heptanedioate NMR (CDCI3, 8): 1.25 (3H, t, J=7Hz), 1.39 (9H, s), 1.35-1.50 (2H, m), 1.64-1.75 (2H, m), 2.15-2.23 (2H, m), 2.32 (2H, t, J=7Hz), 3.40 (3H, s), 4.01 (3H, s), 4.12 (2H, q, J=7Hz), 4.57 (2H, s), 6.54 (1H, s) Preparation 31 1-tert-Butyl 7-ethyl 2-acetyl-2-[3-(l ,3-oxazol-5-yl)benzoyl1Heptanedioate NMR (CDCI3, 8): 1.23 (3H, t, J=7Hz), 1.33 (9H, s), 1.30-1.43 (2H, m), 1.62-1.76 (2H, m), 2.17-2.35 (4H, m), 2.44 (3H, s), 4.09 (2H, q, J=7Hz), 7.42 (1H, s), 7.48 (1H, t, J=8Hz), 7.69 (1H, d, J=8Hz), 7.82 (1H, d, J=8Hz), 7.94 (1H, s), 8.09 (1H, m) Preparation 32 1-tert-Butyl 7-ethyl 2-acetyl-2-(3,4-dichlorobenzoyl)heptanedioate NMR (CDCI3, 5): 1.23 (3H, t, J=7Hz), 1.30-1.43 (2H, m), 1.35 (9H, s), 1.63-1.74 (2H, m), 2.15-2.34 (4H, m), 2.41 (3H, s), 4.10 (2H, q, J=7Hz), 7.48 (1H, d, J=8Hz), 7.56 (1H, dd, J=2,8Hz), 7.88 (1H, d, J=2Hz) Preparation 33 1-tert-Butyl 7-ethyl 2-acetyl-2-[(4-chloro-2-pyridinyl)carbonyl1Heptanedioate NMR (CDCI3, 8): 1.23-1.30 (3H, m), 1.25 (9H, s), 1.40-1.58 (2H, m), 1.65-1.77 (2H, m), 2.10-2.21 (2H, m), 2.35 (2H, t, J=7Hz), 2.61 (3H, s), 4.12 (2H, q, J=7Hz), 7.39 (1H, m), 8.04 (1H, m), 8.43 (1H, d, J=5Hz) MS (ES1+): m/z 426 (M+H) Preparation 34 1-tert-Butyl 7-elhyl 2-[(5-chloro-2-thieny])carbonyl]-2-(methoxyacetyl)heptanec3ioale NMR (CDC13,5): 1.23 (3H, t, J=7Hz), 1.25-1.40 (2H,m), 1.41 (9H,s), 1.62-1.74 (2H, m), 2.26-2.37 (4H, m), 3.37 (3H, s), 4.11 (2H, q, J=7Hz), 4.30 (1H, d, J=17Hz), 4.42 (1H, d, J=17Hz), 6.92 (1H, d, J=4Hz), 7.39 (1H, d, J=4Hz) Preparation 35 1-tert-Butyl 7-ethyl 2-acetyl-2-[(6-methoxy-2-pyrazinyl)carbonyl1Heptanedioale NMR (CDC13, 5): 1.24 (3H, t, J=7Hz), 1.26 (9H, s), 1.38-1.49 (2H, m), 1.66-1.80 (2H, m), 2.14-2.26 (2H, m), 2.33 (2H, t, J=7Hz), 2.57 (3H, s), 3.90 (3H, s), 4.12 (2H, q, J=7Hz), 8.37 (1H, s), 8.83 (1H, s) Preparation 36 1-tert-Butyl 7-ethyl 2-acetyl-2-(l-benzofuran-2-ylcarbonyl)heptanedioate NMR (CDCI3, 8): 1.23 (3H, t, J=7Hz), 1.33 (9H, s), 1.38-1.55 (2H, m), 1.64-1.77 (2H, m), 2.23-2.36 (4H, m), 2.49 (3H, s), 4.08 (2H, q, J=7Hz), 7.32 (1H, m), 7.46 (2H, m), 7.54 (1H, s), 7.71 (1H, d, J=8Hz) Preparation 37 1 -tert-Butyl 7-ethyl 2-acetyl-2-(l -benzothien-2-ylcarbonyl)heptanedioate NMR (CDCI3,5): 1.23 (3H, t, J=7Hz), 1.30-1.45 (2H, m), 1.39 (9H, s), 1.62-1.75 (2H, m), 2.25-2.38 (4H, m), 2.40 (3H, s), 4.10 (2H, q, J=7Hz), 7.36-7.51 (2H, m), 7.76 (lH,s), 7.82-7.88 (2H,m) Preparation 38 1-tert-Butyl 7-ethyl 2-acetyl-2-(l ,3-oxazol-5-ylcarbonyl)heptanedioate NMR(CDC13,6): 1.24 (3H,t, J=7Hz), 1.30-1.45 (2H,m), 1.38 (9H, s), 1.63-1.77 (2H, m), 2.15-2.27 (2H, m), 2.30 (2H, t, J=7Hz), 2.43 (3H, s), 4.10 (2H, q, J=7Hz), 7.80 (1H, s), 7.93 (1H, s) Preparation 39 1-tert-Butyl 7-ethyl 2-acetyl-2-benzoylheptanedioate NMR (CDCI3,5): 1.26 (3H, t, J=7Hz), 1.20-1.40 (2H, m), 1.32 (9H, s), 1.60-1.73 (2H, m), 2.26-2.38 (4H, m), 2.40 (3H, s), 4.12 (2H, q, J=7Hz), 7.36-7.78 (5H, m) Preparation 40 1-tert-Butyl 7-ethyl 2-acetyl-2-(6-quinolinylcarbonyl)heptanedioate NMR (CDC13, 5): 1.21 (3H,t, J=7Hz), 1.30 (9H, s), 1.32-1.47 (2H, m), ] .64-1.77 (2H, m), 2.26-2.38 (4H, m), 2.46 (3H, s), 4.08 (2H, q, J=7Hz), 7.48 (1H, m), 8.04 (1H, dd, J=2 Hz, 8Hz), 8.13 (1H, d, J=8Hz), 8.23 (1H, d, J=8Hz), 8.28 (1H, d, J=2Hz),9.00(lH,m) MS (ESI+): m/z 442 (M+H) Preparation 41 1-tert-Butyl 9-ethyl 2-acetyl-2-[4-({[(benzyloxy)carbonyl]amino}sulfonyl)benzoyl]- nonanedioate NMR (CDC13, 8): 1.23-1.37 (HH,m), 1.60 (9H, s), 2.15-2.31 (4H, m), 2.46 (3H, s), 4.12 (2H, q, J=7Hz), 5.10 (2H, s), 7.26-7.40 (5H, m), 7.65 (1H, s, br), 7.84 (2H, d, J=9Hz),8.06(2H,d,J=9Hz) Preparation 42 1 -tert-Butyl 7-ethyl 2-acetyl-2-(2-chloroisonicotinoyl)heptanedioate NMR (CDCI3, 5): 1.20-1.40 (14H, m), 1.61-1.75 (2H, m), 2.19-2.28 (2H, m), 2.20 (2H, t, J=8Hz), 2.31 (2H, t, J=8Hz), 2.46 (3H, s), 4.11 (2H, q, J=8Hz), 7.41 (1H, dd, J =7,1Hz), 7.55 (1H, d, J=lHz), 8.50 (1H, d, J=7Hz) Preparation 43 1-tert-Butyl 7-ethyl 2-acetyl-2-[3-(methylsulfonyl)benzoyl1Heptanedioate NMR (CDC13, 8): 1.24 (3H, t, J=8Hz), 1.27-1.40 (11H, m), 1.61-1.75 (2H, m), 2.19- 2.35 (4H, m), 2.46 (3H, s), 3.07 (3H, s), 4.10 (2H, q, J=8Hz), 7.65 (1H, t, J=8Hz), 7.99 (1H, dd, J=8,1Hz), 8.09 (2H, br d, J=8Hz), 8.34 (1H, br s) Preparation 44 1-tert-Butyl 7-ethyl 2-acetyl-2-(3-nitrobenzoyl)heptanedioate NMR (CDCI3, 8): 1.30-1.39 (12H, m), 1.61-1.75 (2H, m), 2.19-2.35 (4H, m), 2.47(3H, s), 4.10 (2H, q, J=8Hz), 7.63 (1H, t, J=8Hz), 8.09 (1H, br d, J=8Hz), 8.39 (1H, br d, J=8Hz), 8.60 (1H, br s) Preparation 45 tert-Buty] 2-acetyl-2-(4-cyanobenzoyl)hexanoate NMR (CDC13,5): 0.90 (3H, 1, J=8Hz), 1.20-1.44 (13H, m), 2.15-2.25 (2H, m), 2.45 (3H, s), 7.70 (2H, d, J=8Hz), 7.83 (2H, d, J=8Hz) Preparation 46 1-tert-Butyl 7-ethy] 2-acetyl-2-[(5-bromo-3-pyridinyl)carbonyl1Heptanedioate NMR (CDCI3,5): 1.25 (3H, t, J=7Hz), 1.36 (9H, s), 1.32-1.45 (2H, m), 1.65-1.77 (2H, m), 2.18-2.28 (2H, m), 2.32 (2H, t, J=7Hz), 2.45 (3H, s), 4.11 (2H, q, J=7Hz), 8.20 (1H, m), 8.80 (2H, m) MS: (m/z) 470,472 (M+H) Preparation 47 1 -tert-Butyl 7-ethyl 2-(2-chloroisonicotinoyl)-2-[(methylthio)acetyl1Heptanedioate NMR(CDC13,8): 1.24 (3H, t, J=7Hz), 1.37 (9H,s), 1.23-1.45 (2H,m), 1.63-1.77 (2H, m), 2.05 (3H, s), 2.16-2.28 (2H, m), 2.32 (2H, t, J=7Hz), 3.16 (1H, d, J=17Hz), 4.07 (1H, d, J=17Hz), 4.11 (2H, q, J=7Hz), 7.68 (1H, d, J=5Hz), 7.87 (lH,s),8.49(lH,d,J=5Hz) Preparation 48 Ethyl 2-(4-fluorobenzoyl)-3-oxobutanoate NMR (CDCI3, 8): (mixture of tautomers) 0.97 and 1.02 (3H, t, J=7Hz), 2.07 and 2.42 - (3H, s), 4.01 and 4.13 (2H, q, J=7Hz), 7.06-7.18,7.56, and 7.85 (4H, m) MS (ESI+): m/z 275 (M+H) Preparation 49 1-tert-Butyl 8-ethyl 2-acety]-2-(3-cyanobenzoyl)octanedioate NMR (CDCI3,8): 1.21-1.46 (16H, m), 1.56-1.70 (2H, m), 2.15-2.25 (2H, m), 2.29 (2H, t, J=8Hz), 2.45 (3H, s), 4.12 (2H, q, J=8Hz), 7.56 (1H, t, J=8Hz), 7.80 (2H, dd, J=8, 1 Hz), 7.95 (2H, dd, J=8,1Hz), 8.05 (1H, br s) Preparation 50 1-tert-Butyl 7-ethyl 2-acetyl-2-[(6-chloro-2-pyridinyl)carbonyl1Heplanedioate NMR (CDCI3, 8): 1.25 (3H, t, J=7Hz), 1.27 (9H, s), 1.20-1.78 (4H, m), 2.08 (2H, t, J=7Hz), 2.26-2.40 (2H, m), 2.69 (3H, s), 4.12 (2H, q, J=7Hz), 7.43 (1H, d, J=8Hz), 7.81 (1H, t, J=8Hz), 7.96 (1H, d, J=8Hz) MS (ES1+): m/z 426 Preparation 51 1-tert-Butyl 7-ethyl 2-acetyl-2-(3-methoxybenzoyl)heptanedioate NMR (CDC13, 5): 1.25 (3H, m), 1.34 (9H, s), 1.20-1.92 (4H, m), 2.10-2.38 (4H, m), 2.41 (3H, s), 3.84 (3H, s), 4.04-4.22 (2H, m), 7.08 (1H, br), 7.23-7.40 (3H, m) Preparation 52 1-tert-Butyl 7-ethyl 2-acetyl-2-(3,5-dich]orobenzoyl)heptanedioate NMR (CDC13, 5): 1.24 (3H, t, J=7Hz), 1.26-1.40 (2H, m), 1.36 (9H, s), 1.63-1.76 (2H, m), 2.15-2.36 (4H, m), 2.43 (3H, s), 4.10 (2H, q, J=7Hz), 7.51 (1H, m), 7.60 (2H, m) Preparation S3 1-tert-Butyl 7-ethyl 2-acetyl-2-[(5-chloro-2-thienyl)carbonyl1Heptanedioate NMR (CDCI3, 5): 1.23 (3H, t, J=7Hz), 1.40 (9H, s), 1.30-1.90 (4H, m), 2.20-2.35 (4H, m), 2.38 (3H, s), 4.11 (2H, q, J=7Hz), 6.91 (1H, d, J=4Hz), 7.32 (1H, d, J=4Hz) Preparation 54 1-tert-Butyl 7-ethyl 2-acetyl-2-(3-fluorobenzoyl)heptanedioate NMR (CDCI3,8): 1.23 (3H, t, J=7Hz), 1.35 (9H, s), 1.35-1.45 (2H,m), 1.64-1.74 (2H, m), 2.16-2.35 (4H, m), 2.42 (3H, s), 4.09 (2H, q, J=7Hz), 7.24 (1H, m), 7.35-7.43 (1H, m), 7.46-7.53 (2H, m) Preparation 55 1-tert-Butyl 7-ethyl 2-acety]-2-(3-quino]iny]carbonyl)heptanedioate NMR (CDCI3, 8): 1.22 (3H, t, J=7Hz), 1.33 (9H, s), 1.33-1.53 (2H, m), 1.65-1.78 (2H, m), 2.25-2.43 (4H, m), 2.47 (3H, s), 4.08 (2H, q, J=7Hz), 7.63 (1H, t, J=8Hz), 7.81-7.87 (lH,t,J=8Hz), 7.91 (lH,d, J=8Hz), 8.56 (lH,m), 9.24 (1H, m) MS (ES1+): m/z 442 reparation 56 -tert-Butyl 7-ethyl 2-acetyl-2-isonicotinoylheptanedioate NMR (CDCI3, 8): 1.23 (3H, t, J=7Hz), 1.31 (9H, s), 1.30-1.45 (2H, m), 1.65-1.76 (2H, m), 2.18-2.28 (2H, m), 2.31 (2H, t, J=7Hz), 2.45 (3H, s), 4.10 (2H, q, J=7Hz), 7.52 (2H, d, J=7Hz), 8.75 (2H, d, J=7Hz) preparation 57 L-tert-Butyl 7-ethyl 2-acetyl-2-[(3-methoxy-5-isoxazolyl)carbonyl1Heptanedioate NMR (CDCI3, 8): 1.25 (3H, t, J=7Hz), 1.39 (9H, s), 1.35-1.50 (2H, m), 1.62-1.75 (2H, m), 2.11-2.23 (2H, m), 2.33 (2H, t, J=7Hz), 2.49 (3H, s), 4.01 (3H, s), 4.11 (2H,q,J=7Hz),6.53(lH,s) Preparation 58 1-tert-Butyl 7-ethyl 2-acetyl-2-[(5-methyl-3-isoxazolyl)carbonyl1Heptanedioate NMR (CDCI3, 8): 1.24 (3H,t, J=7Hz), 1.31-1.48 (2H,m), 1.37 (9H, s), 1.63-1.75 (2H, m), 2.18-2.26 (2H, m), 2.31 (2H, t, J=7Hz), 2.47 (3H, s), 2.50 (3H, s), 4.11 (2H,q,J=7Hz),6.38(lH,s) Preparation 59 1-tert-Butyl 7-ethyl 2-(2-chloroisonicotinoyl)-2-(methoxyacetyl)heptanedioate NMR (CDCI3, 8): 1.24 (3H, t, J=7Hz), 1.32-1.45 (2H, m), 1.36 (9H, s), 1.64-1.78 (2H, m), 2.16-2.28 (2H, m), 2.31 (2H, t, J=7Hz), 3.36 (3H, s), 4.11 (2H, q, J=7Hz), 4.25 (1H, d, J=17Hz), 4.39 (1H, d, J=17Hz), 7.39 (1H, d, J=5Hz), 7.54 (lH,s),8.50(lH,d,J=5Hz) MS(ES]+):m/z456 Preparation 60 I-tcrt-Butyl 7-elhyl 2-(methoxyacetyl)-2-(3-methoxybenzoyl)heplaneclioate NMR (CDCJ3,5): 1.22 (3H, t, J=7Hz), 1.25-1.33 (2H, m), 1.34 (9H, s), 1.60-1.75 (2H, m), 2.15-2.40 (4H, m), 3.38 (3H, s), 3.83 (3H, s), 4.08 (2H, q, J=7Hz), 4.39 (1H, d, J=17Hz), 4.55 (1H, d, J=17Hz), 7.07 (1H, m), 7.26-7.34 (3H, m) MS (ESI+): m/z 451 Preparation 61 1 -tert-Butyl 7-ethyl 2-(methoxyacetyl)-2-(6-quinolinylcarbonyl)heptanedioate NMR (CDC13,5): 1.25 (3H, t, J=7Hz), 1.32 (9H, s), 1.30-1.50 (2H, m), 1.65-1.78 (2H, m), 2.26-2.44 (4H, m), 3.38 (3H, s), 4.11 (2H, q, J=7Hz), 4.38 (1H, d, J=17Hz), 4.57 (1H, d, J=17Hz), 7.47 (1H, m), 8.03 (1H, d, J=8Hz), 8.13 (1H, d, J=8Hz), 8.28 (1H, d, J=8Hz), 8.27 (1H, s), 9.01 (1H, m) MS(ESI+):m/z472 Preparation 62 1 -tert-Butyl 7-ethyl 2-(methoxyacetyl)-2-(3-pyridinylcarbonyl)heptanedioate NMR (CDC13, 5): 1.23 (3H, t, J=7Hz), 1.30-1.47 (2H, m), 1.35 (9H, s), 1.63-1.78 (2H, m), 2.22-2.38 (4H, m), 3.37 (3H, s), 4.10 (2H, q, J=7Hz), 4.32 (1H, d, J=17Hz), 4.45 (1H, d, J=17Hz), 7.37 (1H, m), 8.03 (1H, m), 8.73 (1H, m), 8.92 (lH,m) Preparation 63 1 -tert-Butyl 7-ethyl 2-(3-chlorobenzoyl)-2-(methoxyacetyl)heptanedioate NMR (CDCI3, 8): 1.25 (3H, t, J=7Hz), 1.35 (9H, s), 1.20-1.50 (2H, m), 1.60-1.73 (2H, m), 2.25-2.35 (4H, m), 3.37 (3H, s), 4.12 (2H, q, J=7Hz), 4.35 (1H, d, J=17Hz), 4.50 (1H, d, J=17Hz), 7.34 (1H, m), 7.48 (1H, d, J=8Hz), 7.59 (1H, d, J=8Hz),7.73(lH,m) Preparation 64 1-tert-Butyl 7-ethyl 2-acely]-2-(3-methylbenzoyl)heptanedioale NMR (CDCI3, 5): 1.25 (3H, t, J=7Hz), 1.30-1.40 (2H, m), 1.33 (9H, s), 1.60-1.72 (2H, m), 2.10-2.38 (4H, m), 2.21 (3H, s), 2.39 (3H, s), 4.10 (2H, q, J=7Hz), 7.26-7.36 (2H, m), 7.48-7.62 (2H, m) MS (ESI+): m/z 405 Preparation 67 1 -tert-Buly] 7-ethyl 2-(methoxyacetyl)-2-[(5-methyl-3-pyridinyl)carbonyl1Heptanedioale NMR (CDCI3,5): 1.25 (3H, t, J=7Hz), 1.36 (9H, s), 1.30-1.45 (2H, m), 1.62-1.76 (2H, m), 2.20-2.36 (4H, m), 2.40 (3H, s), 3.38 (3H, s), 4.10 (2H, q, J=7Hz), 4.34 (1H, d, J=17Hz), 4.49 (1H, d, J=17Hz), 7.86 (1H, s), 8.56 (1H, s), 8.73 (1H, s) MS(ESl+):m/z436 Preparation 68 1-tert-Butyl 7-ethyl 2-acetyl-2-[(5-bromo-3-pyridinyl)carbonyl1Heptanedioate NMR(CDCl3,8):1.25(3H,t,J=7Hz),1.36(9H,s), 1.32-1.45 (2H,m), 1.65-1.77 (2H, m), 2.18-2.28 (2H, m), 2.32 (2H, t, J=7Hz), 2.45 (3H, s), 4.11 (2H, q, J=7Hz), 8.20 (1H, m), 8.80 (2H, m) MS (ESI+): m/z 470,472 Preparation 69 1-tert-Butyl 7-ethyl 2-[(5-bromo-3-pyridinyl)carbonyl]-2-(methoxyacetyl)heptanedioate NMR (CDCI3,5): 1.24 (3H, t, J=7Hz), 1.30-1.44 (2H, m), 1.37 (9H, s), 1.65-1.77 (2H, m), 2.18-2.36 (4H, m), 3.36 (3H, s), 4.10 (2H, q, J=7Hz), 4.28 (1H, d, J=17Hz), 4.40 (1H, d, J=17Hz), 8.18 (1H, m), 8.80 (2H, m) MS (ESI): m/z 500,502 Preparation 70 1-tert-Butyl 7-ethyl 2-acetyl-2-[(5,6-dichloro-3-pyridiny])carbonyl1Heptanedioate NMR (CDCI3,8): 1.24 (3H, t, J=7Hz), 1.25-1.40 (2H, m), 1.38 (9H, s), 1.65-1.75 (2H, m), 2.18-2.27 (2H, m), 2.28-2.37 (2H, m), 2.44 (3H, s), 4.12 (2H, q, J=7Hz), 8.13 (1H, d, J=2Hz), 8.57 (1H, d, J=2Hz) Preparation 71 1-lert-Buty] 6-elhy] 2-(methoxyacety])-2-[(5-methyl-3-pyridinyl)carbonyl1Hexanedioate NMR (CDCI3, 5): 1.24 (3H, 1, J=7Hz), 1.36 (9H, s), 1.60-1.80 (2H, m), 2.20-2.45 (4H, m), 2.39 (3H, s), 3.38 (3H, s), 4.12 (2H, q, J=7Hz), 4.38 (1H, d, J=18Hz), 4.50 (1H, d, J=18Hz), 7.87 (1H, s), 8.55 (1H, s), 8.73 (1H, s) MS (ESI+): m/z 422 Preparation 72 1-tert-Butyl 5-ethyl 2-(methoxyacetyl)-2-[(5-methy]-3-pyridinyl)carbonyl]pentanedioate NMR (CDCI3, 8): 1.24 (3H, t, J=7Hz), 1.37 (9H, s), 2.23-2.70 (4H, m), 2.39 (3H, s), 3.37 (3H, s), 4.12 (2H, q, J=7Hz), 4.32 (1H, d, J=18Hz), 4.43 (1H, d, J=18Hz), 7.84 (1H, s), 8.55 (1H, s), 8.73 (1H, s) MS (ESI+): m/z 408 Preparation 73 1 -tert-Butyl 6-ethyl 2-acetyl-2-[(5-methyl-3-pyridinyl)carbonyl1Hexanedioate NMR (CDCI3, 6): 1.24 (3H, t, J=7Hz), 1.34 (9H, s), 1.60-1.75 (2H, m), 2.20-2.39 (4H, m), 2.39 (3H, s), 2.46 (3H, s), 4.11 (2H, q, J=7Hz), 7.87 (1H, s), 8.56 (1H, s), 8.73 OH, s) MS (ESI+): m/z 392 Preparation 74 1-tert-Butyl 5-ethyl 2-acetyl-2-[(5-methyl-3-pyridinyl)carbonyl]pentanedioate NMR (CDCI3, 8): 1.24 (3H, t, J=7Hz), 1.36 (9H, s), 2.39 (3H, s), 2.44 (3H, s), 2.35- 2.47 (2H, m), 2.56-2.70 (2H, m), 4.11 (2H, q, J=7Hz), 7.88 (1H, s), 8.56 (1H, s), 8.74 OH, s) MS (ES1+): m/z 378 Preparation 75 1 -tert-Butyl 5-ethyl 2-acelyl-2-[(5-bromo-3-pyridinyl)carbonyl]pentanedioate NMR (CDCI3, 8): 1.24 (3H, t, J=7Hz), 1.37 (9H, s), 2.40 (2H, t, J=7Hz), 2.59 (2H, t, J=7Hz), 2.46 (3H, s), 4.13 (2H, q, J=7Hz), 8.20 (1H, t, J=3Hz), 8.81 (2H, dd, .1=7, 3Hz) Preparation 76 1-lert-Butyl 7-ethyl 2-(3-cyanobenzoyl)-2-(methoxyacetyl)heptanedioate NMR(CDC13,5): 1.20-1.41 (14H,m), 1.60-1.74 (2H, m), 2.27-2.34 (4H,m), 3.37 (83H, s), 4.10 (2H, q, J=8Hz), 4.29 (1H, d, J=16Hz), 4.46 (1H, d, J=16Hz), 7.55 (1H, t, J=8Hz), 7.80 (1H, dd, J=8,1Hz), 7.93 (1H, dd, J=8,1Hz), 8.04 (1H, br s) Preparation 77 1-tert-Butyl 7-ethyl 2-[(acetyloxy)acetyl]-2-[(5-bromo-3- pyridinyl)carbonyl1Heptanedioate NMR (CDC13,5): 1.22-1.28 (5H, m), 1.36 (9H, s), 1.68 (2H, m), 2.14 (3H, s), 2.32 (2H, m), 4.11 (2H, q, J=7Hz), 5.07 (1H, d, J=18Hz), 5.34 (1H, d, J=18Hz), 8.21 (lH,m),8.81(2H,m) Preparation 78 To 1-tert-butyl 7-ethyl 2-acetyl-2-(3-cyanobenzoyl)-heptanedioate (4.2 g) was added trifluoroacetic acid (20 mL) in an ice-water bath. After 30 minutes, the bath was removed and the reaction mixture was stirred at ambient temperature. After 1 hour, the mixture was concentrated. The residue was dissolved in toluene and was evaporated in vacuo to give ethyl 6-(3-cyanobenzoyl)-7-oxooctanoate (3.20 g, 100.4%) as colorless oil. Ethyl 6-(3-cyanobenzoyl)-7-oxooctanoate NMR (CDCI3,5): 1.25 (3H, t, J=8Hz), 1.28-1.40 (2H, m), 1.60-1.74 (2H, m), 1.91- 2.14 (2H, m), 2.17 (3H, s), 2.31 (2H, t, J=8Hz), 4.11 (2H, q, J=8Hz), 4.39 (1H, t, J=8Hz), 7.64 (1H, t, J=8Hz), 7.87 (2H, dd, J=8,1Hz), 8.20 (2H, dd, J=8,1Hz), 8.26(lH,brs) MS(ESr):m/z314(M-H) The following compounds were obtained in substantially the same manner as that of Preparation 78. Preparation 79 Ethyl 7-oxo-6-[3-(trifluoromethyl)benzoyl]octanoate NMR (CDCI3,5): 1.24 (3H, t, J=7Hz), 1.32-1.43 (2H, in), 1.62-1.77 (2H, m), 1.96- 2.17 (2H, m), 2.17 (3H, s), 2.30 (2H, t, J=7Hz), 4.J1 (2H, q, J=7Hz), 4.44 (1H, t, J=7Hz), 7.64 (1H, t, J=8Hz), 7.86 (1H, d, J=8Hz), 8.15 (1H, d, J=8Hz), 8.24 (1H, s) Preparation 80 Ethyl 6-[(5-methyl-3-pyridinyl)carbonyl]-7-oxooctanoate NMR (CDCI3, 5): 1.26 (3H, t, J=7Hz), 1.27-1.44 (2H, m), 1.65-1.75 (2H, m), 1.90- 2.12 (2H, m), 2.17 (3H, s), 2.25-2.34 (2H, m), 2.43 (3H, s), 4.10 (2H, q, J=7Hz), 4.42 (1H, t, J=7Hz), 8.03 (1H, s), 8.63 (1H, s), 8.98 (1H, s) MS (ES1+): m/z 306 (M+H) Preparation 81 Ethyl 8-methoxy-6-[(3-methoxy-5-isoxazolyl)carbonyl]-7-oxooctanoate NMR (CDCI3, 5): 1.25 (3H, t, J=7Hz), 1.34-1.47 (2H, m), 1.65-1.74 (2H, m), 1.83- 2.03 (2H, m), 2.29 (2H, t, J=7Hz), 3.31 (3H, s), 4.05 (5H, s), 4.11 (2H, q, J=7Hz), 4.51 (lH,t,J=7Hz), 6.56 (lH,s) . MS (ES1+): m/z 342 (M+H) Preparation 82 Ethyl 6-[3-(l ,3-oxazol-5-yl)benzoyl]-7-oxooctanoate NMR (CDCI3,5): 1.23 (3H, t, J=7Hz), 1.33-1.46 (2H, m), 1.63-1.77 (2H, m), 1.95- 2.17 (2H, m), 2.17 (3H, s), 2.30 (2H, t, J=7Hz), 4.12 (2H, q, J=7Hz), 4.46 (1H, t, J=7Hz), 7.47 (1H, s), 7.56 (1H, t, J=8Hz), 7.85-7.96 (2H, m), 7.98 (1H, s), 8.27 (lH,m) Preparation 83 Ethyl 6-(3,4-dichlorobenzoyl)-7-oxooctanoate NMR (CDCI3,5): 1.24 (3H, t, J=7Hz), 1.30-1.43 (2H, m), 1.60-1.74 (2H, m), 1.91- 2.14 (2H, m), 2.14 (3H, s), 2.30 (2H, t, J=7Hz), 4.11 (2H, q, J=7Hz), 4.34 (1H, t, J=7Hz), 7.57 (1H, d, J=8Hz), 7.78 (1H, dd, J=2,8Hz), 8.06 (1H, d, J=2Hz) Preparation 84 Ethyl 6-[(4-chloro-2-pyridinyl)carbonyl]-7-oxooctanoate NMR (CDC13, 5): 1.25 (3H, t, J=7Hz), 1.34-] .48 (2H, m), 1.62-1.77 (2H, m), 1.80- 2.10 (2H, m), 2.31 (2H, t, J=7Hz), 2.34 (3H, s), 4.12 (2H, q, J=7Hz), 4.83-4.92 (1H, m), 7.49 (1H, dd, J=2 Hz, 5Hz), 8.04 (1H, d, J=2Hz), 8.57 (1H, d, J=5Hz) MS (ESI+): m/z 326 (M+H) Preparation 85 Ethyl 6- [(5 -chloro-2-thienyl)carbonyl] -8-methoxy-7-oxooctanoate NMR (CDCI3,5): 1.24 (3H, t, J=7Hz), 1321.42 (2H, m), 1.60-1.73 (2H, m), 1.84- 2.06 (2H, m), 2.28 (2H, t, J=7Hz), 3.30 (3H, s), 3.97 (1H, d, J=17Hz), 4.06 (1H, d, J=17Hz), 4.11 (2H, q, J=7Hz), 4.40 (1H, t, J=7Hz), 6.99 (1H, d, J=4Hz), 7.56 (1H, d,J=4Hz) Preparation 86 Ethyl 6-[(6-methoxy-2-pyrazinyl)carbonyl]-7-oxooctanoate NMR (CDCI3,5): 1.25 (3H, t, J=7Hz), 1.34-1.48 (2H, m), 1.60-1.78 (2H, m), 1.88- 2.08 (2H, m), 2.31 (3H, s), 2.32 (2H, t, J=7Hz), 4.01 (3H, s), 4.11 (2H, q, J=7Hz), 4.62 (1H, t, J=7Hz), 8.44 (1H, s), 8.81 (1H, s) MS (ESI+): m/z 323 (M+H) Preparation 87 Ethyl 6-(l-benzofuran-2-ylcarbonyl)-7-oxooctanoate NMR (CDCI3,5): 1.23 (3H, t, J=7Hz), 1.34-1.48 (2H, m), 1.62-1.76 (2H, m), 1.93- 2.19 (2H, m), 2.24 (3H, s), 2.30 (2H, t, J=7Hz), 4.10 (2H, q, J=7Hz), 4.37 (1H, t, J=7Hz), 7.34 (1H, t, J=8Hz), 7.51 (1H, t, J=8Hz), 7.56-7.65 (2H, m), 7.73 (1H, d, 1 J=8Hz) MS (ESI+): m/z 895 (M+H) Preparation 88 Ethyl 6-(l-benzothien-2-ylcarbony])-7-oxooctanoate NMR (CDC13,5): 1.23 (3H, t, J=7Hz), 1.35-1.48 (2H,m), 1.60-1.80 (2H,m), 1.95- 2.17 (2H, m), 2.19 (3H, s), 2.30 (2H, t, J=7Hz), 4.10 (2H, q, J=7Hz), 4.36 (1H, t, J=7Hz), 7.38-7.53 (2H, m), 7.82-7.93 (2H, m), 8.05 (1H, s) Preparation 89 Ethyl 6-(l ,3-oxazol-5-ylcarbonyl)-7-oxooctanoate NMR (CDC13,5): 1.25 (3H, t, J=7Hz), 1.30-1.43 (2H, m), 1.65-1.78 (2H, ra), 1.92- 2.10 (2H, m), 2.21 (3H, s), 2.32 (2H, t, J=7Hz), 4.11 (3H, m), 7.88 (1H, s), 8.05 (lH,s) Preparation 90 Ethyl 6-benzoyl-7-oxooctanoate NMR(CDC13,6): 1.24(3H,t,J=7Hz), 1.29-1.42(2H,m), 1.60-1.75 (2H,m), 1.92- 2.12 (2H, m), 2.14 (3H, s), 2.29 (2H, t, J=7Hz), 4.10 (2H, q, J=7Hz), 4.43 (1H, t, J=7Hz), 7.42-7.53 (2H, m), 7.55-7.64 (1H, m), 7.98 (2H, d, J=8Hz) Preparation 91 Ethyl 7-oxo-6-(6-quinolinylcarbonyl)octanoate NMR (CDC13, 5): 1.23 (3H31, J=7Hz), 1.36-1.48 (2H, m), 1.65-1.78 (2H, m), 2.00- 2.18 (2H, m), 2.18 (3H, s), 2.30 (2H, t, J=7Hz), 4.10 (2H, q, J=7Hz), 4.58 (1H, t, J=8Hz), 7.54 (1H, m), 8.18 (1H, d, J=8Hz), 8.28 (1H, dd, J=2 Hz, 8Hz), 8.32 (1H, d, J=8Hz), 8.51 (1H, d, J=2Hz), 9.05 (1H, m) MS (ESI+): m/z 342 (M+H) Preparation 92 Ethyl 8-[4-({[(benzyloxy)carbonyl]amino}sulfonyl)benzoyl]-9-oxodecanoate NMR (CDC13,5): 1.23-1.37 (9H, m), 1.55-1.68 (11H, s), 2.01 (2H, m), 2.18 (3H, s), 2.29 (2H, t, J=7Hz), 4.12 (2H, q, J=7Hz), 4.39 (1H, t, J=7Hz), 5.11 (2H, s), 7.30-7.49 (5H, m), 7.74 (1H, s, br), 8.04-8.13 (4H, m) MS (ESP): m/z 530 (M-H) Preparation 93 Ethyl 7-(l ,3-oxazol-5-yl)-7-oxoheptanoate NMR (CDCI3,5): 1.25 (3H, t, J=7Hz), 1.41 (2H, m), 1.76 (2H, m), 2.03 (2H, m), 2.31 (2H, m), 3.20 (2H, m), 4.10 (2H, q, J=7Hz), 7.94 (1H, s), 8.10 (1H, s) Preparation 94 Ethyl 6-[3-(methylsulfonyl)benzoyl]-7-oxooctanoate NMR (CDCI3,8): 1.24 (3H, t, J=8Hz), 1.59-1.64 (2H, m), 1.91-2.15 (2H, m), 2.18 (3H, s), 2.30 (2H, t, J=8Hz), 3.11 (3H, s), 4.10 (2H, q, J=8Hz), 4.45 (1H, t, J=8Hz), 7.23 (1H, t, J=8Hz), 8.17 (1H, dd, J=8,1Hz), 8.25 (2H, br d, J=8Hz), 8.53(lH,brs) MS (ESI+): m/z 369 (M+H) Preparation 95 Ethyl 6-(2-chloroisonicotinoyl)-7-oxooctanoate NMR(CDC13,8): 1.25 (3H,t,J=8Hz), 1.30-1.40 (2H,m), 1.60-1.71 (2H,m), 1.90- 2.14 (2H, m), 2.27 (3H, s), 2.25-2.74 (2H, m), 4.11 (2H, q, J=8Hz), 4.32 (1H, t, J=8Hz), 7.15 (1H, dd, J=7,1Hz), 7.76 (1H, d, J=lHz), 8.09 (1H, d, J=7Hz) MS (ES1+): m/z 326 (M+H) Preparation 96 Ethyl 6-(3-nitrobenzoyl)-7-oxooctanoate NMR (CDCI3,5): 1.24 (3H, t, J=8Hz), 1.29-1.41 (2H, m), 1.60-1.74 (2H, m), 1.91- 2.16 (2H, m), 2.19 (3H, s), 2.30 (2H, t, J=8Hz), 4.11 (2H, q, J=8Hz), 4.46 (1H, t, J=8Hz), 7.71 (1H, t, J=8Hz), 8.30 (1H, br d, J=8Hz), 8.45 (4H, br d, J=8Hz), 8.80 (lH,brs) MS (ES1+): m/z 337 (M+H) Preparation 97 4-(2-Acetylhexanoyl)benzonitrile NMR (CDC13,8): 0.90 (3H, t, J=8Hz), 1.18-1.44 (4H, m), 1.90-2.12 (2H, m), 2.17 (3H, s), 4.40 (1H, t, J=8Hz), 7.80 (2H, d, J=8Hz), 8.08 (2H, d, J=8Hz) MS (ESI"): m/z 242 (M-H) Preparation 98 Ethyl 6-[(5-bromo-3-pyridinyl)carbony]]-7-oxooctanoate NMR(CDC13,5): 1.25 (3H, t, J=7Hz), 1.32-1.43 (2H,m), 1.60-1.76 (2H,m), 1.96- 2.15 (2H, m), 2.19 (3H, s), 2.30 (2H, t, J=7Hz), 4.12 (2H, q, J=7Hz), 4.36 (1H, t, J=7Hz), 8.37 (1H, s), 8.87 (1H, br), 9.07 (1H, br) MS: (m/z) 370,372 (M+H) Preparation 99 Ethyl 6-(2-chloroisonicotinoyl)-8-(methylthio)-7-oxooctanoate NMR (CDC13,5): 1.24 (3H, t, J=7Hz), 1.34-1.47 (2H, m), 1.60-1.77 (2H, m), 1.92 (3H, s), 1.93-2.05 (2H, m), 2.30 (2H, t, J=7Hz), 3.19 (1H, d, J=17Hz), 3.26 (1H, d, J=17Hz), 4.11 (2H, q, J=7Hz), 4.68 (1H, t, J=7Hz), 7.72 (1H, d, J=5Hz), 7.86 (1H, s), 8.57 (1H, d, J=5Hz) MS: (m/z) 370 (M-H), 372 (M+H) Preparation 100 Ethyl 7-(3-cyanobenzoyl)-8-oxononanoate NMR (CDCI3,8): 1.21-1.44 (7H, m), 1.55-1.69 (2H, m), 1.89-2.15 (2H, m), 2.17 (3H, s), 2.29 (2H, t, J=8Hz), 4.12 (2H, q, J=8Hz), 4.39 (1H, t, J=8Hz), 7.64 (1H, t, J=8Hz), 7.87 (1H, dd, J=8,1Hz), 8.20 (1H, dd, J=8,1Hz), 8.27 (1H, br s) MS (ESI+): m/z 330 (M+H) Preparation 101 Ethyl 6-[(6-chloro-2-pyridinyl)carbonyl]-7-oxooctanoate NMR (CDCI3, 5): 1.26 (3H, t, J=7Hz), 1.36-1.52 (2H, m), 1.63-1.75 (2H, m), 1.77- 2.06 (2H, m), 2.29 (2H, t, J=7Hz), 2.45 (3H, s), 4.12 (2H, q, J=7Hz), 4.82 (1H, t, J=7Hz), 7.51 (1H, d, J=8Hz), 7.82 (1H, t, J=8Hz), 7.97 (1H, d, J=8Hz) MS (ESI+): m/z 326 Preparation 102 Ethyl 6-(3-methoxybenzoyl)-7-oxooctanoate NMR (CDCI3,5): 1.25 (3H, t, J=7Hz), 1.30-1.43 (2H, m), 1.60-1.77 (2H,m), 1.92- 2.12 (2H, m), 2.15 (3H, s), 2.31 (2H, t, J=7Hz), 3.88 (3H, s), 4.12 (2H, q, J=7Hz), 4.42 (1H, t, J=7Hz), 7.14 (1H, dd, J=2Hz, 8Hz), 7.40 (1H, t, J=8Hz), 7.46-758 (2H,m) MS (ESI+): m/z 321 Preparation 103 Ethyl 6-(3,5-dichlorobenzoyl)-7-oxooctanoate NMR (CDCI3,5): 1.23 (3H, t, J=7Hz), 1.32-1.42 (2H, m), 1.63-1.75 (2H, m), 1.90- 2.12 (2H, m), 2.16 (3H, s), 2.30 (2H, t, J=7Hz), 4.12 (2H, q, J=7Hz), 4.32 (1H, t, J=7Hz), 7.58 (1H, m), 7.82 (2H, m) Preparation 104 Ethyl 6-[(5-chloro-2-thienyl)carbonyl]-7-oxooctanoate NMR (CDCI3,8): 1.24 (3H, t, J=7Hz), 1.30-1.40 (2H, m), 1.62-1.74 (2H, m), 1.90- 2.12 (2H, m), 2.16 (3H, s), 2.29 (2H, t, J=7Hz), 4.13 (2H, q, J=7Hz), 4.14 (1H, m), 6.98 (1H, d, J=4Hz), 158 (1H, d, J=4Hz) Preparation 105 Ethyl 6-(3-fluorobenzoyl)-7-oxooctanoate NMR (CDCI3, 5): 1.24 (3H, t, J=7Hz), 1.28-1.42 (2H, m), 1.60-1.75 (2H, m), 1.90- 2.13 (2H, m), 2.14 (3H, s), 2.29 (2H, t, J=7Hz), 4.11 (2H, q, J=7Hz), 4.37 (1H, t, J=7Hz), 7.26-7.33 (1H, m), 7.43-7.52 (1H, m), 7.63-7.68 (1H, m), 7.76 (1H, d, J=8Hz) MS (ESI+): m/z 309 Preparation 106 Ethyl 7-oxo-6-(3-quinolinylcarbonyl)octanoate NMR (CDCI3,5): 1.23 (3H, t, J=7Hz), 1.35-1.47 (2H, m), 1.63-1.77 (2H, m), 1.98- 2.18 (2H, m), 2.20 (3H, s), 2.31 (2H, t, J=7Hz), 4.10 (2H, q, J=7Hz), 4.55 (1H, t, J=7Hz), 7.66 (1H, t, J=8Hz), 7.87 (1H, t, J=8Hz), 7.97 (1H, d, J=8Hz), 8.18 (1H, d, J=8Hz), 8.78 (1H, d, J=2Hz), 9.43 (1H, d, J=2Hz) MS (ESI+): m/z 342 Preparation 107 Ethyl 6-isonicotinoyl-7-oxooctanoate NMR (CDC13,5): 1.24 (3H, t, J=7Hz), 1.26-1.45 (2H, m), 1.60-1.75 (2H,m), 1.94- - 2.07 (2H, m), 2.17 (3H, s), 2.27-2.35 (2H, m), 4.11 (2H, q, J=7Hz), 4.38 (1H, t, J=7Hz), 7.74 (2H, m), 8.83 (2H, m) Preparation 108 Ethyl 6-[(3-methoxy-5-isoxazolyl)carbonyl]-7-oxooctanoate NMR (CDC13,6): 1.25 (3H, t, J=7Hz), 1.33-1.45 (2H, m), 1.60-1.80 (2H, m), 1.88- 2.05 (2H, m), 2.28 (3H, s), 2.30-2.45 (2H, m), 4.03 (3H, s), 4.11 (2H, q, J=7Hz), 4.33 (1H, t, J=7Hz), 6.56 (1H, s) MS (ESI4): m/z 312 Preparation 109 Ethyl 6-[(5-methyl-3-isoxazolyl)carbonyl]-7-oxooctanoate NMR (CDC13,5): 1.24 (3H, t, J=7Hz), 1.32-1.44 (2H,m), 1.61-1.74 (2H,m), 1.85- 2.07 (2H, m), 2.26-2.38 (2H, m), 2.29 (3H, s), 2.49 (3H, s), 4.11 (2H, q, J=7Hz), 4.64 (lH,m), 6.39 (lH,s) MS (ESI+): m/z 296 Preparation 110 Ethyl 6-(2-chloroisonicotinoyl)-8-methoxy-7-oxooctanoate NMR (CDC13,8): 1.24 (3H, t, J=7Hz), 1.28-1.43 (2H, m), 1.66 (2H, t, J=7Hz), 1.73- 1.86 (1H, m), 1.93-2.07 (1H, m), 2.73 (2H, t, J=7Hz), 3.23 (3H, s), 3.89 (1H, d, J=17Hz), 4.00 (1H, d, J=17Hz), 4.10 (2H, q, J=7Hz), 4.58 (1H, t, J=7Hz), 7.66 (1H, d, J=5Hz), 7.78 (1H, s), 8.60 (1H, d, J=5Hz) MS (ES1+): m/z 356, MS (ESI"): m/z 354 Preparation 111 Ethyl 8-methoxy-6-(3-methoxybenzoyl)-7-oxooctanoate NMR (CDCI3, 5): 1.24 (3H, t, J=7Hz), 1.30-1.43 (2H, m), 1.60-1.73 (2H, m), 1.79- 2.04 (2H, m), 2.28 (2H, t, J=7Hz), 3.27 (3H, s), 3.87 (3H, s), 4.00 (2H, m), 4.12 (2H, q, J=7Hz), 4.66 (1H, t, J=7Hz), 7.13 (1H, m), 7.39 (1H, m), 7.45-7.55 (2H, m) Preparation 112 Ethyl 8-methoxy-7-oxo-6-(6-quinolinylcarbonyl)octanoate NMR (CDCI3,6): 1.24 (3H, t, J=7Hz), 1.34-1.47 (2H, m), 1.60-1.75 (2H, m), 1.86- 2.10 (2H, m), 2.27 (2H, t, J=7Hz), 3.24 (3H, s), 4.02-4.10 (2H, m), 4.12 (2H, q, J=7Hz), 4.83 (1H, t, J=7Hz), 7.48-7.55 (1H, m), 8.16-8.33 (3H, m), 8.49 (1H, m), 9.02 (1H, m) MS (ESI+): m/z 372 Preparation 113 Ethyl 8-methoxy-7-oxo-6-(3-pyridinylcarbonyl)octanoate NMR (CDCI3,5): 1.23 (3H, t, J=7Hz), 1.31-1.45 (2H, m), 1.60-1.73 (2H, m), 1.75- 2.08 (2H, m), 2.28 (2H, t, J=7Hz), 3.24 (3H, s), 3.94 (1H, d, J=17Hz), 4.00 (1H, d, J=17Hz), 4.10 (2H, q, J=7Hz), 4.67 (1H, t, J=7Hz), 7.44 (1H, m), 8.22 (1H, m), 8.81 (1H, d, J=5Hz), 9.18 (1H, m) MS (ESI+): m/z 322 Preparation 114 Ethyl 6-(3-chlorobenzoyl)-8-methoxy-7-oxooctanoate NMR (CDCI3,8): 1.23 (3H, t, J=7Hz), 1.30-1.44 (2H, m), 1.60-1.74 (2H, m), 1.75- 1.92 (1H, m), 1.94-2.10 (1H, m), 2.28 (2H, 1, J=7Hz), 3.25 (3H, s), 3.93 (1H, d, J=17Hz), 4.02 (1H, d, J=17Hz), 4.12 (2H, q, J=7Hz), 4.63 (1H, t, J=7Hz), 7.43 (1H, I, J=8Hz), 7.57 (1H, d, J=8Hz), 7.83 (1H, d, J=8Hz), 7.94 (1H, s) Preparation 115 Ethyl 6-(3-methylbenzoyl)-7-oxooctanoate NMR (CDCI3,6): 1.24 (3H, t, J=7Hz), 1.29-1.42 (2H, m), 1.60-1.73 (2H, m), 1.90- 2.06 (2H, m), 2.13 (3H, s), 2.28 (2H, t, J=7Hz), 2.42 (3H, s), 4.10 (2H, q, J=7Hz), 4.42 (1H, t, J=7Hz), 7.31-7.43 (2H, m), 7.73-7.78 (2H, m) Preparation 118 Ethyl 8-methoxy-6-[(5-methyl-3-pyridinyl)carbonyl]-7-oxooctanoate NMR (CDCI3,5): 1.23 (3H, t, J=7Hz), 1.30-1.47 (2H, m), 1.60-1.74 (2H, m), 1.75- 1.93 (1H, m), 1.93-2.08 (1H, m), 2.26 (2H, t, J=7Hz), 2.43 (3H, s), 3.25 (3H, s), 3.95 (1H, d, J=17Hz), 4.03 (1H, d, J=17Hz), 4.12 (2H, q, J=7Hz), 4.67 (1H, 1, J=7Hz), 8.03 (1H, s), 8.63 (1H, s), 8.98 (1H, s) MS (ES1+): m/z 336 Preparation 119 Ethyl 6-[(5-bromo-3-pyridinyl)carbonyl]-7-oxooctanoate NMR (CDCI3, 8): 1.25 (3H, t, J=7Hz), 1.32-1.43 (2H, m), 1.60-1.76 (2H, m), 1.96- 2.15 (2H, m), 2.19 (3H, s), 2.30 (2H, t, J=7Hz), 4.12 (2H, q, J=7Hz), 4.36 (1H, t, J=7Hz), 8.37 (1H, s), 8.87 (1H, br), 9.07 (1H, br) MS (ES1+): m/z 370,372 Preparation 120 Ethyl 6-[(5-bromo-3-pyridinyl)carbonyl]-8-methoxy-7-oxooctanoate NMR (CDCI3,8): 1.23 (3H, t, J=7Hz), 1.30-1.47 (2H, m), 1.60-1.72 (2H, m), 1.75- 1.93 (1H, m), 1.95-2.08 (1H, m), 2.27 (2H, t, J=7Hz), 3.25 (3H, s), 3.93 (1H, d, J=17Hz), 4.02 (1H, d, J=17Hz), 4.10 (2H, q, J=7Hz), 4.63 (1H, t, J=7Hz), 8.38 (1H, m), 8.88 (1H, m), 9.07 (1H, m) MS (ESI+): m/z 400,402 Preparation 121 Ethyl 6-[(5,6-dichloro-3-pyridinyl)carbonyl]-7-oxooctanoate NMR (CDCI3,8): 1.24 (3H, t, J=7Hz), 1.30-1.43 (2H, m), 1.60-1.77 (2H, m), 1.95- 2.17 (2H, m), 2.19 (3H, s), 2.30 (2H, t, J=7Hz), 4.11 (2H, q, J=7Hz), 4.32 (1H, t, J=7Hz), 8.31 (1H, d, J=2Hz), 8.82 (1H, d, J=2Hz) Preparation 122 Ethyl 7-methoxy-5-[(5-methyl-3-pyridinyl)carbony]]-6-oxoheptanoate NMR (CDGI3,5): 1.23 (3H, t,J=7Hz), 1.60-1.75 (2H,m), 1.78-1.95 (1H, m), 1.95- 2.12 (1H, m), 2.32 (2H, t, J=7Hz), 2.44 (3H, s), 3.25 (3H, s), 3.94 (1H, d, J=18Hz), 4.02 (1H, d, J=18Hz), 4.12 (2H, q, J=7Hz), 4.69 (1H, t, J=7Hz), 8.04 (1H, s), 8.63 (1H, s), 9.00 (1H, s) MS (ES1+): m/z 322 Preparation 123 Ethyl 6-methoxy-4-[(5-methyl-3-pyridinyl)carbonyl]-5-oxohexanoate NMR (CDCI3,6): 1.24 (3H, t, J=7Hz), 2.08-255 (4H, m), 2.44 (3H, s), 3.23 (3H, s), 3.94 (1H, d, J=18Hz), 4.01 (1H, d, J=18Hz), 4.12 (2H, q, J=7Hz), 4.88 (1H, m), 8.12 (1H, s), 8.64 (1H, s), 9.04 (1H, s) MS (ESI+): m/z 308 Preparation 124 Ethyl 5-[(5-methyl-3-pyridinyl)carbonyl]-6-oxoheptanoate NMR (CDCI3, 8): 1.25 (3H, t, J=7Hz), 1.60-1.75 (2H,m), 1.96-2.13 (2H,m), 2.18 (3H, s), 2.36 (2H, t, J=7Hz), 2.43 (3H, s), 4.12 (2H, q, J=7Hz), 4.43 (1H, t, J=7Hz), 8.04 (1H, s), 8.63 (1H, s), 8.97 (1H, s) MS (ESI4): m/z 292 Preparation 125 Ethyl 4-[(5-methyl-3-pyridinyl)carbonyl]-5-oxohexanoate NMR (CDCI3,6): 1.25 (3H, t, J=7Hz), 2.20 (3H, s), 2.26-2.48 (4H, m), 2.43 (3H, s), 4.13 (2H, q, J=7Hz), 4.62 (1H, t, J=7Hz)5 8.08 (1H, s), 8.64 (1H, s), 9.02 (1H, s) MS (ES1+): m/z 278 Preparation 126 Ethyl 4-[(5-bromo-3-pyridinyl)carbonyl]-5-oxohexanoate NMR (CDCI3,8): 1.25 (3H, t, J=7Hz), 2.26 (3H, s), 2.30 (2H, t, J=7Hz), 2.43 (2H, t, J=7Hz), 4.15 (2H, q, J=7Hz), 8.65(1H, s), 8.94 (1H, s), 9.22(1H, s) Preparation 127 Ethyl 6-(3-cyanobenzoyl)-8-methoxy-7-oxooctanoate NMR (CDC13,6): 1.19-1.43 (12H, m), 1.57-1.70 (2H, m), 1.80 (1H, m), 1.99 (1H, m), 2.28 (2H, t, J=8Hz), 3.24 (3H, s), 3.91 (1H, d, J=16Hz), 4.01 (1H, d, J=16Hz), 4.09 (2H, q, J=8Hz), 4.65 (1H, t, J=8Hz), 7.64 (1H, t, J=8Hz), 7.87 (1H, dd, J=8, 1Hz), 8.18 (1H, dd, J=8,1Hz), 8.25 (1H, br s) Preparation 128 Ethyl 8-(acetyloxy)-6-[(5-bromo-3-pyridinyl)carbonyl]-7-oxooctanoate NMR (CDCI3,5): 1.25 (3H, t, J=7Hz), 1.37 (2H, m), 1.67 (2H, m), 1.98-2.06 (5H, m), 2.30 (2H, t, J=7Hz), 4.11 (2H, q, J=7Hz), 4.47 (1H, t, J=7Hz), 4.66 (d, J=17Hz), 4.74 (d, J=17Hz), 8.37 (1H, m), 8.88 (1H, m), 9.06 (1H, m) Preparation 129 To a solution of Meldrum's acid (30 g, 0.208 mol) in dichloromethane (420 mL) was added pyridine (33.7 mL, 0.416 mol) over 3 minutes in an ice-methanol bath under nitrogen atmosphere (-9°C). To this mixture was added dropwise a solution of methoxyacetyl chloride (24.8 g) in dichloromethane (180 mL) over 1 hour period at the temperature. After addition, the reaction mixture was stirred at the temperature for 1 hour and at ambient temperature for 2 hours. The mixture was quenched with IN hydrochoric acid (600 mL). The organic layer was separated and the aqueous layer was extracted with dichloromethane. The combined organic layer was washed with brine, dried over magnesium sulfate, and evaporated in vacuo to give 5-(methoxyacetyl)-2,2-dimethyl-l,3-dioxane-4,6-dione as dark orange oil (38.1 g, 84.7%). 5-(Methoxyacetyl)-2,2-dimethyl-l,3-dioxane-4,6-dione NMR (CDCI3,5): 1.75 (6H, s), 3.53 (3H, s), 4.87 (2H, s) Preparation 130 A solution of 5-(methoxyacetyl)-2,2-dimethyl-l,3-dioxane-4,6-dione (38 g) in tert-butanol (120 mL) and toluene (120 mL) was refluxed for 2 hours under nitrogen atmosphere. The mixture was evaporated in vacuo to give brown oil (32.5 g). The residue was dissolved in hexane-ethyl acetate = 2-1 (200 mL) and was added silica gel (65 g) therein. After stirring for 30 minutes at ambient temperature, the mixture was filtered and washed with hexane-ethyl acetate = 2-1 (200 mL). The filtrate was concentrated in vacuo to give tert-butyl 4-methoxy-3-oxobutanoate as pale yellow oil (30.1 g, 91.0%). tert-Butyl 4-methoxy-3-oxobutanoate NMR(CDC13,5): 1.50 (9H,s),3.41 (2H, s), 3.43 (3H,s), 4.08 (2H,s) Preparation 131 To a mixture of 3-formylbenzoic acid (500 mg) and p-toluenesulfonylmethyl isocyanide (715 mg) in methanol (20 mL) was added potassium carbonate (1.38 g) and the mixture was heated under reflux for 2 hours. After evaporation of solvent, the residue was partitioned between ethyl acetate and water. The aqueous layer was separated and acidified with IN hydrochloric acid. The resulting precipitates were collected and washed with water, methanol and ether to give 3-(l,3-oxazol-5-yl)benzoic acid as a colorless amorphous powder (484 mg). 3-(l,3-OxazoL5-yl)benzoic acid NMR (DMSO-d6,5): 7.63 (1H, t, J=8Hz), 7.84 (1H, s), 7.89-8.02 (2H, m), 8.25 (1H, m), 8.50 (lH,s), 13.22 (lH,br) MS(ESI+):m/zl88(M-H) Preparation 132 A mixture of l-(3-chlorophenyl)-l,3-butanedione (500 mg), 5-(iodomethyl)-2,2-dimethyl-l,3-dioxane (716 mg), and potassium carbonate (351 mg) in dimethylsulfoxide (2.5 mL) was stirred for 14 hours at room temperature and 7 hours at 40°C. The mixture was partitioned between ethyl acetate (20 mL) and water (10 mL). The organic layer was washed with water (10 x 2 mL) and brine, dried over magnesium sulfate, and evaporated to give a brown oil. Flash silica gel column chromatography eluling with ethyl acetate-hexane = 1-10 to 2-5 afforded l-(3-chloroDhenvl)-2-f(2,2-dimethvl-13-dioxan-5- yl)methyl]-l,3-butanedione as an yellow oil (614 mg). 1 -(3-Chlorophenyl)-2-[(2,2-dimethyl-l ,3-dioxan-5-yl)methyl]-l ,3-bulanedione NMR (CDCI3, 5): 1.39 (6H, s), 1.70 (1H, m), 1.91-2.15 (2H, m), 2.16 (3H, s), 3.61 (2H, m), 3.88 (2H, m), 4.46 (1H, t, J=7Hz), 7.44 (1H, t, J=9Hz), 7.57 (1H, m), 7.86 (1H, d, J=9Hz), 7.96 (1H, m) The following compounds were obtained in substantially the same manner as that of Preparation 132. Preparation 133 1-tert-Butyl 7-ethyl 2-(l,3-oxazol-5-ylcarbonyl)heptanedioate NMR (CDC13, 8): 1.26 (3H, t, J=7Hz), 1.32-1.38 (11H, m), 1.67 (2H, m), 1.97 (2H, m), 2.30 (2H, m), 3.86 (1H, t, J=7Hz), 4.11 (2H, q, J=7Hz), 7.86 (1H, s), 8.03 (1H, s) Preparation 134 1-tert-Butyl 7-ethyl 2-[(3,5-dimethyl-4-isoxazolyl)carbonyl1Heptanedioate NMR (CDC13, 5): 1.25 (3H, t, J=7Hz), 1.33-1.41 (11H, m), 1.64 (2H, m), 1.93 (2H, m), 2.30 (2H, m), 2.47 (3H5 s), 2.69 (2H, s), 3.79 (1H, t, J=7Hz), 4.12 (2H, q, J=7Hz) Preparation 135 To a suspensin of magnesium chloride (1.46 g) in tetrahydrofuran (10 ml) was added a solution of ethyl 3-oxo-4-phenylbutanoate (2.0 g) in tetrahydrofuran (10 ml) and the mixture was cooled to 0°C, then pyridine (2.5 ml) was added. The mixture was stirred at 20°C for 30 minutes, then a solution of 4-fluorobenzoyl chloride (2.44 g) in tetrahydrofuran (10 ml) was added at 0°C. After stirring at 20°C for 2 hours, the mixure was partitoned between 0.5N hydrochloric acid and ethyl acetate. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluling with a mixture of ethyl acetate and hexane (1:5) to give ethyl 2-(4-fluorobenzoyl)-3-oxo-4-phenylbutanoate (2.15 g) as an oil. Ethyl 2-(4-fluorobenzoyl)-3-oxo-4-phenylbutanoate (mixture of jautomers, too complicated to be assigned) Preparation 136 A mixture of l-(4-fluorophenyl)butane-l,3-dione Q .0 g), potassium carbonate (3.42 g), and tetrabulylammonium bromide (20 mg) in toluene (10 ml) was refluxed for 3 hours. After cooling to 20°C, ethyl bromoacetate (0.74 ml) was added to the mixture. After being allowed to stand at 20°C overnight, the mixture was partitoned between ethyl acetate and 0.5N hydrochloric acid. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of ethyl acetate and hexane (1:5) to give ethyl 3-(4-fluorobenzoyl)-4-oxopentanoate (964 mg) as an oil. Ethyl 3-(4-fIuorobenzoyl)-4-oxopentanoate NMR (CDC13,8): 1.23 (3H, t, J=7Hz), 2.18 (3H, s), 3.01 (2H, d, J=7Hz), 4.12 (2H, q, J=7Hz), 4.95 (1H, d, J=7Hz), 7.18 (2H, dt, J=2,7Hz), 8.07 (2H, ddd, J=2,5,7Hz) Preparation 137 A mixture of l-(4-fluorophenyl)butane-l,3-dione (1.0 g), potassium carbonate (3.84 g), and tetrabutylammonium bromide (90 mg) in toluene (20 ml) was refluxed for 3 hours, then ethyl 6-bromohexanoate (1.18 ml) was added. After stirring at 100°C for 3 hours, the mixture was partitoned between ethyl acetate and 0.5N hydrochloric acid. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of ethyl acetate and hexane (1:5) to give ethyl 7-(4-fluorobenzoyl)-8-oxononanoate (983 mg) as an oil. Ethyl 7-(4-fluorobenzoyl)-8-oxononanoate NMR (CDC13,8): 1.24 (3H, t, J=7Hz), 1.25-1.45 (4H, m), 155-1.70 (2H, m), 1.90- 2.10 (2H, m), 2.13 (3H, s), 2.27 (2H, t, J=7Hz), 4.11 (2H, q, J=7Hz), 4.37 (1H, t, J=7Hz), 7.16 (2H, t, J=9Hz), 8.02 (2H, dd, J=5,9Hz) Preparation 138 A mixture of pentane-2,4-dione (5.0 g), ethyl 7-bromoheptanoate (11.1 g), potassium carbonate (13.8 g), and cesium carbonate (1.63 g) in a mixture of acetonitrile (150 ml) and dimethylsulfoxide (30 ml) was stirred at 20°C overnight, then pentane-2,4-dione (5 g) was added. After stirring at 20°C overnight, the mixture was partitoned between ethyl acetate and 0.5N hydrochloric acid. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of ethyl acetate and hexane (1:5) to give ethyl 8-acetyl-9-oxodecanoate (5.5 g) as an oil. Ethyl 7-acetyl-8-oxononanoate (mixture of tautomers, too complicated to be assigned) Preparation 139 To a mixture of ethyl 7-acetyl-8-oxononanoate (4.0 g) and magnesium chloride (1.27 g) in dichloromethane (70 ml) was added pyridine (2.15 ml) at 0°C. The mixture was stirred at 20°C for 1 hour, then a solution of 4-cyanobenzoyI chloride (2.87 g) in dichloromethane (10 ml) was added. After stirring for 3 hours at 20°C, the mixture was partitioned between ether and IN hydrochloric acid. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of ethyl acetate and hexane (1:5) to give ethyl 7-acetyl-7-(4-cyanobenzoyl)-8-oxononanoate (3.52 g) as an oil. 1-tert-Butyl 8-ethyl 2-acetyl-2-(4-cyanobenzoyl)octanedioate NMR(CDCl3,8):1.24(3H,t,J=7Hz),1.25-1.45(4H,m),130(9H,s)>1.55-1.70 (2H, m), 2.20 (2H, t, J=7Hz), 2.28 (2H, t, J=7Hz), 2.44 (3H, s), 4.12 (2H5 q, J=7Hz), 7.72 (2H, t, J=9Hz), 7.83 (2H, d, J=9Hz) Preparation 140 Ethyl 7-acetyl-7-(4-cyanobenzoyl)-8-oxononanoate (3.5 g) was dissolved in trifluoroacetic acid (12.6 ml) and the mixture was stirred at 20°C for 15 minutes. The mixture was partitoned between ethyl acetate and water. The organic layer was separated, washed with water, aqueous sodium bicarbonate and brine, dried over MgSC>4 (magnesium sulfate), and evaporated to give ethyl 7-(4-cyanobenzoyl)-8-oxononanoate (2.25 g) as an oil. Ethyl 7-(4-cyanobenzoyl)-8-oxononanoate NMR (CDCJ3, 5): 1.25 (3H, t, J=7Hz), 1.25-1.45 (4H, m), 1.55-1.70 (2H, m), 1.80- 2.10 (2H, m), 2.16 (3H, s), 2.28 (2H, t, J=7Hz), 4.12 (2H, q, J=7Hz), 4.40 (1H, I, J=7Hz), 7.80 (2H, t, J=9Hz), 8.07 (2H, d, J=9Hz) Preparation 141 A mixture of methyl 4-(arninosulfonyl)benzoate (5.10 g) and potassium carbonate (6.55 g) in dimethoxyethane (50 mL) was refluxed for 5 minutes. After cooling the mixture, a solution of benzyl chloridocarbonate (5.25 g) in dimethoxyethane (30 mL), and the resulting mixture was refluxed for 1 hour. The reaction was quenched by adding IN hydrochloric acid (100 mL). The mixture was extracted with ethyl acetate (200 mL), and the organic layer was washed with brine, dried over magnesium sulfate, and evaporated to give a pale yellow oil, which was solidified upon standing. The solid was triturated in diisopropyl ether (30 mL) to give methyl 4-({[(benzyloxy)carbonyl]amino}sulfonyl)benzoate as a white powder (3.38 g). Methyl 4-({[(benzyloxy)carbonyl]amino}sulfonyl)benzoate NMR (CDC13, 5): 3.98 (3H, s), 5.10 (2H, s), 7.22 (2H, m), 7.34 (3H, m), 7.64 (1H, s, br), 8.08 (2H, d, J=9Hz), 8.16 (2H, d, J=9Hz) Preparation 142 A suspension of methyl 4-({[(benzyloxy)carbonyl]amino}-sulfonyl)benzoate (3.38 g) and 85% pottasium hydroxide (1.28 g) in methanol (40 mL) was stirred for 35 minutes. Methanol was evaporated off, and to the mixture was added IN hydrochloric acid (20 mL). A white crystal was formed, which was collected by filtration and washed with water and diisopropyl ether, and dried under vacuum. 4-({[(Benzyloxy)carbonyl]amino}sulfonyl)benzoic acid was obtained as a white crystal (2.92 g). 4-({[(Benzyloxy)carbonyl]amino}sulfonyl)benzoic acid NMR (DMSO-d6,8): 5.06 (2H, s), 7.25 (2H, m), 7.33 (3H, m), 8.00 (2H, d, J=9Hz), 8.15(2H,d,J=9Hz) MS(ESI"):m/z334(M-H) Preparation 143 To a suspension of S-(2-pyridinyl) 3-cyanobenzenecarbothioate (2.40 g) in toluene (10 mL) was added titanium chloride (1.99 g) under an ice-methanol bath over 5 minutes (-7 to -2°C). After stirring for 10 minutes, a solution of 2-ethyl-lH-pyrrole (1.00 g) in toluene (10 mL) was added over 5 minutes (-4 to 0°C). The resulting heterogeneous mixture was stirred for 1.5 hours at room temperature. Ethyl acetate (20 mL) and water (20 mL) were added, and the mixture was filtered through celite. The filtrate was diluted with ethyl acetate (80 mL) and water (30 mL), and organic extract was washed with water (30 mL), IN sodium hydroxide (50 mL), and brine (50 mL), dried over magnesium sulfate, and evaporated to give a dark colored crystal (2.46 g). The crystal was triturated in diisopropyl ether (10 mL) to give 3-[(5-ethyl-lH-pyrrol-2-yl)carbonyl]benzonitrile as a brown crystal (1.57 g, 70.1%). 3-[(5-Ethyl-lH-pyrrol-2-yl)carbonyl]benzonitrile NMR (CDC13,5): 1.33 (3H, t, J=7Hz), 2.75 (2H, q, J=7Hz), 6.12 (1H, m), 6.78 (1H, m), 7.60 (1H, t, J=8Hz), 7.82 (1H, d, J=8Hz), 8.07 (1H, d, J=8Hz), 8.14 (1H, s), 9.50(lH,s,br) Preparation 144 To a suspension of magnesium chloride (3.01 g) in tetrahydrofuran (30 mL) was added tert-butyl 3-oxobutanoate (5.00 g). The mixture was cooled under an ice-bath. Then, pyridine (5.00 g) was added over 15 minutes. After stirring for 1 hour at room temperature, the resulting mixture was cooled under the ice-bath. A solution of 2-chlorobenzoyl chloride (4.98 g) in tetrahydrofuran (30 mL) was added over 15 minutes. The mixture was stirred for 1 hour at room temperature. The reaction was quenched by adding IN hydrochloric acid (65 mL). The mixture was filtered, and the solvent was evaporated off. The residue was extracted with ethyl acetate (150 mL). The extract was washed with water (100 mL), saturated sodium bicarbonate (100 mL), and brine, dried over magnesium sulfate, and evaporated lo give tert-butyl 2-(3-chlorobenzoyl)-3- oxobutanoate as an yellow oil (8.82 g). terl-Butyl 2-(3-chlorobenzoyl)-3-oxobutanoate NMR (CDCI3, 5): mixture of tautomers: 1.20 and 1.27 (9H, s), 2.16 and 2.44 (3H, s), 7.33-7.71 (4H,m), 13.66 (lH,s) Preparation 145 A solution of tert-butyl 2-(3-chlorobenzoyl)-3-oxobutanoate (8.82 g) in trifluoroacetic acid (40 mL) was stirred for 1 hour under an ice-bath. The volatile was removed in vacuo, and the residue was partitioned between ethyl acetate (150 mL) and saturated sodium bicarbonate. The organic layer was washed with brine, dried over magnesium sulfate, and evaporated to give l-(3-chlorophenyl)-l,3-butanedione as a pale orange crystal (5.33 g). l-(3-Chlorophenyl)-l ,3-butanedione NMR (CDCI3, 5): 2.21 (3H, s), 6.14 (1H, s), 7.38 (1H, t, J=9Hz), 7.48 (1H, d, J=9Hz), 7.75 (1H, d, J=9Hz), 7.85 (1H, s) Preparation 146 To a mixture of 2-(trimethylsilyl)ethanol (20.5 g) and pyridine (18.7 g) in dichloromethane (40 mL) was added a solution of ethanedioyl dichloride (10.0 g) in dichloromethane (20 mL) over 30 minutes under an ice-bath (6 to 20°C). The bath was removed, and the mixture was stirred for 0.5 hour. The mixture was filtered, and the filtrate was partitioned between ethyl acetate (200 mL) and IN hydrochloric acid (200 mL). The organic layer was washed with saturated sodium bicarbonate and brine, dried over magnesium sulfate, and evaporated to give bis[2-(trimethylsilyl)ethyl] oxalate as a pale yellow oil (25.1 g). bis[2-(Trimethylsilyl)ethyl]oxalate NMR (CDCI3, 6): 0.08 (18H, s), 1.12 (4H, m), 4.38 (4H, m) Preparation 147 To a suspension of dimethyl sulfone (7.00 g) in diethyl ether (50 mL) was added potassium tert-butoxide (8.76 g). To the resulting mixture was added bis[2-(trimetbylsilyl)- ethyljoxalate (23.8 g). The resulting mixture was stirred for 36 hours at room temperature. The mixture was partitioned between ethyl acetate (100 mL) and IN hydrochloric acid (50 mL). The organic layer was washed with brine, dried over magnesium sufate, and evaporated to give a dark orange oil. Flash silica gel column chromatography eluting with ethyl acetate-hexane = 1-25 to 8-5 afforded 2-(trimethylsilyl)ethyl 3-(methylsulfonyl)-2-oxopropanoate as a pale brown oil (8.37 g). 2-(Trimethylsilyl)ethyl 3-(methylsulfonyl)-2-oxopropanoate NMR (CDC13,5): 0.08 (9H, s), 1.14 (2H, m), 3.11 (3H, s), 4.43 (4H, m), 4.56 (2H, s) MS (ESI): m/z 265 (M-H) Preparation 148 A mixture of 4-oxo-4-phenylbutanoic acid (5.00 g), ethanol (2.59 g), l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (6.46 g), and 4-(dimethylamino)pyridine (171 mg) in N,N-dimethylformamide (25 mL) was stirred for 1.5 hours at room temperature. The mixture was partitioned between ethyl acetate (100 mL) and IN hydrochloric acid (75 mL), and the organic layer was washed with water (75 x 3 mL), saturated sodium bicarbonate (75 mL), and brine (75 mL), dried over magnesium sulfate, and evaporated to give ethyl 4-oxo-4-phenylbutanoate as a colorless oil (4.19 g). Ethyl 4-oxo-4-phenylbutanoate NMR (CDCI3,5): 1.27 (3H, t, J=7Hz), 2.76 (2H, t, J=7Hz), 3.32 (2H, t, J=7Hz), 4.16 (2H, q, J=7Hz), 7.47 (2H, t, J=9Hz), 7.55 (1H, d, J=9Hz), 7.98 (2H, d, J=9Hz) MS (ESI+): Hi'2 207 (M+H) The following compound was obtained in substantially the same manner as thai of Preparation 148. Preparation 149 Elhy] 5-oxo-5-phenylpentanoate NMR (CDCI3, 5): 1.26 (3H, t, J=7Hz), 2.08 (2H, m), 2.44 (2H, t, J=7Hz), 3.06 (2H, t, J=7Hz), 4.14 (2H, q, J=7Hz), 7.46 (2H, t, J-9Hz), 7.56 (1H, d, J=9Hz), 7.97 (2H, d,J=9Hz) MS(ESI+):m/2 221(M+H) Preparation 150 A mixture of 2-benzoylcyclohexanone (1.00 g), sodium ethoxide (404 mg) in ethanol (5 mL) was stirred for 3.5 hours at room temperature. The reaction was quenched by adding IN hydrochloric acid (1 mL). The solvent was evaporated off, and the residue was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over magnesium sulfate, and evaporated to give ethyl 7-oxo-7-phenylheptanoate as a brown oil (133 g). Ethyl 7-oxo-7-phenylheptanoate NMR (CDC13,6): 1.25 (3H, t, J=7Hz), 1.42 (2H, m), 1.63-1.81 (4H, m), 2.32 (2H, t, J=7Hz), 2.98 (2H, t, J=7Hz), 4.12 (2H, q, J=7Hz), 7.47 (2H, t, J=9Hz), 7.54 (1H, d, J=7Hz), 7.95 (2H, d, J=9Hz) Preparation 151 To a solution of ethyl 7-chloro-7-oxoheptanoate (1.31 g) in dichloromethane (25 mL) was added a solution of 2-(trirnethylsilyl)-l,3-thiazole (500 mg) in dichloromethane (5 mL) under nitrogen. After stirring for 3 hours, the reaction was quenched by adding saturated sodium bicarbonate (5 mL). The mixture was partitioned between ethyl acetate (30 mL) and saturated sodium bicarbonate (30 mL), and the organic layer was washed with brine, dried over magnesium sulfate, and evaporated to give a colorless oil. Flash silica gel column chromatography eluting with ethyl acetate-hexane = 1-10 to 2-5 afforded ethyl 7-oxo-7-(l,3-thiazol-2-yl)heptanoate as a colorless oil (778 mg). Ethyl 7-oxo-7-(l ,3-thiazol-2-yl)heptanoate NMR (CDC13, 8): 1.25 (3H, t, J=7Hz), 1.44 (2H, m), 1.64-1.85 (4H, m), 2.32 (2H, t, J=7Hz), 3.17 (2H, 1, J=7Hz), 4.12 (2H, q, J=7Hz), 7.66 (1H, d, J=3Hz), 8.00 (1H, d,J=3Hz) MS(ESI+):m/z256(M+H) Preparation 152 To a solution of 7-methoxy-7-oxoheptanoic acid (1.00 g) in dichloromethane (10 mL) was added a solution of trifluoroacetic anhydride (1.33 g) in dichloromethane (2 mL). After stirring for 0.5 hour, a solution of 1-methyl-lH-pyrrole (1.49 g) in dichloromethane (2 mL) was added. The mixture was stirred for 2 hours 40 minutes at room temperature and 2 hours at 35°C. The mixture was partitioned between ethyl acetate and saturated sodium bicarbonate. The organic layer was washed with brine, dried over magnesium sulfate, and evaporated to give a brmown oil. Flash silica gel column chromatography eluting with ethyl acetate-hexane = 1-20 to 4-5 afforded methyl 7-(l-methyl-lH-pyrrol-2-yl)-7-oxoheptanoate as a colorless oil (615 mg). Methyl 7-(l-methyl-lH-pyrrol-2-yl)-7-oxoheptanoate NMR (CDC13> 5): 1.34 (2H, m), 1.61-1.77 (4H, m), 2.32 (2H, t, J=7Hz), 2.77 (2H, t, J=7Hz), 3.66 (3H, s), 3.94 (3H, s), 6.13 (1H, m), 6.79 (1H, m), 6.93 (1H, m) MS (ES1+): m/z 238 (M+H) Preparation 153 To a suspension of 4-({[(benzyloxy)carbonyl]amino}-sulfonyl)benzoic acid (2.90 g) in dichloromethane (30 mL) was added N,N-dimethylformamide (19.0 mg) and followed by oxalyl chloride (1.15 g) under an ice-bath. The mixture was stirred for 0.5 hour at room temperature and refluxed for 1 hour. The resulting mixture was refluxed further for 5 minutes after adding oxalyl chloride (439 mg). The volatile was evaporated off to give a white solid. The solid was triturated in diisopropyl ether to give benzyl [4-(chlorocarbonyl)phenyl]sulfonylcarbamate as a white powder (2.40 g), which was used for the next reaction without further purification. Benzyl [4-(chlorocarbonyI)phenyl]sulfonylcarbamate Preparation 154 To a solution of lerl-butyl 4-(methylthio)-3-oxobutanoate (5.00 g) and potassium carbonate (3.72 g) in dimethylformamide (25 mL) was added ethyl 5-iodopentanoate (6.89 g) and the mixture was stirred at ambient temperature for 15 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of bexane and ethyl acetate (20:1 -10:1) to give 1-tert-butyl 7-ethyl 2-[(methylthio)acetyl1Heptanedioate as colorless oil (5.88 g), 1-tert-butyl 7-ethyl 2-[(methylthio)acetyl1Heptanedioate NMR(CDC13,5): 1.25 (3H,t, J=7Hz), 130-1.42 (2H,m), 1.45 (9H,s), 1.63-1.74 (2H, m), 1.81-1.93 (2H, m), 2.05 (3H, s), 2.30 (2H, t, J=7Hz), 3.23 (1H, d, ]=17Hz), 3.38 (1H, d, J=17Hz), 3.74 (1H, t, J=7Hz), 4.11 (2H, q, J=7Hz) Preparation 155 To a suspension of hydroxylamine hydrochloride (29.4 g) in dichloromethane (200 mL) was added diisopropylethylamine (54.6 g) over 3 minutes in a methanol-ice bath under a nitrogen atmosphere. A white precipitate was formed upon the addition. After stirring for 1 hour under the bath, a solution of diphenylphosphinic chloride (20.0 g) in dichloromethane (20 mL) was added over 60 minutes. A white crystal was formed upon the addition. The mixture was warmed to 0°C over 1 hour with stirring. The reaction was quenched by adding water (200 mL) over 3 minutes. After stirring the mixture for 0.5 hour, the crystal was collected by filtration. The crystal was washed with water (50 x 3 mL) followed by diisopropyl ether (50 x 3 mL). The collected crystal was dried overnight in the air and 3 hours under a reduced pressure with slight warming (4°C) to give a crude product. The crude product was triturated in EtOH (ethanol) to give (aminooxy)(diphenyl)phosphine oxide as a white crystal (15.3 g). (Aminooxy)(dipheny])phosphine oxide NMR (CDC13,5): 7.54-7.58 (6H, m), 7.74-7.83 (4H, m), 8.20-8.33 (2H, m) Preparation 156 To a solution of l-(lH-pyrrol-2-yl)ethanone (5.00 g) in telrahydrofuran (100 mL) was added potassium tert-butoxide (6.17 g) in a water bath under a nitrogen atmosphere. After stirring for 1 hour, (aminooxy)(diphenyl)phosphine oxide (12.8 g) was added over 2 hours. After stirring for 2 hours at room temperature, water (4 mL) was added over 3 minutes to give a clear solution. The solvent was evaporated off, and the residue was partitioned between ethyl acetate (50 mL) and water (50 mL). The aqueous layer was extracted with ethyl acetate (25 x 5 mL), and the combined organic extract was washed with brine, dried over anhydrous magnesium sulfate, and evaporated to give a brown oil (6.01 g). The oil was dissolved in diisopropyl ether (30 mL), and to the solution was added hexane (15 mL) to afford a pale yellow crystal. After stirring for 1 hour, the crystal was removed by filtration. The filtrate was evaporated to give a brown oil (5.69 g). The oil was dissolved in ethyl acetate (45.5 mL), the solution was cooled under an ice-bath. To the cooled solution was added 4N hydrogen chloride in ethyl acetate (11.5 mL) over 15 minutes to afford a pale brown precipitate. After stirring the mixture for 0.5 hour under the bath, the precipitate was collected by filtration and washed with ethyl acetate (5x3 mL) to give a pale brown powder (5.33 g). The powder was suspended in ethyl acetate (37 mL) and warmed to 3°C. The suspension was stirred for 1 hour at room temperature. The powder was collected by filtration and washed with ethyl acetate (5x3 mL) to give l-(l-amino-lH-pyrrol-2-yl)ethanone hydrochloride as a pale brown powder (5.25 g). l-(l-Amino-lH-pyrrol-2-yl)ethanohe hydrochloride NMR (CDC13,5): 2.37 (3H, s), 5.22 (2H, s, br), 6.07 (1H, m), 6.99 (1H, m), 7.15 (1H, m) Preparation 157 Under a nitrogen atmosphere, hydrazine monohydrate (530 g) was added to ethanol (1.7 L) over 55 minutes. To the mixture was added l-(l-amino-lH-pyrrol-2-yl)ethanone hydrochloride (170 g) over 20 minutes. The mixture was stirred for 10 minutes at room temperature and heated to refluxing temperature over 55 minutes, and refluxed for 15 minutes. After cooling the mixture under a water bath, water (1.7 L) was added to the mixture (30 to 31°C). Ethanol was evaporated off, and the resulting mixture was extracted with chloroform (0.85 x 4 mL). The combined organic extract was washed with brine (1.3 L). The brine was extracted with chloroform (0.85 L). The combined rganic extract was dried over anhydrous magnesium sulfate, and evaporated to give lE)-l-(l-amino-lH-pyrrol-2-yl)ethanone hydrazone as a brown crystal (112 g). lE)"l-(l-Amino-lH-pyrrol-2-yl)ethanone hydrazone NMR (CDC13,5): 2.10 (3H,s), 5.11 (2H,s,br), 5.83 (2H,s,br), 5.98 (lH,m), 6.25 (lH,m),6.79(lH,m) MS (ESI+): m/z 139 (M+H) -reparation 158 To a suspension of (lE)-l-(l-amino-lH-pyrrol-2-yl)ethanone hydrazone (110 g) n toluene (1.1 L) was added potassium tert-butoxide (93.8 g) over 5 minutes under a litrogen atmosphere, and the mixture was heated to refluxing temperature over 45 ninutes. After refluxing for 15 minutes, the mixture was cooled to room temperature and partitioned between ethyl acetate (1.1 L) and water (1.1 L). The aqueous layer was extracted with ethyl acetate (1.1 L) again. The combined organic extract was was washed with brine (1.1 L), and the brine was extracted with ethyl acetate (0.5 L). All the organic layer was combined, dried over anhydrous magnesium sulfate, and evaporated to give 2-sthyl-lH-pyrrol-1-amine as a brown oil (94.4 g). 2-Ethyl-lH-pyrrol-l-amine NMR (CDCI3,8): 1.26 (3H, t, J=7Hz), 21.62 (2H, q, J=7Hz), 4.53 (2H, s, br), 5.80 (1H, m), 5.99 (1H, m), 6.67 (1H, m) Preparation 159 To a suspension of tert-butyl 4-methoxy-3-oxobutanoate (3.09 g) and potassium carbonate (2.50 g) in dimethylformamide (20 mL) was added ethyl 5-iodopentanoate (4.62 g) and the mixture was stirred at ambient temperature for 15 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and ethyl acetate (20:1 - 5:1) to give 1-tert-butyl 7-ethyl 2-(methoxyacetyl)heptanedioate as colorless oil (4.33 g). 1-tert-Buly] 7-ethyl 2-(melhoxyacetyl)heptanedioate NMR(CDC13,5): 1.25 (3H,t,J=7Hz), 1.30-1.44 (2H, m), 1.45 (9H,s), 1.60-1.73 (2H, m), 1.80-1.93 (2H, m), 2.29 (2H, t, J=7Hz), 3.41 (3H, s), 3.47 (1H, t, J=7Hz), 4.02 (4H,m) MS:(m/z)317(M+H) The following compounds were obtained in substantially the same manner as that of Preparation 159. Preparation 160 1-tert-Butyl 6-ethyl 2-(methoxyacetyl)hexanedioate NMR(CDC13, 8): 1.25 (3H,t, J=7Hz), 1.46 (9H,s), 1.52-1.73 (2H,m), 1.82-1.94 (2H, m), 2.33 (2H, t, J=7Hz), 3.42 (3H, s), 3.50 (1H, t, J=7Hz), 4.10 (2H, s), 4.12 (2H,q,J=7Hz) Preparation 161 1-tert-Buty] 5-ethyl 2-(methoxyacetyl)pentanedioate NMR (CDC13, 8): 1.26 (3H, t, J=7Hz), 1.47 (9H, s), 2.10-2.25 (2H, m), 2.37 (2H51, J=7Hz), 3.42 (3H, s), 3.62 (1H, t, J=7Hz), 4.12 (2H, s), 4.13 (2H, q, J=7Hz) Preparation 162 1-tert-Butyl 6-ethyl 2-acetylhexanedioate NMR (CDCI3, 8): 1.26 (3H, t, J=7Hz), 1.47 (9H, s), 1.57-1.75 (2H, m), 1.79-1.93 (2H, m), 2.23 (3H, s), 2.33 (2H, t, J=7Hz), 3.33 (1H, t, J=7Hz), 4.12 (2H, q, J=7Hz) MS (ES1+): m/z 273 Preparation 163 1-tert-Butyl 5-ethyl 2-acetylpentanedioate NMR (CDCI3,8): 1.26 (3H, t, J=7Hz), 1.47 (9H, s), 2.08-2.22 (2H, m), 2.24 (3H, s), 2.33-2.42 (2H, m), 3.45 (1H, t, J=7Hz), 4.13 (2H, q, J=7Hz) Preparation 164 To a solution of 2-ethyl-lH-pyrrole (7.00 g) in tetrahydrpfuran (14 mL) was added 0.93 M ethyl magnesium bromide (198 mL) under an ice-bath. The mixture was stirred for 1 hour at room temperature. Then the resulting solution was added to a suspension of 5-bromonicotinoyl chloride (22.3 g) in tetrahydrofuran (110 mL) over 50 minutes under an ice-bath. After stirring for 15 minutes under the bath, the reaction was quenched by adding saturated ammonium chloride (30 mL). The mixture was partitioned between ethyl acetate (350 mL) and water (350 mL). The organic layer was washed with saturated sodium bicarbonate and brine, dried over magnesium sulfate, and evaporated to give a dark colored gum (33.9 g). The gum was dispersed in ethyl acetate-exane (1:3, 150 mL) in the presence of silica gel (150 mL). The mixture was filtered, and the filtrate was concentrated to give an yellow crystal (20.6 g). Flash silica gel column chromatography eluting with ethyl acetate-hexane = 1-20 to 4-5 afforded (5-bromo-3-pyridinyl)(5-ethyl-lH-pyrrol-2-yl)methanone as a pale yellow solid (7.11 g). (5-Bromo-3-pyridinyl)(5-ethyl-lH-pyrrol-2-yl)methanone NMR (CDC13,5): 1.33 (3H, t, J=7Hz), 2.75 (2H, q, J=7Hz), 6.14 (1H, m), 6.83 (1H, m), 8.27 (1H, m), 8.82 (1H, m), 8.98 (1H, m) MS(ESl+):m/z279(M+H) Preparation 165 To a solution of tert-butyl 4-(acetyloxy)-3-oxobutanoate (30.0 g) and ethyl 5-iodopentanoate (35.5 g) in N,N-dimethylformamide (150 mL) was added potassium carbonate (19.2 g) at room temperature. After stirring for 4 hours, the mixture was quenched by adding IN hydrochloric acid (140 mL) under an ice-bath. The mixture was partitioned between ethyl acetate (450 mL) and water (300 mL). The organic extract was washed with water (500 mL, three times) and brine, dried over magnesium sulfate, and evaporated to give a brown oil containing 1-tert-butyl 7-ethyl 2-[(acetyloxy)acetyl1Heptanedioate (63.4 g, 43% wt purity). 1-tert-Butyl 7-ethyl 2-[(acetyloxy)acetyl1Heptanedioate NMR (CDC13,8): 1.20-1.37 (5H,m), 1.46 (9H, s), 1.63 (2H,m), 1.85 (2H,m), 2.17 (3H, s), 2.30 (2H, t, J=7Hz), 3.39 (1H, t, J=7Hz), 4.11 82H, q, J=7Hz), 4.73 (1H, d, J=17Hz), 4.82 (1H, d, J=17Hz) Preparation 166 To a solution of ethyl thiophene (2.00 g) and ethyl 7-chloro-7-oxoheptanoate (5.39 g) in dichloromethane (20 mL) was added 1 M tin chloride in dichloromethane (38.9 mL) over 0.5 hour under an ice-bath (5 to 8°C). After stirring for 0.5 hour, the mixture was stirred for 0.5 hour at room temperature. The mixture was poured into ice-water (100 mL), and extracted with ethyl acetate (100 mL). The organic extract was washed with water (100 mL) and brine, dried over magnesium sulfate, and evaporated to give a brown oil. Flash silica gel column chromatography eluting with ethyl acetate-hexane = 1-10 to 3-10 afforded ethyl 7-oxo-7-(2-thienyl)heptanoate as a brown oil (5.79 g>- Ethyl 7-oxo-7-(2-thienyl)heptanoate NMR (CDC13,8): 1.25 (3H, t, J=7Hz), 1.42 (2H, m), 1.63-1.72 (4H, m), 2.31 (2H, t, J=7Hz), 2.91 (2H, t, J=7Hz), 4.12 (2H, q, J=7Hz), 7.13 (1H, m), 7.612 (1H, m), 7.70 (lH,m) The following compounds were obtained in substantially the same manner as those of Preparations 129 and 130. Preparation 167 tert-Butyl 3-(3,5-dimethyl-4-isoxazolyl)-3-oxopropanoate NMR (CDCI3,5): 1.47 (9H, s), 2.46 (3H, s), 2.68 (3H, s), 3.68 (2H, s) Preparation 168 Ethyl 4-methyl-3-oxopentanoate NMR (CDCI3,5): 1.14 (6H, d, J=7Hz), 1.28 (3H, t, J=7Hz), 2.71 (1H, quintet, J=7Hz), 3.50 (s, 2H), 4.19 (2H, q, J=7Hz), 7.06-7.18,7.56, and 7.85 (4H, m) Preparation 169 tert-Butyl 4-(methylthio)-3-oxobutanoate NMR (CDCI3, 5): 1.47 (9H, s), 2.07 (3H, s), 3.31 (2H, s), 3.58 (2H, s) Preparation 170 tert-Butyl 3-(l ,3-oxazol-5-yl)-3-oxopropanoate NMR (CDCI3, 6): (a mixture of keto- and enol-form); keto-form: 1.45 (9H, s), 3.77 (2H, s), 7.85 (1H, s), 8.04 (1H, s); enol-form: d 1.45 (9H, s), 5.54 (1H, s), 7.53 (1H,S),7.91(1H,S) The following compounds were obtained in substantially the same manner as that of Preparation 143. Preparation 171 (2-Chloro-4-pyridinyl)(5-ethyl-lH-pyrrol-2-yl)methanone NMR (CDCI3, 5): 1.32 (3H, t, J=7Hz), 2.74 (2H, q, J=7Hz), 6.13 (1H, m), 6.79 (1H, m), 7.56 (1H, d, J=5Hz), 7.69 (1H, s), 8.54 (1H, d, J=5Hz), 9.40 (lH,br) Preparation 172 (5 -Ethyl-1 H-py rrol-2-yl)(3-methoxypheny l)methanone NMR (CDCI3, 5): 1.32 (3H, t, J=7Hz), 2.74 (2H, q, J=7Hz), 3.87 (3H, s), 6.08 (1H, m), 6.83 (1H, m), 7.08 (1H, dd, J=2 Hz, 8Hz), 7.33-7.42 (2H, m), 7.47 (1H, d, J=8Hz),9.58(lH,br) MS (ESI+): m/z 230 Preparation 173 (5-Ethyl-lH-pyrrol-2-yl)(4-pyridinyl)methanone NMR (CDCI3, 5): 1.32 (3H, t, J=7Hz), 2.72 (2H, q, J=7Hz), 6.13 (1H, m), 6.81 (1H, m), 7.65 (2H, d, J=7Hz), 8.77 (2H, d, J=7Hz), 9.39 (1H, br) Preparation 174 (5 -Ethyl -1 H-py rrol -2-yl)(2-py razinyl)methanone NMR (CDCI3, 5): 1.33 (3H, t, J=7Hz), 2.77 (2H, q, J=7Hz), 6.14 (1H, m), 7.51 (1H, m), 8.65 (1H, m), 8.74 (1H, m), 9.36 (1H, br) Preparation 175 (5-Ethyl-lH-pyrrol-2-yl)(3-pyridinyl)methanone NMR (CDCI3,5): 133 (3H, t, J=7Hz), 2.76 (2H, q, J=7Hz), 6.12 (1H, m), 6.81 (1H, m), 7.42 (1H, m), 8.13 (1H, m), 8.76 (1H, m), 9.08 (1H, m), 9.36 (1H, br) Preparation 176 A mixture of 3-[(l-amino-5-ethyl-lH-pyrrol-2-yl)carbonyI]benzonitriIe (300 mg), methanesulfonylacetic acid (208 mg), l-(3-dimethylaminopropy])-3-ethylcarbodiimide hydrochloride (361 mg), and 1-hydroxybenzotriazole (254 mg) in N,N-dimethylformamide (1 mL) was stirred for 15 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with water two times, saturated sodium bicarbonate, and brine, dried over magnesium sulfate, and evaporated to give a pale brown solid. Flash silica gel column chromatography eluting with ethyl acetate-hexane = 1/2 to 1/0 afforded N-[2-(3-cyanobenzoyl)-5-ethyl-lH-pyrrol-l-yl]-2-(methylsulfonyl)acetamide as a pale brown foam, which was solidified upon standing (505 mg). N-[2-(3-Cyanobenzoyl)-5-ethyl-lH-pyrrol-l-yl]-2-(methylsulfonyl)acetamide NMR (CDC13,8): 1.29 (3H, t, J=7Hz), 2.62 (2H, q, J=7 Hz,), 3.28 (3H, s), 4.15 (2H, s), 6.12 (1H, d, J=5Hz), 6.75 (1H, d, J=5Hz), 7.58 (1H, t, J=9Hz), 7.82 (1H, d, J=9Hz), 8.01 (1H, d, J=9Hz), 8.06 (1H, s) The following compound was obtained in substantially the same manner as that of Preparation 176. Preparation 177 Ethyl 3-{[2-(4-cyanobenzoyl)-5-ethyl-lH-pyrrol-l-yl]ammo}-3-oxopropanoate NMR (CDCI3, 5): 1.20-1.37 (6H, m), 2.56 (2H, q, J=7Hz), 3.57 (2H, s), 4.30 (2H, q, J=7Hz), 6.06 (1H, d, J=5Hz), 6.68 (1H, d, J=5Hz), 7.54 (2H, d, J=9Hz), 7.84 (2H, d,J=9Hz) Example 1 To a solution of 4-[(l-amino-5-ethyl-lH-pyrrol-2-yI)carbonyl]benzonitri]e (100 mg) in toluene (1 rnL) were added l-(4-methoxyphenyl)acetone (103 mg) and p-toluene-sulfonic acid monohydrate (16 mg) at ambient temperature. The reaction mixture was heated at 80°C for 3 hours. The mixture was evaporated in vacuo. The residue was purified by flash silica gel column chromatography eluting with hexane-ethyl acetate = 20-1 and 15-1 to give 4-[7-ethyl-3-(4-methoxyphenyl)-2-methylpyrrolo[l,2-b]pyridazin-4-yl]benzonitrile (31 mg, 20.2%) as an yellow solid. 4-[7-Ethyl-3-(4-methoxyphenyl)-2-methylpyrrolo[l,2-b]pyridazin-4»yl]benzonitrile NMR (CDC13,5): 1.40 (3H, t, J=8Hz), 2.31 (3H, s), 3.16 (2H, q, J=8Hz), 3.77 (3H, s), 6.10 (1H, d, J=5Hz), 6.60 (1H, d, J=5Hz), 6.75 (2H, d, J=8Hz), 6.93 (2H, d5 J=8Hz), 7.33 (2H, d, J=8Hz), 7.53 (2H, d, J=8Hz) MS (ESI+): m/z 368 (M+H) The following compounds were obtained in substantially the same manner as that of Example 1. Example 2 Ethyl 4-(4-cyanophenyl)-2-(2-ethoxy-2-oxoethyl)-7-ethylpyrrolo[ 1,2-b]pyridazine-3-carboxylate NMR (CDCI3,5): 0.84 (3H, t, J=7Hz), 1.28 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 3.04 (2H, q, J=7Hz), 3.93 (2H, q, J=7Hz), 4.13 (3H, s), 4.19 (2H, q, J=7Hz), 6.24 (1H, d, J=5Hz)> 6.62 (1H, d, J=5Hz), 7.13 (2H, d, J=9Hz), 7.76 (2H, d, J=9Hz) . Example 3 Ethyl 4-(4-cyanophenyl)-7-ethyl-2-(trifluoromethyl)pyrrolo[ 1 ,2-b]pyridazine-3-carboxylate NMR(CDC13,5): 1.08 (3H, t,J=7Hz), 1.41 (3HSt, J=7Hz),3.11 (2H,q,J=7Hz),4.11 (2H, q, J=7Hz), 6.43 (1H, d, J=5Hz), 6.93 (1H, d, J=5Hz), 7.62 (2H, d, J=9Hz), 7.80(2H,d,J=9Hz) Example 4 4-[7-Ethyl-2-methyl-3-(3-pyridinylcarbonyl)pyrrolo[l)2-b]pyridazin-4-yl]benzonitrile NMR (CDCI3,5): 1.43 (t, J=7 Hz, 3H), 2.47 (s, 3H), 3.09 (q, J=7 Hz, 2 H), 6.35 (d, J=5 Hz, 1H), 6.74 (d, J=5 Hz, 1H), 7.23 (1H, m), 7.48 (2H, d, J=9Hz), 7.55 (2H, d, J=9Hz), 7.93 (1H, m), 8.62 (1H, m), 8.74 (1H, m) Example 5 3-[7-Ethyl-2-methyl-3-(4-pyridinyl)pyrrolo[l,2-b]pyridazin-4-yl]benzonitrile NMR (CDCJ3,8): 1.42 (3H, t, J=7Hz), 2.32 (3H, s), 3.08 (2H, q, J=7Hz), 6.15 (1H, d, J=5Hz), 6.67 (1H, d, J=5Hz), 7.00 (2H, d, J=9Hz), 7.37 (2H, m), 7.57 (2H, m), 8.50(2H,d,J=9Hz) Example 6 4-(3-Benzyl-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-4-yl)benzonitrile NMR (CDCI3,5): 1.40 (3H, t, J=8Hz), 2.35 (3H, s), 3.04 (2H, q, J=8Hz), 3.83 (3H, s), 5.94 (1H, d, J=5Hz), 6.57 (1H, d, J=5Hz), 6.98 (2H, d, J=8Hz), 7.14-7.30 (3H, m), 7.46 (2H, d, J=8Hz), 7.68 (2H, d, J=8Hz) MS (ESI+): m/z 352 (M+H) Example 7 4-(3-Chlorophenyl)-7-e(hyl-2-phenylpyrrolo[l,2-b]pyridazine-3-carbonitrile mp: 172-173°C NMR(CDCI3,8): 1.41 (3H, t,J=8Hz), 3.10 (2H,q,J=8Hz), 6.65 (lH,d, J=5Hz), 6.88 (1H, d, J=5Hz), 7.47-7.64 (6H, m), 7.70 (1H, br s), 7.81-7.90 (2H, m) Example 8 3-(3-Ethyl-7,7,9,9-tetramethyl-6,7,8,9-tetrahydropyrrolo[l,2-b]cinnolin-10- yl)benzonitrile NMR (CDCI3,8): 1.00-1.15 (12H, m), 1.37 (3H, 1, J=8Hz), 2.81 (3H, s), 3.00 (2H, q, J=8Hz), 3.82 (2H, t, J=5Hz), 5.46 (1H, d, J=5Hz), 6.46 (1H, d, J=5Hz),7.50-7.65 (3H,m),7.72(lH,m) Example 9 3-(3-Ethyl-9-oxo-6,7,8,9-tetrahydropyrrolo[l,2-b]cinnolin-10-yI)benzonitrile NMR (CDCI3,5): 1.40 (3H, t, J=8Hz), 2.08-2.22 (2H, m), 2.60 (2H, I, J=7Hz), 3.00- 3.15 (4H, m), 6.26 (1H, d, J=5Hz), 6.74 (1H, d, J=5Hz), 7.49-7.61 (3H, m), 7.74 (lH.m) MS(ESI+):m/z316(M+H) Example 10 3-(6-Ethyl-l-oxo-2,3-dihydro-lH-cyclopenta[e]pyrrolo[l,2-b]pyridazin-9-yl)benzonitrile mp: 150-154°C NMR (CDC13,5): 1.43 (3H, t, J=8Hz), 2.75 (2H, t, J=7Hz), 3.10 (2H, q, J=8Hz), 3.24 (2H, t, J=7Hz), 6.67 (1H, d, J=5Hz), 6.87 (1H, d, J=5Hz), 7.60 (1H, 1, J=8Hz), 7.75-7.90 (3H,m) MS (ES1+): m/z 324 (M+Na) Example 11 3-(7-Ethyl-2-neopentylpyirolo[l,2-b]pyridazin-4-yl)benzonitrile NMR (CDCI3, 6): 1.05 (9H, s), 1.39 (3H, t, J=8Hz), 2.68 (2H, s), 3.04 (2H, q, J=8Hz), 6.36 (1H, s), 6.48 (1H, d, J=5Hz), 6.67 (1H, d, J=5Hz), 7.51 (1H, t, J=8Hz), 7.75 (1H, br d, J=8Hz), 7.92-8.01 (2H, m) MS (ES1+): m/z 318 (M+H) Example 12 3-[7-Ethyl-2-(2-furyl)pyrrolo[l,2-b]pyridazin-4-yl]benzonitrile NMR (CDCI3, 5): 1.44 (3H, t, J=8Hz), 3.11 (2H, q, J=8Hz), 6.52-6.60 (2H, m), 6.74 (1H, d, J=5Hz), 6.98 (1H, s), 7.09 (1H, d, J=5Hz), 7.56-7.68 (2H, m), 7.78 (1H, dd, J=8,1Hz), 7.96-8.08 (2H, m) MS (ESI+): m/z 314 (M+H) Example 13 4-[7-Ethyl-2-methyl-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazin-4-yl]benzonitrile NMR (CDCI3,8): 1.38 (3H, t, J=8Hz), 2.89 (3H, s), 3.00-3.11 (5H, m), 6.09 (1H, d, J=5Hz), 6.73 (1H, d, J=5Hz), 7.45 (2H, d, J=8Hz), 7.76 (2H, d, J=8Hz) MS (ES1+): m/z 340 (M+H) Example 13-2 4-{7-Ethyl-2-[(melhylsu]fony])iriethyl]pyrro]o[l,2-]pyridazin-4-yl}benzonitrile NMR (CDCI3,5): 1.39 (3H, t, J=8Hz), 2.96-3.09 (5H, m), 4.44 (2H, s), 6.63 (1H, d, J=5Hz), 6.71 (1H, s), 6.8J (1H, d, J=5Hz), 7.79 (2H, d, J=8Hz), 7.85 (2H, d, J=8Hz) MS (ES1+): m/z 340 (M+H) Example 15 3-[7-Ethyl-2-methy]-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazin-4-yl]benzonitrile NMR (CDCI3, 5): 1.39 (3H, t, J=SHz), 2.89 (3H, s), 3.00-3.11 (5H, m), 6.09 (1H, d, J=5Hz), 6.73 (1H, d, J=5Hz), 7.54-7.63 (3H, m), 7.77 (1H, m) Example 16 To a solution of 4-[7-ethyl-3-(4-methoxyphenyl)-2-methylpyrrolo[l,2-b]pyridazin-4-yl]benzonitrile (22 mg) in N,N-dimethylformamide (1 mL) were added IN sodium hydroxide (0.12 mL) and 30% hydrogen peroxide (0.07 mL) at ambient temperature. After 1 hour stirring, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water three times and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by flash silica gel column chromatography (silica gel, 30 mL) eluting with hexane-ethyl acetate = 5-1 and 0-1 to give 4-[7-ethyl-3-(4-methoxyphenyl)-2-methylpyrrolo[l,2-b]pyridazin-4-yl]benzamide (18 mg, 78.0%) as an yellow solid. 4-[7-Ethyl-3-(4-methoxyphenyl)-2-methylpyrrolo[l,2-b]pyridazin-4-yl]benzamide NMR (CDCI3, 5): 1.41 (3H, t, J=8Hz), 2.31 (3H, s), 3.17 (2H, q, J=8Hz), 3.77 (3H, s), 5.61 (0.2H, br s), 6.02 (0.4H, br s), 6.13 (1H, d, J=5Hz), 6.60 (1H, d, J=5Hz), 6.75 (2H, d, J=8Hz), 6.95 (2H, d, J=8Hz), 7.31 (2H, d, J=8Hz), 7.68 (2H, d, J=8Hz) MS(ESI+):m/z386(M+H) The following compound was obtained in substantially the same manner as that of Example 16. Example 17 3-[2-(Dimethylai"nino)-7-ethyl-3-(mcthylsu]fonyl)pyrrolo[l,2-b]pyridazin-4-yl]benzamide NMR (CDCI3, 5): 1.32 (3H, t, J=7Hz), 2.90 (6H, s), 2.95 (2H, q, J=7Hz), 3.36 (3H, s), 6.21 (1H, d, J=5Hz), 6.79 (1H, d, J=5Hz), 7.44 (1H, s, br), 7.52-7.56 (2H, m), 7.90 (1H, s), 7.94-8.06 (2H, m) MS (ES1+): m/z 387 (M+H) Example 18 3-(7-Ethyl-2-neopentylpyrrolo[l,2-b]pyridazin-4-yl)benzamide NMR (CDCI3, 5): 1.05 (9H, s), 1.39 (3H, t, J=8Hz), 2.68 (2H, s), 3.04 (2H, q, J=8Hz), 5.70 (1H, br s), 6.11 (1H, br s), 6.41 (1H, s), 6.52 (1H, d, J=5Hz), 6.65 (1H, d, J=5Hz), 7.59 (1H, t, J=8Hz), 7.85-7.93 (2H, m), 8.15 (1H, br s) MS (ES1+): m/z 336 (M+H) Example 19 3-[7-Ethyl-2-(2-furyl)pyrrolo[l,2-b]pyridazin-4-yl]benzamide NMR (CDCI3, 8): 1.43 (3H, t, J=8Hz), 3.10 (2H, q, J=8Hz), 5.70 (1H, br s), 6.13 (1H, br s), 6.53-6.60 (2H, m), 6.71 (1H, d, J=5Hz), 7.02 (1H, s), 7.06 (1H, d, J=5Hz), 7.55-7.65 (2H, m), 7.79-7.98 (2H, m), 8.02 (1H, br s) MS(ESI+):m/z332(M+H) Example 20 5-[2-({[4-(Aminocarbonyl)benzyl]oxy}methyl)-4-(5-bromo-3-pyridinyl)-7- ethylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (DMSO-d6,5): 1.27-1.45 (7H, m), 1.99 (2H, m), 2.96 (2H, m), 3.40 (2H, m), 4.67 (2H, s), 4.72 (2H, s), 5.88 (1H, d, J=5Hz), 6.67 (1H, d, J=5Hz), 7.35 (1H, s, br), 7.44 (2H, d, J=8Hz), 7.86 (2H, d, J=8Hz), 7.96 (1H, s, br), 8.21 (1H, m), 8.60 (lH,m),8.86(lH,m) Example 21 To a solution of ethyl 6-(3-cyanobenzoyl)-7-oxooctanoate (3.18 g) in toluene (30 mL) was added 2-ethyl-lH-pyrrol-l-amine (1.17 g) and p-toluenesulfonic acid monohydrate (96 mg) at ambient temperature. The reaction mixture was refluxed for 1 hour. The mixture was evaporated in vacuo. The residue was purified by flash silica gel chromatography (silica gel, 200 mL) eluting with hexane-ethyl acetate = 20-1, 15-1, and 10-1 to give ethyl 5-[4-(3-cyanophenyl)-7-ethy]-2-methy]pyrrolo[l,2-b]pyridazin-3-yl]pentanoate (3.29 g, 83.8%) as an yellow oil. Ethyl 5-[4-(3-cyanophenyl)-7-ethyl-2-methylpyrrolo[l)2-b]pyridazin-3-yl]pentanoate NMR (CDC13,5); 1.23 (3H, l, J=8Hz), 1.32-1.58 (7H, m), 2.18 (2H, t, J=8Hz), 2.35- 2.45 (2H,m), 3.01 (2H,q, J=8Hz),4.1()(2H,q, J=8Hz),5J9 (lH,d, J=5Hz), 6.51 (1H, d, J=5Hz), 7.57-7.67 (3H, m), 7.75 (1H, m) The following compounds were obtained in substantially the same manner as that of Example 21. Example 22 Ethyl 2,4-diisopropylpyrrolo[l,2-b]pyridazine-3-carboxylale NMR (300 MHz, CDCI3, 8): 1.32 (6H, d, J=7.5Hz), 1.39 (3H, t, J=7.5Hz), 1.46 (6H, d, J=7.5Hz), 2.91-3.05 (1H, m), 3.05-3.20 (1H, m), 4.38 (2H, q, J=7.5Hz), 6.64-6.68 (1H, m), 6.76-6.80 (1H, m), 7.65-7.68 (1H, m) MS(ES+)m/e275.33 Example 23 ■ Ethyl 4-(2-chlorophenyl)-2-isopropylpyiTOlo[ 1,2-b]pyridazine-3-carboxylate NMR (300 MHz, CDCI3, §): 0.89 (3H, t, J=7.5Hz), 1.30-1.40 (6H, m), 3.36-3.51 (1H, m), 4.00 (2H, q, J=7.5Hz), 6.10-6.18 (1H, m), 6.75-6.84 (1H, m), 7.28-7.45 (3H, m), 7.45-7.55 (1H, m), 7.75-7.81 (1H, m) Example 24 Ethyl 2-isopropyl-4-(2-naphthyl)pyrrolo[l ,2-b]pyridazine-3-carboxylate NMR (300 MHz, CDCI3, 5): 0.78 (3H, t, J=7.5Hz), 1.38 (6H, d, J=7.5Hz), 3.24-3.35 (lH,m), 3.95 (2H,q,J=7.5Hz), 6.36-6.40 (lH,m), 6.80-6.85 (lH,m), 7.50-7.54 (3H, m), 7.78-7.82 (1H, m), 7.82-8.00 (4H, m) MS (ES+) m/e 359.56 Example 25 Ethyl 5-{7-ethyl-2-methyl-4-[3-(trifluoromethyl)phenyl]pyrrolo[l,2-b]pyridazin-3-yl}pentanoate NMR (CDCI3,5): 1.22 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.40-1.59 (4H, m), 2.14 (2H, t, J=7Hz), 2.38-2.46 (2H, m), 2.55 (3H, s), 3.01 (2H, q, J=7Hz), 4.10 (2H, q, J=7Hz), 5.83 (1H, d, J=4Hz), 6.51 (1H, d, J=4Hz), 7.53-7.64 (3H, m), 7.71 (1H, d, J=8Hz) MS (ES1+): m/z 433 (M+H) Example 26 Ethyl 5-[7-ethyl-2-methyl-4-(5-methyl-3-pyridinyl)pynolo[l,2-b]pyridazin-3- yl]pentanoate NMR (CDCI3, 5): 1.23 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.38-1.60 (4H, m), 2.18 (2H, t, J=7Hz), 2.42 (3H, s), 2.38-2.50 (2H, m), 2.55 (3H, s), 3.00 (2H, q, J=7Hz), 4.09 (2H, q, J=7Hz), 5.87 (1H, d, J=4Hz), 6.51 (1H, d, J=4Hz), 7.50 (1H, s), 8.39 (lH,s),8.53(lH,s) MS (ES1+): m/z 380 (M+H) Example 27 Ethyl 5-[7-ethyl-4-(3-methoxy-5-isoxazolyl)-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin- 3-yl]pentanoate NMR (CDCI3, 5): 1.25 (3H, t, J=7Hz), 1.36 (3H, t, J=7Hz), 1.55-1.64 (2H, m), 1.64- 1.80 (2H, m), 2.33 (2H, t, J=7Hz), 2.74-2.85 (2H, m), 3.03 (2H, q, J=7Hz), 3.43 (3H, s), 4.08 (3H, s), 4.12 (2H, q, J=7Hz), 4.62 (2H, s), 6.28 (1H, s), 6.38 (1H, d, J=4Hz),6.65(lH,d,J=4Hz) MS (ES1+): m/z 416 (M+H) Example 28 Ethyl 5-{7-ethyl-2-methyl-4-[3-(l,3-oxazol-5-yl)phenyl]pyrrolo[l,2-b]pyridazin-3- yljpentanoate NMR (CDCI3, 5): 1.20 (3H, t, J=7Hz), 1.35 (3H, t, J=7Hz), 1.40-1.63 (4H, m), 2.17 (2H, 1, J=7Hz), 2.44-2.57 (2H, m), 2.56 (3H, s), 3.02 (2H, q, J=7Hz), 4.05 (2H, q, J=7Hz), 5.89 (1H, d, J=4Hz), 6.50 (1H, d, J=4Hz), 7.33 (1H, d, J=8Hz), 7.39 (1H, s), 7.53 (1H, t, J=8Hz), 7.66 (1H, m), 7.74 (1H, d, J=8Hz), 7.93 (1H, s) Example 29 Ethyl 5-[4-(3,4-dichlorophenyl)-7-ethyl-2-melhylpyrrolo[l,2-b]pyridazin-3-yl]penlanoate NMR (CDC13,5): 1.24 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.38-1.48 (2H, m), 1.50- 1.65 (2H, m), 2.20 (2H, t, J=7Hz), 2.38-2.47 (2H, m), 2.54 (3H, s), 3.00 (2H, q, J=7Hz), 4.12 (2H, q, J=7Hz), 5.87 (1H, d, J=4Hz), 6.51 (1H, d, J=4Hz), 7.19 (1H, dd, J=2 Hz, 8Hz), 7.46 (1H, d, J=2Hz), 7.56 (1H, d, J=8Hz) MS (ESI+): m/z 433 (M+H) Example 30 Ethyl 5-[4-(4-chloro-2-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3- yl]pentanoate NMR (CDCI3, 5): 1.24 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.44-1.67 (4H, m), 2.15- 2.26 (2H, m), 2.42-2.56 (2H, m), 2.56 (3H, s), 3.01 (2H, q, J=7Hz), 4.10 (2H, q, J=7Hz), 5.95 (1H, d, J=3Hz), 6.54 (1H, d, J=3Hz), 7.40 (1H, dd, J=2 Hz, 4Hz), 7.54 (1H, d, J=2Hz), 8.67 (1H, d, J=4Hz) MS (ES1+): m/z 400 (M+H) Example 31 Ethyl 5-[4-(5-chloro-2-thienyl)-7-ethyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3- yl]pentanoate NMR (CDCI3, 5): 1.25 (3H, t, J=7Hz), 1.36 (3H, t, J=7Hz), 1.48-1.74 (4H, m), 2.28 (2H, t, J=7Hz), 2.68-2.77 (2H, m), 3.02 (2H, q, J=7Hz), 3.44 (3H, s), 4.12 (2H, q, J=7Hz), 4.60 (2H, s), 6.25 (1H, d, J=4Hz), 6.60 (1H, d, J=4Hz), 6.97 (2H, m) MS (ES1+): m/z 435 (M+H) Example 32 Ethyl 5-[7-ethyl-4-(6-methoxy-2-pyrazinyl)-2-methylpyrrolo[l52-b]pyridazin-3- yl]pentanoate NMR (CDCI3, 5): 1.23 (3H, t, J=7Hz), J .37 (3H, t, J=7Hz), 1.52-1.68 (4H, m), 2.23 (2H, t, J=7Hz), 2.48-2.55 (2H, m), 2.56 (3H, s), 3.(32 (2H, q, J=7Hz), 3.98 (3H, s), 4.09 (2H, q, J=7Hz), 6.03 (1H, d, J=4Hz), 6.55 (1H, d, J=4Hz), 8.30 (1H, s), 8.33 (lH,s) MS (ESI+): m/z 397 (M+H) Example 33 Ethyl 5-[4-(l-benzofuran-2-yl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDCI3,5): 1.23 (3H, t, J=7Hz), 1.38 (3H, t, J=7Hz), 1.62-1.83 (4H, m), 2.33 (2H, t, J=7Hz), 2.57 (3H, s), 2.69-2.78 (2H, m), 3.03 (2H, q, J=7Hz), 4.12 (2H, q, J=7Hz), 6.48 (1H, d, J=4Hz), 6.59 (1H, d, J=4Hz), 7.15 (1H, s), 7.26-7.42 (2H, m), 7.57 (1H, d, J=8Hz), 7.68 (1H, d, J=8Hz) MS (ESI+): m/z 405 (M+H) Example 34 Ethyl 5-[4-(l-benzothien-2-yl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDCI3, 5): 1.21 (3H, t, J=7Hz), 1.35 (3H, t, J=7Hz), 1.52-1.69 (4H, m), 2.23 (2H, t, J=7Hz), 2.56 (3H, s), 2.61-2.70 (2H, m), 3.02 (2H, q, J=7Hz), 4.07(2H, q, J=7Hz), 6.21 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 7.35-7.43 (3H, m), 7.81-7.92 (2H,m) Example 35 Ethyl 5-[7-ethyl-2-methyl-4-(l,3-oxazol-5-yl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDCI3, 5): 1.25 (3H, t, J=7Hz), 1.36 (3H, t, J=7Hz), 1.53-1.66 (2H, m), 1.66- 1.83 (2H, m), 2.34 (2H, t, J=7Hz), 2.56 (3H, s), 2.62-2.73 (2H, m), 3.02 (2H, q, J=7Hz), 4.13 (2H, q, J=7Hz), 6.42 (1H, d, J=4Hz), 6.58 (1H, d, J=4Hz), 7.50 (1H, s),8.10(lH,s) MS(ESl+):m/z356(M+H) Example 36 Ethyl 5-(7-ethyl-2-methyl-4-phenylpyrrolo[l,2-b]pyridazin-3-yl)penlanoate NMR (CDCI3, 5): 1.23 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.40-1.60 (4H, m), 2.15 (2H, t, J=7Hz), 2.41-2.48 (2H, m), 2.55 (3H, s), 3.02 (2H, q, J=7Hz), 4.08 (2H, q, J=7Hz), 5.88 (1H, d, J=4Hz), 6.48 (1H, d, J=4Hz), 7.31-7.34 (2H, m), 7.40-7.49 (3H,m) MS(ESl+):m/z365(M+H) Example 37 Elhyl 5-[7-ethyl-2-methyl-4-(6-quinolinyl)pyrrolo[l,2-b]pyridazin-3-yl]penlanoale NMR (CDCI3,8): 1.18 (3H, t, J=7Hz), 1.39 (3H, t, J=7Hz), 1.39-1.55 (4H, m), 2.14 (2H, d, J=7Hz), 2.44-2.55 (2H, m), 2.58 (3H, s), 3.03 (2H, q, J=7Hz), 4.03 (2H, q, J=7Hz), 5.86 (1H, d, J=4Hz), 6.51 (1H, d, J=4Hz), 7.45-7.52 (1H, m), 7.69 (1H, dd, J=2Hz, 8Hz), 7.84 (1H, d, J=2Hz), 8.20 (2H, d, J=8Hz), 9.00 (1H, m) Example 38 Ethyl 7-{4-[4-({[(benzyloxy)carbonyl]amino}sulfonyl)phenyl]-7-ethyl-2- methylpyrrolo[l,2-b]pyridazin-3-yl}heptanoate NMR (CDC13,5): 1.12-1.23 (7H,m), 1.33-1.51 (7H,s), 2.17 (2H,t, J=7Hz), 2.35 (2H, m), 2.56 (3H, s), 3.02 (2H, q, J=7Hz), 4.11 (2H, q, J=7Hz), 5.17 (2H, s), 5.78 (1H, d, J=5Hz), 6.52 (1H, d, J=5Hz), 7.29-7.38 (5H, m), 7.49 (2H, d, J=9Hz), 7.87 (1H, s.br), 8.11 (2H, d, J=9Hz) MS (ESI+): m/z 606 (M+H) MS (ESI"): m/z 604 (M-H) Example 39 2-{[4-(3-Chlorophenyl)-7-ethy]-2-methylpyrrolo[l,2-b]pyridazJn-3-y]]methyl}-l,3- propanediol NMR (CDCI3,8): 1.26 (3H, t, J=7Hz), 1.38 (3H, t, J=7Hz), 1.64-1.82 (3H, m), 2.59 (3H, s), 3.02 (2H, q, J=7Hz), 3.45 (2H, m), 3.63 (2H, m), 4.12 (2H, q, J=7Hz), 5.93 (1H, d), J=5Hz), 6.53 (1H, d, J=5Hz), 7.28 (1H, m), 7.42-7.44 (3H, m) Example 40 Ethyl 5-{7-ethyl-2-methyl-4-[3-(methylsulfonyl)phenyl]pyrrolo[l,2-b]pyridazin-3- yljpentanoate NMR (CDCI3,5): 1.22 (3H, t, J=8Hz), 1.33-1.57 (7H, m), 2.18 (2H, t, J=8Hz), 2.35- 2.45 (2H, m), 2.56 (3H, s), 3.01 (2H, q, J=8Hz), 3.12 (3H, s), 4.08 (2H, q, J=8Hz), 5.80 (1H, d, J=5Hz), 6.51 (1H, d, J=5Hz), 7.64-7.74 (2H, m), 7.96 (1H, br s), 8.04 (lH,m) MS (ESI+): rn/z 443 (M+H) Example 41 Ethyl 5-[4-(2-chloro-4-pyridinyl)-7-ethy]-2-methylpyrrolo[l,2-b]pyridazin-3- yljpentanoate NMR (CDCI3, 8): 1.23 (3H, t, J=8Hz), 1.30-1.62 (7H, m), 2.21 (2H, t, J=8Hz), 2.35- 2.45 (2H, m), 2.55 (3H, s), 3.00 (2H, q, J=8Hz), 4.10 (2H, q, J=8Hz), 5.85 (1H, d, J=5Hz), 6.53 (1H, d, J=5Hz), 7.24 (1H, dd, J=7,1Hz), 7.35 (1H, br s), 8.53 (1H, d, J=7Hz) MS (ES1+): m/z 400 (M+H) Example 42 Ethyl 5-[7-ethyl-2-methyl-4-(3-nitrophenyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDCI3,5): 1.21 (3H, t, J=8Hz), 1.34-1.59 (7H, m), 2.17 (2H, t, J=8Hz), 2.37- 2.47 (2H, m), 2.57 (3H, s), 3.01 (2H, q, J=8Hz), 4.08 (2H, q, J=8Hz), 5.81 (1H, d, J=5Hz), 6.52 (1H, d, J=5Hz), 7.64-7.74 (2H, m), 8.25 (1H, br s), 8.33 (1H, m) MS (ES1+): m/z 410 (M+H) Example 43 Ethyl 4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazine-3-carboxylate NMR (CDCI3,8): 0.98 (3H, t, J=8Hz), 2.55 (3H, s), 4.05 (2H, q, J=8Hz), 6.35 (1H, m), 6.81 (1H, m), 7.12-7.22 (2H, m), 7.41-7.50 (2H, m), 7.76 (1H, m) MS (ES1+): m/z 359 (M+H) Example 44 4-(3-Butyl-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-4-yl)benzonitrile NMR (CDCI3,8): 0.78 (3H, t, J=8Hz), 1.12-1.43 (7H,m), 2.31-2.40 (2H, m), 2.56 (3H, s), 3.00 (2H, q, J=8Hz), 5.79 (1H, d, J=5Hz), 6.50 (1H, d, J=5Hz), 7.47 (2H, d,J=8Hz),7.77(2H,d,J=8Hz) MS(ESl+):m/z318(M+H) Example 45 Ethyl 5-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yljpentanoate NMR (CDCI3,8): 1.24 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.40-1.65 (4H, m), 2.21 (2H, t, J=7Hz), 2.37-2.49 (2H, m), 2.56 (3H, s), 3.00 (2H, q, J=7Hz), 4.10 (2H, q, J=7Hz), 5.87 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 7.85 (1H, m), 8.53 (1H, d, J=2Hz),8.77(lH,d,J=2Hz) MS:(m/z)444,446(M+H) Example 46 Ethyl 5-{4-(2-chloro-4-pyridinyl)-7-ethyl-2-[(methylthio)methyl]pyrrolo[ 1,2-b]pyridazin- 3-yl}pentanoate NMR (CDCI3,5): 1.24 (3H, t, J=7Hz), 1.36 (3H, t, J=7Hz), 1.40-1.63 (4H, m), 2.18 (3H, s), 2.20 (2H, t, J=7Hz), 2.48-2.58 (2H, m), 3.02 (2H, q, J=7Hz), 3.81 (2H, s), 4.10 (2H, q, J=7Hz), 5.89 (1H, d, J=4Hz), 6.57 (1H, d, J=4Hz), 7.27 (1H, m), 7.38 (1H, s), 8.53 (1H, d, J=4Hz) MS:(m/z)446(M+H) Example 47 Ethyl 6-[4-(3-cyanophenyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl1Hexanoate NMR (CDCI3,8): 1.15-1.29 (5H, m), 1.32-1.61 (7H, m), 2.20 (2H, t, J=8Hz), 2.33- 2.43 (2H, m), 2-6 (3H, s), 3.01 (2H, q, J=8Hz), 4.10 (2H, q, J=8Hz), 5.79 (1H, d, J=5Hz), 6.51 (1H, d, J=5Hz), 7.57-7.67 (3H, m), 7.75 (1H, m) MS (ESI): m/z 404 (M+H) Example 48 Ethyl 5-[4-(6-chloro-2-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3- yl]pentanoate NMR (CDCI3,8): 1.23 (3H, t, J=7Hz), 1.36 (3H, t, J=7Hz), 1.46-1.65 (4H, m), 2.22 (2H, t, J=7Hz), 2.46-2.57 (2H, m), 2.54 (3H, s), 3.00 (2H, q, J=7Hz), 4.09 (2H, q, J=7Hz), 5.95 (lH,d,J=4Hz), 6.51 (lH,d,J=4Hz), 7.38-7.47 (2H,m), 7.80 (lH,t, J=8Hz) MS (ES1+): m/z 400 sample 49 hyl 5-[7-ethyl-4-(3-methoxyphenyl)-2-methylpyrrolo[ 1,2-b]pyridazin-3-yl]pentanoate NMR (CDC13,5): 1.23 (3H, I, J=7Hz), 1.36 (3H, t, J=7Hz), 1.40-1.62 (4H, m), 2.17 (2H, t, J=7Hz), 2.43-2.52 (2H, m), 2.54 (3H, s), 3.00 (2H, q, J=7Hz), 3.83 (3H, s), 4.08 (2H, q, J=7Hz), 5.91 (1H, d, J=4Hz), 6.49 (1H, d, J=4Hz), 6.87-6.99 (3H, m), 7.37(lH,t,J=8Hz) MS (ESI+): m/z 395 Example 50 Lthyl 5-[4-(3,5-dichlorophenyl)-7-ethyl-2-methy]pyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDCI3, 8): 1.23 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.39-1.52 (2H, m), 1.52- 1.64 (2H, m), 2.22 (2H, t, J=7Hz), 2.38-2.48 (2H, m), 2.54 (3H, s), 3.00 (2H, q, J=7Hz), 4.10 (2H,q,J=7Hz), 5.88 (lH,d, J=4Hz), 6.51 (1H, d,J=4Hz), 7.25 (2H, m),7.45(lH,m) MS (ES1+): m/z 433 Example 51 Ethyl 5-[4-(5-chloro-2-thienyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDC13,5): 1.25 (3H, t, J=7Hz), 1.36 (3H,t, J=7Hz), 1.46-1.58 (2H,m), 1.60- 1.74 (2H, m), 2.28 (2H, t, J=7Hz), 2.53 (3H, s), 2.56-2.66 (2H, m), 2:98 (2H, q, J=7Hz), 4.12 (2H, q, J=7Hz), 6.20 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 6.94 (1H, d,J=4Hz),6.98(lH,d,J=4Hz) MS(ESI+):m/z405 Example 52 Ethyl 5-[7-ethyl-4-(3-fluorophenyl)-2-methylpynolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDCI3, 5): 1.23 (3H,t, J=7Hz), 139 (3H,t,J=7Hz), 1.38-1.50 (2H,m), 1.50- 1.63 (2H, m), 2.17 (2H, t, J=7Hz), 2.39-2.48 (2H, m), 2.54 (3H, s), 3.03 (2H, q, J=7Hz), 4.09 (2H, q, J=7Hz), 5.88 (1H, d, J=4Hz), 6.50 (1H, d, J=4Hz), 7.03-7.16 (3H,m), 7.38-7.47 (lH.m) MS (ES1+): m/z 383 Example 53 Ethyl 5-[7-ethyl-2-methyl-4-(3-quinolinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDC13,5): 1.18 (3H, t, J=7Hz), 1.38 (3H, t, J=7Hz), 1.40-1.60 (4H, m), 2.16 (2H, t, J=7Hz), 2.44-2.56 (2H, m), 2.59 (3H, s), 3.04 (2H, q, J=7Hz), 4.03 (2H, q, J=7Hz), 5.89 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 7.62 (1H, t, J=8Hz), 7.80 (1H, t, J=8Hz), 7.90 (1H, d, J=8Hz), 8.21 (2H, m), 8.90 (1H, d, J=2Hz) MS (ESI+): m/z 416 Example 54 Ethyl 5-[7-ethyl-2-methyl-4-(4-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDCI3,6): 1.23 (3H, t, J=7Hz), 1.38 (3H, t, J=7Hz), 1.40-1.64 (4H, m), 2.19 (2H, t, J=7Hz), 2.38-2.52 (2H, m), 2.55 (3H, s), 3.02 (2H, q, J=7Hz), 4.09 (2H, q, J=7Hz), 5.83 (1H, d, J=4Hz), 6.51 (1H, d, J=4Hz), 7.29 (2H, m), 8.72 (2H, m) MS (ESI+): m/z 366 Example 55 Ethyl 5-[7-ethyl-4-(3-methoxy-5-isoxazolyl)-2-methylpyrrolo[l,2-b]pyridazin-3- yl]pentanoate NMR (CDCI3, 5): 1.25 (3H, t, J=7Hz), 1.36 (3H, t, J=7Hz), 1.55-1.82 (4H, m), 2.33 (2H, t, J=7Hz), 2.55 (3H, s), 2.62-2.72 (2H, m), 2.99 (2H, q, J=7Hz), 4.08 (3H, s), 4.12 (2H, q, J=7Hz), 6.26 (1H, s), 6.34 (1H, d, J=4Hz), 6.58 (1H, d, J=4Hz) Example 56 Ethyl 5-[7-ethyl-2-methyl-4-(5-methyl-3-isoxazolyl)pyrrolo[l,2-b]pyridazin-3- yljpentanoate NMR (CDCI3, 5): 1.25 (3H, t, J=7Hz), 1.36 (3H, t, J=7Hz), 1.50-1.75 (4H, m), 2.29 (2H, t, J=7Hz), 2.55 (6H, s), 2.56-2.65 (2H, m), 2.99 (2H, q, J=7Hz), 4.11 (2H, q, J=7Hz), 6.16 (1H, d, J=4Hz), 6.22 (1H, s), 6.54 (1H, d, J=4Hz) MS (ESI+): m/z 370 Example 57 Ethyl 5-[4-(2-chloro-4-pyridinyl)-7-ethyl-2-(methoxymethyl)pyrrolol 1,2-b]pyridazin-3- yl]pentanoate NMR (CDC13,5): 1.23 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.36-1.63 (4H, m), 2.20 (2H, t, J=7Hz), 2.48-2.63 (2H, m), 3.03 (2H, q, J=7Hz), 3.45 (3H, s), 4.09 (2H, q, J=7Hz), 4.62 (2H, s), 5.89 (1H, d, J=4Hz), 6.60 (1H, d, J=4Hz), 7.26 (1H, m), 7.37 (1H, s), 8.53 (1H, d, J=5Hz) MS (ES1+): m/z 430 Example 58 Ethyl 5-[7-ethyl-2-(methoxymethyl)-4-(3-methoxyphenyl)pyrrolo[l,2-b]pyridazin-3- yl]pentanoate NMR (CDCI3,8): 1.22 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.40-1.63 (4H, m), 2.16 (2H, t, J=7Hz), 2.54-2.65 (2H, m), 3.04 (2H, q, J=7Hz), 3.45 (3H, s), 3.83 (3H, s), 4.08 (2H, q, J=7Hz), 4.62 (2H, s), 5.96 (1H, d, J=4Hz), 6.56 (1H, d, J=4Hz), 6.87-7.00 (3H, m), 7.38 (1H, t, J=8Hz) MS (ES1+): m/z 425 Example 59 Ethyl 5-[7-ethyl-2-(methoxymethyl)-4-(6-quinolinyl)pyrrolo[l,2-b]pyridazin-3- yljpentanoate NMR (CDCI3, 5): 1.17 (3H, t, J=7Hz), 1.43 (3H, t, J=7Hz), 1.36-1.58 (4H, m), 2.10 (2H, m), 2.56-2.68 (2H, m), 3.07 (2H, q, J=7Hz), 3.48 (3H, s), 4.02 (2H, q5 J=7Hz), 4.66 (2H, s), 5.90 (1H, d, J=4Hz), 6.56 (1H, d, J=4Hz), 7.45-7.50 (1H, m), 7.72 (1H, dd, J=2 Hz, 8Hz), 7.86 (1H, d, J=2Hz), 8.16-8.24 (2H, m), 8.98 (1H, m) Example 60 Ethyl 5-[7-ethyl-2-(methoxymethyl)-4-(3-pyridinyl)pyrrolo[l,2-b]pyridazin-3- y]]pentanoate NMR (CDCI3, §): J .22 (3H, t, J=7Hz), 1.38 (3H, t, J=7Hz), 1.40-1.60 (4H, m), 2.17 (2H, t, J=7Hz), 2.52-2.64 (2H, m), 3.04 (2H, q, J=7Hz), 3.46 (3H, s), 4.10 (2H, q, J=7Hz), 4.63 (2H, s), 5.89 (1H, d, J=4Hz), 6.58 (1H, d, J=4Hz), 7.42 (1H, m), 7.71 (1H, m), 8.62 (1H, m), 8.70 (1H, m) MS (ES1+): m/z 396 Example 61 Ethyl 5-[4-(3-chlorophenyl)-7-elhyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3- yljpentanoate NMR (CDCI3, 5): 1.23 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.40-1.58 (4H, m), 2.17 (2H, t, J=7Hz), 2.51-2.62 (2H, m), 3.03 (2H, q, J=7Hz), 3.45 (3H, s), 4.08 (2H, q, J=7Hz), 4.61 (2H, s), 5.92 (1H, d, J=4Hz), 6.56 (1H, d, J=4Hz), 7.25 (1H, m), 7.37 (lH,s), 7.42 (2H,m) Example 62 Ethyl 5-[7-ethyl-2-methyl-4-(3-methylphenyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR(CDCl3,5):1.23(3H,tJ=7Hz),1.37(3H,t,J=7Hz),1.40-1.60(4H,m),2.16 (2H, t, J=7Hz), 2.40 (3H, s), 2.40-2.50 (2H, m), 2.54 (3H, s), 3.03 (2H, q, J=7Hz), 4.08 (2H, q, J=7Hz), 5.90 (1H, d, J=4Hz), 6.49 (1H, d, J=4Hz), 7.10-7.15 (2H, m), 7.24 (lH,m), 7.33 (lH,m) MS:(m/z)379(M+H) Example 65 Ethyl 5-[7-ethyl-2-(methoxymethyl)-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3- yl]pentanoate NMR (CDCI3,8): 1.23 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.40-1.60 (4H, m), 2.18 (2H, t, J=7Hz), 2.42 (3H, s), 2.48-2.63 (2H, m), 3.05 (2H, q, J=7Hz), 3.46 (3H, s), 4.08 (2H, q, J=7Hz), 4.62 (2H, s), 5.90 (1H, d, J=4Hz), 6.57 (1H, d, J=4Hz), 7.51 (lH,s), 8.41 (lH.s), 8.53 (lH,s) MS(ESI+):m/z410 Example 66 Ethyl 5-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-l]pentanoate NMR (CDCI3, 5): 1.24 (3H, t, J=7Hz), 1.37 (3H, 1, J=7Hz), 1.40-1.65 (4H, m), 2.21 (2H, I, J=7Hz), 2.37-2.49 (2H, m), 2.56 (3H, s), 3.00 (2H, q, J=7Hz), 4.10 (2H, q, J=7Hz), 5.87 (lH,d,J=4Hz), 6.53 (!H,d, J=4Hz), 7.85 (lH,m), 8.53 (lH,d, J=2Hz),8.77(lH,d,J=2Hz) MS (ES1+): m/z 444, 446 example 67 Ethyl 5-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3- d]pentanoate NMR (CDCI3, 5): 1.23 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.40-1.63 (4H, m), 2.19 (2H, t, J=7Hz), 2.50-2.66 (2H, m), 3.03 (2H, q, J=7Hz), 3.46 (3H, s), 4.10 (2H, q, J=7Hz), 4.62 (2H, s), 5.91 (1H, d, J=4Hz), 6.60 (1H, d, J=4Hz), 7.88 (1H, m), 8.55 (1H, d, J=2Hz), 8.77 (1H, d, J=2Hz) MS (ES1+): m/z 474, 476 Example 68 Ethyl 5-[4-(5,6-dichloro-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3- yl]pentanoate NMR (CDCI3, 8): 1.24 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.36-1.60 (4H, m), 2.23 (2H, t, J=7Hz), 2.37-2.50 (2H, m), 2.55 (3H, s), 3.02 (2H, q, J=7Hz), 4.12 (2H, q, J=7Hz), 5.87 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 7.81 (1H, d, J=2Hz), 8.30 (1H, d,J=2Hz) MS (ESI+): m/z 434 Example 69 Ethyl 4-[7-ethyl-2-(methoxymethyl)-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3- yl]butanoate NMR (CDCI3,6): 1.37 (3H, t, J=7Hz), 1.65-1.78 (2H, m), 2.16-2.25 (2H, m), 2.42 (3H, s), 2.53-2.65 (2H, m), 3.04 (2H, q, J=7Hz), 3.46 (3H, s), 4.12 (2H, q, J=7Hz), 4.67 (2H, m), 5.91 (1H, d, J=4Hz), 6.58 (1H, d, J=4Hz), 7.53 (1H, s), 8.43 (1H, s), 8.54 (1H,s) MS (ESI+): m/z 396 Example 70 Ethyl 3-[7-ethyl-2-(me1hoxymelhyl)-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3- yl]propanoate NMR (CDC13, 5): 1.25 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 2.35-2.55 (2H, m), 2.42 (3H, s), 2.84-2.96 (2H, m), 3.04 (2H, q, J=7Hz), 3.46 (3H, s), 4.08 (2H, q, J=7Hz), 4.65 (2H, s), 5.91 (1H, d, J=4Hz), 6.61 (1H, d, J=4Hz), 7.51 (1H, s), 8.41 (1H, s), 8.52 (lH,s) Example 71 Ethyl 4-[7-ethyl-2-methyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3- yl]butanoate NMR (CDCI3, 5): 1.20 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.66-1.82 (2H, m), 2.16- 2.28 (2H, m), 2.42 (3H, s), 2.44-2.53 (2H, m), 2.59 (3H, s), 3.02 (2H, q, J=7Hz), 4.12 (2H, q, J=7Hz), 5.87 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 7.51 (1H, s), 8.41 (1H, d, J=2Hz), 8.53 (1H, d, J=2Hz) MS (ESI+): m/z 366 Example 72 Ethyl 3-[7-ethyl-2-methyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3- yl]propanoate NMR (CDCI3, 8): 1.24 (3H,t, J=7Hz), 1.37 (3H, t, J=7Hz), 2.30-2.43 (2H, m), 2.42 (3H, s), 2.58 (3H, s), 2.76-2.86 (2H, m), 3.02 (2H, q, J=7Hz), 4.10 (2H, q, J=7Hz), 5.87 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 7.48 (1H, s), 8.40 (1H, d, J=2Hz), 8.53 (lH,d,J=2Hz) MS(ESl+):m/z352 Example 73 Ethyl 3-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3- yl]propanoale NMR (CDC13, 5): J .21 (3H, t, J=7Hz), 139 (2H, t, J=7Hz), 235 (2H, t, J=7Hz), 2.58 (3H, s), 2.74-2.83 (2H, m), 3.01 (2H, q, J=7Hz), 4.08 (2H, q, J=7Hz), 5.89 (1H, d, J=4Hz), 6.55 (1H, d, J=4Hz), 7.87 (1H, s), 8.53 (1H, s), 8.79 (1H, s) MS: (m/z) 416 (M+),418 (M+-2), 85(bp) Example 74 Ethyl 5-[4-(3-cyanophenyl)-7-ethyl-2-(melhoxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDC13, 5): 1.23 (3H, t, J=8Hz), 132-1.55 (5H, m), 2.16 (2H, t, J=8Hz), 2.46- 2.57 (2H, m), 3.03 (2H, q, J=8Hz), 3.46 (3H, s), 4.09 (1H, q, J=8Hz), 4.62 (2H, s), 534 (1H, d, J=5Hz), 6.57 (1H, d, J=5Hz), 7.59-7.64 (2H, m), 7.68 (1H, br s), 7.75 (lH,m) MS (ESI+): 420 (M+H) Example 75 Ethyl 5-[2-[(acetyloxy)methyl]-4-(5-bromo-3-pyridinyl)-7-ethylpyrrolo[l,2-b]pyridazin- 3-yl]pentanoate NMR (CDC13, 5): 1.23 (3H, t, J=7Hz), 134-1.55 (7H, m), 2.11 -2.22 (5H, m), 2.47 (2H,m), 3.02 (2H,q, J=7Hz), 4.09 (2H, q, J=7Hz), 5.29 (2H,s), 5.94 (lH,d, J=5Hz), 6.63 (1H, d, J=5Hz), 7.88 (1H, m), 8.56 (1H, m), 8.79 (1H, m) Example 76 To a solution of ethyl 5-[4-(3-cyanophenyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate (1.20 g) in ethanol (12 mL) was added IN sodium hydroxide (4.62 mL) and was stirred at ambient temperature for 2 hours. The reaction mixture was acidified with IN hydrogen chloride and was partitined between ethyl acetate and water. The organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by flash silica gel chromatography (silica gel, 100 mL) eluted with hexane-ethyl acetate= 3-1,2-1, and 1-1 to give an yellow solid (846 mg). The solid was recrystallized from hexane-ethyl acetate (5-1) to give 5-[4-(3-cyanophenyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid as a pale yellow crystals (795 mg, 71.4%). 5-[4-(3-Cyanophenyl)-7-ethyl-2-melhylpyrrolo[l,2-b]pyridazin-3-yl]penlanoic acid mp: 109-110°C NMR (CDC13,6): 1.33-1.60 (7H, m), 2.42 (2H, t, J=8Hz), 2.34-2.48 (2H, m), 2.56 (3H, s), 3.01 (2H, q, J=8Hz), 5.80 (1H, d, J=5Hz), 6.52 (1H, d, J=5Hz), 7.56-7.64 (2H, m), 7.66 (1H, br s), 7.76 (1H, m) MS (ES1+): m/z 362 (M-H) The following compounds were obtained in substantially the same manner as that of Example 76. Example 77 3-[4-(3-Chlorophenyl)-7-ethyl-2-phenylpynolo[l,2-b]pyridazin-3-yl]propanoicacid NMR (CDC13,5): 1.36 (3H, t, J=7 H), 1.56 (2H, m), 2.03 (2H, m), 2.79 (2H, m), 3.01 (2H, q, J=7Hz), 6.01 (1H, d, J=5Hz), 6.63 (1H, d, J=5Hz), 7.27 (1H, m), 7.40-7.53 (8H,m) Example 78 5-{7-Ethyl-2-methyl-4-[3-(trifluoromethyl)phenyl]pyrrolo[l,2-b]pyridazin-3-yljpentanoic acid NMR (CDCI3, 5): 1.37 (3H, t, J=7Hz), 1.40-1.62 (4H, m), 2.22 (2H, t, J=7Hz), 2.38- 2.46 (2H, m), 2.56 (3H, s), 3.02 (2H, q, J=7Hz), 5.84 (1H, d, J=4Hz), 6.51 (1H, d, J=4Hz), 7.53-7.64 (3H, m), 7.72 (1H, d, J=8Hz) MS (ESI+): m/z 403 (M-H), 405 (M+H) Example 79 5-[7-Ethyl-2-methyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoicacid NMR (CDCI3, 5): 1.37 (3H, t, J=7Hz), 1.45-1.67 (4H, m), 2.22 (2H, t, J=7Hz), 2.42 (3H, s), 2.35-2.48 (2H, m), 2.56 (3H, s), 3.02 (2H, q, J=7Hz), 5.83 (1H, d, J=4Hz), 6.51 (1H, d, J=4Hz), 7.53 (1H, s), 8.39 (1H, s), 8.53 (1H, s) MS (ES1+): m/z 352 (M+H) Example 80 5-[7-Eihyl-4-(3-methoxy-5-isoxazo]y])-2-(methoxymelhy])pyrrolo[l,2-b]pyrida2in-3-IJpentanoic acid NMR (CDCI3, 5): 1.36 (3H, 1, J=7Hz), 1.58-1.83 (4H,m), 2.38 (2H, t, J=7Hz), 2.74- 2.85 (2H, m), 3.03 (2H, q, J=7Hz), 3.43 (3H, s), 4.08 (3H, s), 4.62 (2H, s), 6.28 (1H, s), 6.41 (1H, d, J=4Hz), 6.67 (1H, d, J=4Hz) MS (ES1+): m/z 386 (M-H), 388 (M+H) Example 81 5-{7-Ethyl-2-methyl-4-[3-(l,3-oxazol-5-yl)phenyl]pyrrolo[l,2-b]pyridazin-3-yljpentanoic acid NMR (CDCI3, 5): 1.38 (3H, t, J=7Hz), 1.45-1.65 (4H, m), 2.21 (2H, t, J=7Hz), 2.43- 2.53 (2H, m), 2.56 (3H, s), 3.03 (2H, q, J=7Hz), 5.89 (1H, d, J=4Hz), 6.51 (1H, d, J=4Hz), 7.32 (1H, d, J=8Hz), 7.39 (1H, s), 7.53 (1H, t, J=8Hz), 7.65 (1H, s), 7.73 (lH,d,J=8Hz),7.93(lH,s) MS (ES1+): m/z 402 (M-H), 404 (M+H) Example 82 5-[4-(3,4-Dichlorophenyl)-7-elhyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoicacid NMR(CDC13,8): 1.37 (3H, t, J=7Hz), 1.42-1.65 (4H, m), 2.27 (2H, t,J=7Hz), 2.38- 2.48 (2H, m), 2.54 (3H, s), 3.02 (2H, q, J=7Hz), 5.87 (1H, d, J=4Hz), 6.51 (1H, d, J=4Hz), 7.19 (1H, dd, J=2 Hz, 8Hz), 7.45 (1H, d, J=2Hz), 7.56 (1H, d, J=8Hz) MS (ES1+): m/z 403 (M-H), 405 (M+H) Example 83 5-[4-(4-Chloro-2-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoicacid NMR (CDCI3, 5): 1.36 (3H,t, J=7Hz), 1.47-1.66 (4H,m),2.24 (2H, t, J=7Hz), 1.45- 2.56 (2H, m),2.55 (3H, s), 3.00 (2H, q, J=7Hz), 5.94 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 7.39 (1H, dd, J=2 Hz, 7Hz), 7.53 (1H, d, J=2Hz), 8.67 (1H, d, J=7Hz) MS (ESI+): m/z 372 (M+H) Example 84 5-[4-(5-Chloro-2-thienyl)-7-elhy]-2-(methoxymcthyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3, 5): 1.36 (3H, l, J=7Hz), 1.52-1.74 (4H, m), 2.33 (2H, 1, J=7Hz), 2.69- 2.78 (2H, m), 3.01 (2H, q, J=7Hz), 3.44 (3H, s), 4.60 (2H, s), 6.25 (1H, d, J=4Hz), 6.60 (1H, d, J=4Hz), 6.97 (2H, m) MS (ESI+): m/z 405 (M-H), 407 (M+H) Example 85 5-[7-Ethyl-4-(6-methoxy-2-pyrazinyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3, 8): 1.37 (3H, t, J=7Hz), 1.55-1.69 (4H, m), 2.28 (2H, m), 2.52 (2H, m), 2.56 (3H, s), 3.03 (2H, q, J=7Hz), 3.97 (3H, s), 6.03 (1H, d, J=4Hz), 6.54 (1H, d, J=4Hz), 8.30 (1H, s), 8.32 (1H, s) MS (ESI+): m/z 369 (M+H) Example 86 5-[4-(l-Benzofuran-2-yl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3, 8): 1.39 (3H, t, J=7Hz), 1.66-1.86 (4H, m), 2.34-2.47 (2H, m), 2.58 (3H, s), 2.69-2.85 (2H, m), 3.03 (2H, q, J=7Hz), 6.47 (1H, d, J=4Hz), 6.61 (1H, d, J=4Hz), 7.16 (1H, s), 7.26-7.43 (2H, m), 7.57 (1H, d, J=8Hz), 7.68 (1H, d, J=8Hz) Example 87 5-[4-(l-Benzothien-2-yl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3,8): 1.37 (3H, t, J=7Hz), 1.53-1.73 (4H, m), 2.30 (2H, t, J=7Hz), 2.56 (3H, s), 2.62-2.73 (2H, m), 3.02 (2H, q, J=7Hz), 6.19 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 7.34-7.45 (3H, m), 7.79-7.93 (2H, m) Example 88 5-[7-Ethyl-2-methyl-4-(l,3-oxazol-5-yl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoicacid NMR (CDCI3,8): 1.37 (3H, 1, J=7Hz), 1.57-1.70 (2H, m), 1.70-1.88 (2H, m), 2.43 (2H, t, J=7Hz), 2.56 (3H, s), 2.66-2.75 (2H, m), 3.02 (2H, q, J=7Hz), 6.41 (1H, d, J=4Hz), 6.60 (1H, d, J=4Hz), 7.52 (1H, s), 8.13 (1H, s) MS (ESI+): m/z 328 (M+H) Example 89 5-(7-Ethyl-2-methyl-4-phenylpyrrolo[l,2-b]pyridazin-3-yI)pentanoic acid NMR (CDC13, 8): 1.37 (3H, t, J=7Hz), 1.40-1.62 (4H, m), 2.20 (2H, t, J=7Hz), 2.43- 2.52 (2H, m), 2.54 (3H, s), 3.01 (2H, q, J=7Hz), 5.89 (1H, d, J=4Hz), 6.48 (1H, d, J=4Hz), 7.33 (2H, m), 7.38-7.52 (3H, m) MS (ESI+): m/z 337 (M+H) Example 90 5-[7-Ethyl-2-methyl-4-(6-quinolinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3,5): 1.39 (3H, t, J=7Hz), 1.47-1.61 (4H, m), 2.14-2.23 (2H, m), 2.44- 2.55 (2H, m), 2.59 (3H, s), 3.05 (2H, q, J=7Hz), 5.86 (1H, d, J=4Hz), 6.51 (1H, d, J=4Hz), 7.49 (1H, m), 7.73 (1H, dd, J=2 Hz, 8Hz), 7.85 (1H, d, J=2Hz), 8.23 (2H, m),8.97(lH,m) MS (ESI+): m/z 386 (M-H), 388 (M+H) Example 91 7-{4-[4-(Aminosulfonyl)phenyl]-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl}heptanoic acid NMR (CDCI3, 5): 0.98 (2H, m), 1.17-1.48 (9H, m), 2.27 (2H, t, J=7Hz), 2.36 (2H, m), 2.56 (3H, s), 3.02 (2H, q, J=7Hz), 5.06 (2H, s, br), 5.84 (1H, d, J=5Hz), 6.52 (1H, d, J=5Hz), 7.52 (2H, d, J=9Hz), 8.04 (2H, d, J=9Hz) MS (ESJ+): m/z 444 (M+H) Example 92 ({[4-(3-Chlorophenyl)-7-ethyl-2-(2-furyl)pyrrolo[l,2-b]pyridazin-3-yl]carbonyl}amino)acetic acid NMR (CDCI3,6): 1.41 (3H, t, J=7Hz), 3.07 (2H, q, J=7Hz), 3.95 (2H, d, J=5Hz), 6.02 (1H, t, br, 5Hz), 6.37 (1H, d, J=5Hz), 6.50 (1H, m), 6.75 (1H, d, J=5Hz), 7.01 (1H, d, J=7Hz), 7.37-7.45 (3H, m), 7.51 (1H, m), 7.55 (1H, m) Example 93 5-{7-Ethyl-2-methyl-4-[3-(methylsulfonyl)phenyI]pyrrolo[l,2-b]pyriciazin-3-y]}pentanoic :id NMR (CDC13,5): 1.30-1.59 (7H, m), 2.22 (2H, t, J=8Hz), 2.33-2.49 (2H, m), 2.56 (3H, s), 3.01 (2H, q, J=8Hz), 3.12 (3H, s), 5.80 (1H, d, J=5Hz), 6.50 (1H, d, J =5Hz), 7.63-7.74 (2H, m), 7.95 (1H, br s), 8.03 (1H, br d, J=8Hz) MS (ES1+): m/z 415 (M+H) Example 94 5-[4-(2-Chloro-4-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid mp: 139-140°C NMR (CDC13,8): 1.32-1.64 (7H, m), 2.28 (2H, t, J=8Hz), 2.36-2.46 (2H, m), 2.55 (3H, s), 3.00 (2H, q, J=8Hz), 5.85 (1H, d, J=5Hz), 6.52 (1H, d, J=5Hz), 7.24 (1H, br d, J=7Hz), 7.36 (1H, br s), 8.53 (1H, d, J=7Hz) MS (ES1+): m/z 372 (M+H) Example 95 5-[7-Ethyl-2-methyl-4-(2-vinyl-4-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoicacid NMR (CDC13,8): 1.36 (3H, t, J=8Hz), 1.40-1.62 (4H, m), 2.25 (2H, t, J=8Hz), 2.35- 2.47 (2H, m), 2.56 (3H, s), 3.00 (2H, q, J=8Hz), 5.54 (1H, d, J=10Hz), 5.86 (1H, d, J=5Hz), 6.23 (1H, d, J=16Hz), 6.51 (1H, d, J=5Hz), 6.88 (1H, dd, J=16,10Hz), 7.20 (1H, dd, J=6,1Hz), 7.38 (1H, br s), 8.70 (1H, d, J=6Hz) Example 96 5-[7-Ethy]-2-methyl-4-(3-nitrophenyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoicacid NMR (CDCI3,8): 1.37 (3H, t, J=8Hz), 1.41-1.59 (4H, m), 2.23 (2H, t, J=8Hz), 2.37- 2.47 (2H, m), 2.57 (3H, s), 3.02 (2H, q, J=8Hz), 5.81 (1H, d, J=5Hz), 6.51 (1H, d, J=5Hz), 7.63-7.74 (2H, m), 8.25 (1H, br s), 8.32 (1H, m) Example 97 {[7-Ethyl-4-(4-fluorophenyl)-2-isopropylpyrroIo[l,2-b]pyridazin-3-y]]rnethoxy} acetic acid NMR (CDCI3, 5): 1.33-1.45 (9 H, m), 3.04 (2H, q, J=8Hz), 3.43 (1H, m), 4.01 (2H, s), 4.45 (2H, s), 6.09 (1H, d, J=5Hz), 6.58 (1H, d, J=5Hz), 7.13-7.22 (2H, m), 7.40-7.49 (2H,m) Example 98 5-[4-(5-Acetyl-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3, 5): 1.37 (3H, t, J=7Hz), 1.43-1.63 (4H, m), 2.23 (2H, t, J=7Hz), 2.35- 2.48 (2H, m), 2.57 (3H, s), 2.69 (3H, s), 3.03 (2H, q, J=7Hz), 5.80 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 8.26 (1H, m), 8.78 (1H, d, J=2Hz), 9.23 (1H, d, J=2Hz) MS: (m/z) 378 (M-H), 380 (M+H) Example 99 5-{4-(2-Chloro-4-pyridinyl)-7-ethyl-2-[(methylthio)methyl]pyrrolo[l,2-b]pyridazin-3-yl}pentanoic acid NMR (CDCI3, 5): 1.36 (3H, t, J=7Hz), 1.42-1.65 (4H, m), 2.18 (3H, s), 2.28 (2H, t, J=7Hz), 2.48-2.60 (2H, m), 3.02 (2H, q, J=7Hz), 3.81 (2H, s), 5.89 (1H, d, J=4Hz), 6.57 (1H, d, J=4Hz), 7.27 (1H, m), 7.38 (1H, s), 8.53 (1H, d, J=5Hz) MS: (m/z) 416 (M-H), 418 (M+H) Example 100 5-{4-(2-Chloro-4-pyridinyl)-7-ethyl-2-[(methylsulfonyl)methyl]pyrrolo[l,2-b]pyridazin-3-yl}pentanoic acid NMR (CDCI3, 5): 1.37 (3H, t, J=7Hz), 1.45-1.65 (4H, m), 2.29 (2H, t, J=7Hz), 2.56- 2.67 (2H, m), 2.98 (2H, q, J=7Hz), 3.13 (3H, s), 4.54 (2H, s), 5.98 (1H, d, J=4Hz), 6.69 (1H, d, J=4Hz)5 7.27 (1H, m), 7.38 (1H, s), 8.56 (1H, d, J=5Hz) MS: (m/z) 448 (M-H), 450 (M+H) Example 101 5-[4-(2-Chloro-4-pyridinyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]penlanoicacid NMR (CDCI3,5): 1.03-1.45 (4H, m), 1.36 (3H, t, J=7Hz), 1.97 (2H, t, J=7Hz), 2.36-2.48 (2H, m), 3.02 (2H, q, J=7Hz), 5.96 (1H, d, J=4Hz), 6.64 (1H, d, J=4Hz), 7.31 (1H, d, J=5Hz), 7.39-7.53 (6H, m), 8.55 (1H, d, J=5Hz) Example 102 5-[4-(6-Chloro-2-pyridinyl)-7-elhyl-2-methylpyrrolo-[l,2-b]pyridazin-3-y]]pentanoicacid NMR (CDC13,5): 1.36 (3H, t, J=7Hz), 1.56-1.73 (4H, m), 2.29 (2H, t, J=7Hz), 2.46- 2.56 (2H, m), 2.56 (3H, s), 3.02 (2H, q, J=7Hz), 5.96 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 7.38-7.48 (2H, m), 7.78 (1H, t, J=8Hz) MS (ES1+): m/z 372 (M+H), MS (ESI"): m/z 370 Example 103 5-[7-Ethyl-4-(3-methoxyphenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3,5): 1.37 (3H, t, J=7Hz), 1.46-1.63 (4H, m), 2.22 (2H, t, J=7Hz), 2.44- 2.53 (2H, m), 2.54 (3H, s), 3.01 (2H, q, J=7Hz), 3.82 (3H, s), 5.92 (1H, d, J=4Hz), 6.49 (1H, d, J=4Hz), 6.87-7.01 (3H, m), 7.37 (1H, t, J=8Hz) MS (ESI+): m/z 367, MS (ESI): m/z 365 Example 104 5-[4-(3,5-Dichlorophenyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoicacid NMR (CDCI3,8): 1.37 (3H, t, J=7Hz), 1.42-1.53 (2H, m), 1.53-1.66 (2H, m), 2.27 (2H, t, J=7Hz), 2.41-2.49 (2H, m), 2.54 (3H, s), 3.01 (2H, q, J=7Hz), 5.88 (1H, d, J=4Hz), 6.52 (1H, d, J=4Hz), 7.26 (2H, m), 7.45 (1H, m) MS (ESI+): m/z 405, MS (ESI): m/z 403 Example 105 5-[4-(5-Chloro-2-thienyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoicacid NMR (CDCI3,8): 1.36 (3H, t, J=7Hz), 1.48-1.62 (2H, m), 1.62-1.73 (2H, m), 2.34 (2H, t, J=7Hz), 2.53 (3H, s), 2.58-2.67 (2H, m), 2.99 (2H, q, J=7Hz), 6.20 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 6.94 (1H, d, J=4Hz), 6.98 (1H, d, J=4Hz) MS (ESI+): m/z 377, MS (ESI"): m/z 375 Example 106 5-[7-Ethyl-4-(3-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoicacid NMR (CDCI3,5): 1.37 (3H, t, J=7Hz), 1.40-1.64 (4H, m), 2.23 (2H, t, J=7Hz), 2.41- 2.49 (2H, m), 2.55 (3H, s), 3.00 (2H, q, J=7Hz), 5.88 (1H, d, J=4Hz), 6.50 (1H, d, J=4Hz), 7.03-7.16 (3H, m), 7.38-7.47 (1H, m) MS (ES1+): m/z 355, MS (ESI"): m/z 353 Example 107 5-[7-Ethyl-2-methyl-4-(3-quinolinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3,5): 1.39 (3H, t, J=7Hz), 1.47-1.65 (4H, m), 2.20-2.30 (2H, m), 2.45- 2.53 (2H, m), 2.59 (3H, s), 3.05 (2H, q, J=7Hz), 5.87 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 7.62 (1H, t, J=8Hz), 7.79 (1H, t, J=8Hz), 7.87 (1H, d, J=8Hz), 8.21 (2H, m),8.88(lH,d,J=2Hz) MS (ESI+): m/z 388, MS (ESI"): m/z 386 Example 108 5-[7-Ethyl-2-methyl-4-(4-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3, 8): 1.37 (3H, t, J=7Hz), 1.40-1.70 (4H, m), 2.20-2.30 (2H, m), 2.37- 2.53 (2H, m), 2.56 (3H, s), 3.01 (2H, q, J=7Hz), 5.84 (1H, d, J=4Hz), 6.51 (1H, d, J=4Hz), 7.39 (2H, d, J=7Hz), 8.74 (2H, d, J=7Hz) Example 109 5-[7-Ethyl-4-(3-methoxy-5-isoxazolyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3, 8): 1.36 (3H, t, J=7Hz), 1.57-1.84 (4H, m), 2.41 (2H, t, J=7Hz), 2.55 (3H, s), 2.63-2.72 (2H, m), 3.02 (2H, q, J=7Hz), 4.08 (3H, s), 6.27 (1H, s), 6.34 (1H, d, J=4Hz), 6.57 (1H, d, J=4Hz) Example 110 5-[7-Ethyl-4-(3-methoxyphenyl)-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3,8): 1.06-1.33 (4H, m), 1.36 (3H, t, J=7Hz), 1.91 (2H, t, J=7Hz), 2.42- 2.53 (2H, m), 3.01 (2H, q, J=7Hz), 3.83 (3H, s), 6.03 (1H, d, J=4Hz), 6.59 (1H, d, J=4Hz), 6.93-7.02 (3H, m), 7.36-7.54 (6H, m) MS (ES1+): m/z 429 Example 111 5-[7-Ethy]-2-methyl-4-(5-methy]-3-isoxazo]yl)pyrrolo[l,2-b]pyridazin-3-)'l]pentanoic acid NMR (CDCI3,5): 1.36 (3H, I, J=7Hz), 1.52-1.77 (4H, m), 2.35 (2H, t, J=7Hz), 2.55 (6H, s), 2.56-2.67 (2H, m), 3.01 (2H, q, J=7Hz), 6.16 (1H, d, J=4Hz), 6.23 (1H, s), 6.54(lH,d,J=4Hz) MS (ESI+): m/z 342, MS (ESI"): m/z 340 Example 112 5-[7-Ethyl-2-phenyl-4-(4-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoicacid NMR (CDCI3, 8): 1.11-1.33 (4H, m), 1.36 (3H, t, J=7Hz), 1.99 (2H, t, J=7Hz), 2.38- 2.50 (2H, m), 3.03 (2H, q, J=7Hz), 5.94 (1H, d, J=4Hz), 6.63 (1H, d, J=4Hz), 7.38-7.56 (7H, m), 8.74 (2H, d, J=6Hz) Example 113 5-[7-Ethyl-2-phenyl-4-(2-pyrazinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoicacid NMR (CDCI3, 5): 1.10-1.33 (4H, m), 1.36 (3H, t, J=7Hz), 1.95 (2H, t, J=7Hz), 2.45- 2.57 (2H, m), 3.02 (2H, q, J=7Hz), 6.05 (1H, d, J=4Hz), 6.66 (1H, d, J=4Hz), 7.40-7.55 (5H, m), 8.67 (1H, d, J=3Hz), 8.77 (1H, s), 8.85 (1H, s) MS (ESI+): m/z 401, MS (ESI): m/z 399 Example 114 5-[7-Ethyl-2-phenyl-4-(3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoicacid NMR (CDCI3, 8): 1.05-1.30 (4H, m), 1.36 (3H, t, J=7Hz), 1.95 (2H, t, J=7Hz), 2.35- 2.48 (2H, m), 3.02 (2H, q, J=7Hz), 5.94 (1H, d, J=4Hz), 6.62 (1H, d, J=4Hz), 7.40-7.55 (6H, m), 7.76-7.83 (1H, m), 8.65-8.72 (2H, m) MS (ESI+): m/z 400, MS (ESI"): m/z 398 Example 115 5-[4-(2-Chloro-4-pyridinyl)-7-ethyl-2-(methoxymethy])pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDC)3,5): 1.37 (3H, t, J=7Hz), 1.42-1.64 (4H, m), 2.27 (2H, t, J=7Hz), 2.48- 2.62 (2H, m), 3.04 (2H, q, J=7Hz), 3.45 (3H, s), 4.62 (2H, s), 5.90 (1H, d, J=4Hz), 6.61 (1H, d, J=4Hz), 7.27 (1H, m), 7.38 (1H, s), 8.53 (1H, d, J=5Hz) MS(ESI+):m/z402 Example 116 5-[7-Ethyl-2-(methoxymethyl)-4-(3-methoxyphenyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDC13, 5): 1.37 (3H, t, J=7Hz), 1.40-1.62 (4H, m), 2.19 (2H, t, J=7Hz), 2.55- 2.66 (2H, m), 3.03 (2H, q, J=7Hz), 3.45 (3H, s),3.82 (3H, s), 4.62 (2H, s),5.96 (1H, d, J=4Hz), 6.56 (1H, d, J=4Hz), 6.87-7.00 (3H, m), 7.37 (1H, t, J=8Hz) MS (ES1+): m/z 397, MS (ESI"): m/z 395 Example 117 5-[4-(2-Chloro-4-pyridinyl)-7-ethyl-2-(2-thienyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3, 6): 1.20-1.50 (4H, m), 1.38 (3H, t, J=7Hz), 2.15 (2H, t, J=7Hz), 2.55- 2.68 (2H, m), 3.04 (2H, q, J=7Hz), 5.93 (1H, d, J=4Hz), 6.64 (1H, d, J=4Hz), 7.13 (1H, t, J=5Hz), 7.28 (1H, d, J=5Hz), 7.35-7.47 (3H, m), 8.54 (1H, d, J=5Hz) MS(ESI+):m/z440 Example 118 5-[7-Ethyl-2-(methoxymethyl)-4-(6-quinolinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3, 5): 1.39 (3H, t, J=7Hz), 1.45-1.60 (4H, m), 2.16 (2H, m), 2.55-2.75 (2H, m), 3.07 (2H, q, J=7Hz), 3.47 (3H, s), 4.66 (2H, s), 5.89 (1H, d, J=4Hz), 6.57 (1H, d, J=4Hz), 7.45-7.53 (1H, m), 7.72 (1H, d, J=8Hz), 7.86 (1H, s), 8.22 (2H,m),8.94(lH,m) MS (ES1+): m/z 418, MS (ESI"): m/z 416 Example 119 5-[7-Elhyl-2-(methoxymethyl)-4-(3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3,5): 1.38 (3H, t, J=7Hz), 1.45-1.64 (4H, m), 2.22 (2H, t, J=7Hz), 2.48- 2.68 (2H, m), 3.06 (2H, q, J=7Hz), 3.46 (3H, s), 4.63 (2H, s), 5.89 (1H, d, J=4Hz), 6.58 (1H, d, J=4Hz), 7.48 (1H, m), 7.78 (1H, m), 8.62 (1H, m), 8.69 (1H, m) MS (ESI+): m/z 368 Example 120 5-[4-(3-Chlorophenyl)-7-ethyl-2-(methoxymethyl)pyrro]o[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3,5): 1.37 (3H, t, J=7Hz), 1.45-1.63 (4H, m), 2.23 (2H, t, J=7Hz), 2.53- 2.63 (2H, m), 3.04 (2H, q, J=7Hz), 3.45 (3H, s), 4.63 (2H, s), 5.93 (1H, d, J=4Hz), 6.58 (1H, d, J=4Hz), 7.25 (1H, m), 7.36 (1H, s), 7.42 (2H, m) Example 121 5-[7-Ethyl-2-methyl-4-(3-methylphenyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3,5): 1.23-1.63 (4H, m), 1.37 (3H, t, J=7Hz), 2.22 (2H, t, J=7Hz), 2.40 (3H, s), 2.40-2.49 (2H, m), 2.54 (3H, s), 3.02 (2H, q, J=7Hz), 5.89 (1H, d, J=4Hz), 6.48 (1H, d, J=4Hz), 7.10-7.14 (2H, m), 7.23-7.27 (1H, m), 7.32-7.38 (1H, m) MS(ESI+):m/z351 Example 124 5-[7-Ethyl-2-(methoxymelhyl)-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3,5): 1.37 (3H, t, J=7Hz), 1.44-1.65 (4H, m), 2.16-2.26 (2H, m), 2.43 (3H, s), 2.47-2.69 (2H, m), 3.03 (2H, q, J=7Hz), 3.45 (3H, s), 4.63 (2H, m), 5.88 (1H, d, J=4Hz), 6.57 (1H, d, J=4Hz), 7.56 (1H, s), 8.42 (1H, s), 8.53 (1H, s) MS (ES1+): m/z 382,MS (ESI): m/z380 Example 125 5-[4-(5-Bromo-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoicacid NMR (CDCI3,5): 1.37 (3H, t, J=7Hz), 1.45-1.67 (4H, m), 2.27 (2H, l, J=7Hz), 2.38- 2.52 (2H, m), 2.56 (3H, s), 3.02 (2H, q, J=7Hz), 5.87 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 7.88 (1H, m), 8.53 (1H, d, J=2Hz), 8.77 (1H, d, J=2Hz) MS (ESI+):m/z 416,418 Example 126 5-[4-(5-Bromo-3-pyridiny])-7-ethyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3-yljpentanoic acid NMR (CDC13, 8): 1.37 (3H, t, J=7Hz), 1.45-1.65 (4H, m), 2.25 (2H, t, J=7Hz), 2.49- 2.68 (2H, m), 3.03 (2H, q, J=7Hz), 3.45 (3H, s), 4.63 (2H, s), 5.91 (1H, d, J=4Hz), 6.62 (1H, d, J=4Hz), 7.89 (1H, m), 8.51 (1H, s), 8.79 (1H, m) MS(ESI+):m/z446,448 Example 127 5-[4-(5,6-Dichloro-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3, 5): 1.37 (3H, t, J=7Hz), 1.43-1.68 (4H, m), 2.29 (2H, t, J=7Hz), 2.38- 2.52 (2H, m), 2.57 (3H, s), 3.02 (2H, q, J=7Hz), 5.87 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 7.81 (1H, d, J=2Hz), 8.31 (1H, d, J=2Hz) MS (ESI+): m/z 406, MS (ESI"): m/z 404 Example 128 5-[7-Ethyl-2-methyl-4-(5-vinyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3, 5): 1.37 (3H, t, J=7Hz), 1.45-1.68 (4H, m), 2.23 (2H, t, J=7Hz), 2.38- 2.53 (2H, m), 2.56 (3H5 s), 3.02 (2H, q, J=7Hz), 5.46 (1H, d, J=llHz), 5.86 (1H, d, J=4Hz), 5.89 (1H, d, J=17Hz), 6.52 (1H, d, J=4Hz), 6.72-6.83 (1H, dd, J=ll Hz, 17Hz), 7.77 (1H, m), 8.47 (1H, d, J=2Hz), 8.68 (1H, d, J=2Hz) MS (ES1+): m/z 364 Example 129 5-[7-Ethyl-2-(methoxymethyl)-4-(5-vinyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3, 5): 1.37 (3H, t, J=7Hz), 1.45-1.65 (4H, m), 2.22 (2H, t, J=7Hz), 2.45- 2.73 (2H, m), 3.04 (2H, q, J=7Hz), 3.46 (3H, s), 4.63 (2H, m), 5.44 (1H, d, J=llHz), 5.87 (1H, d, J=18Hz), 5.92 (1H, d, J=4Hz), 6.57 (1H, d, J=4Hz), 6.72-6.83 (1H, dd, J=l 1 Hz, 18Hz), 7.78 (1H, s), 8.48 (1H, s), 8.68 (1H, s) MS (ES1+): m/z 394 (M+H), MS (ESI"): m/z 392 Example 130 5-[4-(5-Acetyl-3-pyridinyl)-7-ethyl-2-(methoxymethyl)pyrro]o[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDC13,8): 1.38 (3H, t, J=7Hz), 1.44-1.60 (4H, m), 2.22 (2H, t, J=7Hz), 2.50- 2.63 (2H, m), 2.69 (3H, s), 3.02 (2H, q, J=7Hz), 3.46 (3H, s), 4.64 (2H, s), 5.86 (1H, d, J=4Hz), 6.59 (1H, d, J=4Hz), 8.29 (1H, m), 8.79 (1H, d, J=2Hz), 9.23 (1H, d,J=2Hz) MS (ESI+): m/z 410, MS (ESI): m/z 408 Example 131 4-[7-Ethyl-2-(methoxymethyl)-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]butanoic acid NMR (CDC13,5): 1.38 (3H, t, J=7Hz), 1.70-1.87 (2H, m), 2.26 (2H, t, J=7Hz), 2.45 (3H, s), 2.53-2.81 (2H, m), 3.06 (2H, q, J=7Hz), 3.46 (3H, s), 4.66 (2H, m), 5.90 (1H, d, J=4Hz), 6.59 (1H, d, J=4Hz), 7.61 (1H, s), 8.43 (1H, s), 8.46 (1H, s) MS(ESl+):m/z368 Example 132 3-[7-Ethyl-2-(methoxymethyl)-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]propanoic acid NMR (CDC13,5): 1.37 (3H, t, J=7Hz), 2.30-2.60 (2H, m), 2.42 (3H, s), 2.77-3.13 (2H, m), 3.05 (2H, q, J=7Hz), 3.47 (3H, s), 4.66 (2H, s), 5.91 (1H, d, J=4Hz), 6.60 (1H, d, J=4Hz), 7.58 (1H, s), 8.42 (1H, s), 8.54 (1H, s) MS (ESI+): m/z 354 Example 133 4-[7-Ethyl-2-methyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]butanoicacid NMR (CDCI3,5): 1.37 (3H, t, J=7Hz), 1.70-1.88 (2H, m), 2.22-2.32 (2H, m), 2.45 (3H, s), 2.50-2.62 (2H, m), 2.59 (3H, s), 3.02 (2H, q, J=7Hz),'5.86 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 7.60 (1H, s), 8.42 (2H, m) MS (ESI+): m/z 338, MS (ESI): m/z 336 Example 134 3-[7-Ethy]-2-methyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]propanoicacid NMR (CDC13, 6): 1.37 (3H, t, J=7Hz), 2.42 (3H, s), 2.40-2.53 (2H, m), 2.59 (3H, s), 2.82 (2H, 1, J=7Hz), 3.03 (2H, q, J=7Hz), 5.86 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 7.57 (1H, s), 8.38 (1H, s), 8.52 (1H, s) MS (ESI+): m/z 324, MS (ESI"): m/z 322 Example 135 3-[4-(5-Bromo-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]propanoic acid mp: 181-182°C NMR (CDC13, 5): 1.38(2H, t, J=7Hz), 2.4(2H, t, J=7Hz), 2.58(3H, s), 2.74-2.85(2H, m), 3.01(2H, q, J=7Hz), 5.89(1H, d, J=4Hz), 6.55(1H, d, J=4Hz), 7.87(1H, s), 8.54(lH,s),8.77(lH,s) MS: (m/z) 388 (M+), 390(M++2), 114(bp) Example 136 5-[4-(3-Cyanophenyl)-7-ethyl-2-(methoxymethyl)pyrroIo[l,2-b]pyridazin-3-yl]pentanoic acid NNMR (CDC13,5): 1.30-1.57 (5H, m), 2.21 (2H, t, J=8Hz), 2.47-2.57 (2H, m), 3.03 (2H, q, J=8Hz), 3.45 (3H, s), 4.62 (2H, s), 5.84 (1H, d, J=5Hz), 6.57 (1H, d, J=5Hz), 7.59-7.64 (2H, m), 7.68 (1H, br s), 7.75 (1H, m) MS (ESI): 392 (M+H) Example 136-2 5-[4-[3-(Aminocarbonyl)phenyl]-7-ethyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3-yljpentanoic acid NMR (CDCI3, 5): 1.30-1.70 (5H, overlappoed with H20), 2.20-2.50 (4H, m), 2.80- 2.93 (2H, m), 3.03 (2H, q, J=8Hz), 3.46 (3H, s), 4.54 (1H, d, J=10Hz), 4.77 (1H, d, J=10Hz), 5.80 (1H, d, J=5Hz), 6.55 (1H, d, J=5Hz), 7.43-7.50 (2H, m), 7.58 (1H, t, J=8Hz), 7.77 (1H, br s), 7.88 (1H, br s), 7.99 (1H, br d, J=8Hz) MS (ES1+): 410 (M+H) Example 137 5-[4-(5-Bromo-3-pyridinyl)-7-ethy]-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]penlanoicacid NMR (CDCI3,8): 1.06-1.26 (4H, m), 1.36 (3H, t, J=7Hz), 1.94 (2H, t, J=7Hz), 2.40 (2H, m), 2.99 (2H, q, J=7Hz), 5.96 (1H, d, J=5Hz), 6.63 (1H, d, J=5Hz), 7.40-7.52 (5H, m), 7.93 (1H, s), 8.59 (1H, s), 8.77 (1H, s) Example 138 5-[7-Ethyl-4-(5-ethyl-3-pyridinyl)-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]pentanoicacid NMR (CDCI3,5): 1.05-1.42 (10H, m), 1.92 (2H, m), 2.41 (2H, m), 2.75 (2H, q, J=7Hz), 3.01 (2H, q, J=7Hz), 5.93 (lH.'d, J=5Hz), 6.55 (1H, d, J=5Hz), 7.37-7.54 (5H, m), 7.62 (1H, m), 8.45 (1H, m), 8.52 (1H, m) Example 139 5-[4-(5-Bromo-3-pyridinyl)-7-ethyl-2-(2-thienyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3,5): 1.25-1.48 (7H, m), 2.12 (2H, t, J=7Hz), 2.62 (2H, m), 3.03 (2H, q, J=7Hz), 5.93 (1H, d, J=5Hz), 6.64 (1H, d, J=5Hz), 7.14 (1H, m), 7.37 (1H, d, J=5Hz), 7.43 (1H, d, J=5Hz), 7.92 (1H, s) 8.58 (1H, m), 8.79 (1H, m) MS(ESI+):m/z484(M+H) Example 140 5-[2-[(Benzyloxy)methyl]-4-(5-bromo-3-pyridinyl)-7-ethylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3,5): 1.23 (3H, t, J=7Hz), 1.34-1.48 (5H, m), 2.09 (2H, m), 2.53 (2H, m), 3.04 (2H, q, J=7Hz), 4.07 (2H, J=7Hz), 4.65 (2H, s), 4.72 (2H, s), 5.90 (1H, d, J=5Hz), 6.60 (1H, d, J=5Hz), 7.29-7.38 (5H, m), 7.86 (1H, s), 8.54 (1H, m), 8.77 (lH,m) Example 141 5-(4-(5-Bromo-3-pyridiny])-2-{[(4-cyanobenzyl)oxy]methyl}-7-ethy]pyrvolo[l,2-b]pyridazin-3-yl)pentanoic acid NMR (CDCI3,8): 1.35-1.56 (7H, m), 2.18 (2H, m), 2.57 (2H, m), 3.03 (2H, q, J=7Hz), 4.69 (2H, s), 4.74 (2H, s), 5.92 (1H, d, J=5Hz), 6.62 (1H, d, J=5Hz), 7.47 (2H, d, J=8Hz), 7.64 (2H, d, J=8Hz), 7.88 (1H, s), 8.54 (1H, m), 8.79 (1H, m) Example 142 5-[2-[(Benzylamino)methy]]-4-(5-bromo-3-pyridinyl)-7-ethy]pyrro]o[l32-b]pyridazin-3-yl]pentanoic acid NMR (CDC13, 8): 1.20-1.49 (7H, m), 2.17 (2H, m), 2.32 (2H, m), 3.04 (2H, q, J=7Hz), 4.29 (4H, s), 5.94 (1H, d, J=5Hz), 6.51 (1H, s, br), 6.12 (1H, d, J=5Hz), 7.27-7.36 (3H, m), 748 (2H, m), 7.84 (1H, m), 8.49 (1H, m), 8.75 (1H, m) Example 143 5-[4-(5-Bromo-3-pyridinyl)-7-ethyI-2-(4-morpholinylmethyl)pyrrolo[l,2-b]pyridazin-3-yljpentanoic acid NMR (CDC13,8): 1.20-1.38 (5H, m), 1.49 (4H, m), 2.24 (2H, q, J=7Hz), 2.59 (4H, m), 3.01 (2H, q, J=7Hz), 3.70 (4H, m), 5.88 (1H, d, J=5Hz), 6.55 (1H, d5 J=5Hz), 7.90 (1H, m), 8.55 81H, m), 8.78 (1H, m) Example 144 5-{4-[5-(Aminocarbonyl)-3-pyridiny]]-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yI}pentanoic acid from ethyl 5-[4-(5"Cyano-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]-pyridazin-3-yl]pentanoate NMR (CDC13, 5): 1.10-1.70 (4H, m), 1.37 (3H, t, J=7Hz), 2.24-2.77 (4H, m), 2.59 (3H, s), 3.02 (2H, q, J=7Hz), 5.77 (1H, d, J=4Hz), 6.52 (1H, d, J=4Hz), 7.57 (1H, br), 7.97 (1H, br), 8.07 (1H, s), 8.68 (1H, s), 9.18 (1H, s) MS(ESI+):m/z381 Example 145 5-[4-[5-(Aminocarbonyl)-3-pyridinyl]-7-ethyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3,5): 1.16-1.72 (4H, m), 1.37 (3H, t, J=7Hz), 2.25-2.50 (3H, m), 2.83- 2.97 (1H, m), 3.04 (2H, q, J=7Hz), 3.47 (3H, s), 4.56 (1H, d, J=17Hz), 4.77 (1H, d, J=17Hz),5.81 (1H, d, J=4Hz), 6.58 (1H, d, J=4Hz), 7.52 (1H, br), 7.82 (1H,br), 8.11 (1H, m), 8.70 (1H, d, J=2Hz), 918 (1H, d, J=2Hz) MS(ESI+):m/z411 Example 146 To a solution of triethyl 4-phosphonocrotonate (2.13 g) in tetrahydrofuran (20 nL) was added dropwise lithium bis(trimethylsilyl)amide (l.lmol/L solution in hexanes, 15mL) at 2°C under nitrogen, and the mixture was stirred at the same temperature for 30 minutes. To the mixture was added dropwise a solution of 4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazine-3-carbaldehyde (1.2 g) in tetrahydrofuran (20 mL). After being stirred for 3 hours at 2°C, the mixture was poured into saturated aqueous ammonium chloride, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (eluent; 3% ethyl acetate in n-hexane) to give the title compound (1.06 g) as an yellow crystals. Ethyl (2E,4E)-5-[4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazin-3-yl]-2,4-pentadienoate NMR (300 MHz, CDCI3,8): 1.28(3H, t, J=7Hz), 1.35(6H, d, J=7Hz), 3.30(1H, quintet, J=7Hz), 4.19(2H, quartet, J=7Hz), 5.63(1H, d, J=16Hz), 5.94QH, dd, J=16,HHz), 6.16(1H, dd, J=4.4,1.5Hz), 6.76(1H, dd, J-4.4,2.6Hz), 6.78(1H, d, J=16Hz), 7.11-7.23(3H, m), 7.33-7.40(2H, m), 7.72(1H, dd, J=2.6,1.5Hz) MS(ESI+):m/z379(M+H) The following compounds were obtained in substantially the same manner as that of Example 146. Example 147 Ethyl (2E)-3-[7-chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazin-3-yl]-2- propenoate NMR (CDC13, 6): 1.25 (3H, t, J=7Hz), 1.40 (6H, d, J=7Hz), 3.38 (1H, m), 4.16 (2H, q, J=7Hz), 5.57 (1H, d, J=15Hz), 6.25 (1H, d, J=5Hz), 6.74 (1H, d, J=5Hz), 7.15 (1H, d, J=8.5Hz), 7.29 (1H, d, J=8.5Hz), 733 (1H, d, J=8.5Hz), 7.35 (1H, d, J=8.5Hz), 7.63 (1H, d, J=15Hz) MS(ESI'):m/z385(M-H) Example 148 (2E)-3-[7-ChIoro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l>b]pyridazin-3-yl]-2- propenenitrile NMR (CDC13, 5): 1.41 (6H, d, J=7Hz), 3.28 (1H, m), 4.99 (1H, d, J=15Hz), 6.24 (1H, d, J=5Hz), 6.76 (1H, d, J=15Hz), 7.17-7.27 (2H, m), 7.30-7.40 (3H> m) MS (ESI"): m/z 340 (M+H) Example 149 To a solution of ethyl (2E,4E)-5-[4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazin-3-yl]-2,4-pentadienoate (300 mg) in tetrahydrofuran (3 mL) and acetic acid (lmL) was added dropwise N-chlorosuccinimide (106 mg). The mixture was stirred at ambient temperature for 24 hours. The resulting mixture was concentrated and partitioned between saturated aqueous sodium hydrogencarbonate and ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (eluent; 1% ethyl acetate in n-hexane) to give the title compound (HOmg) as an oil. Ethyl (2E,4E)-5-[7-chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazin-3-yl]-2,4-pentadienoate NMR (300 MHz, CDC13,8): 1.28(3H, t, J=7Hz), 1.40(6H, d, J=7Hz), 3.33(1H, quintet, J=7Hz), 4.19(2H, quartet, J=7Hz), 5.64(1 H, d, J=16Hz), 5.94(1H, dd, J=16,llHz), 6.18(1H, d, J=4.4Hz), 6.71(1H, d, J=4.4Hz), 6.79(1 H, d, J=16Hz), 7.13-7.23(3H, m), 7.32-7.37(2H, m) The following compounds were obtained in substantially the same manner as that of Example 149. Example 151 Ethyl 7-chloro-4-(2-chlorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazine-3-carboxylate NMR (300 MHz, CDCI3,8): 0.89 (3H, t, J=7.5Hz), 1.41 (6H, d, J=7.5Hz), 3.41-3.56 (1H, m), 4.00 (2H, q, J=7.5Hz)5 6.16 (1H, d5 J=5Hz), 6.76 (1H, d, J=5Hz), 7.25-7.53 (4H,m) MS (ES+);m/e 377.44 Example 152 Ethyl 7-ch]oro-2-isopropyl-4-(2-naphthyl)pyrrolo[l,2-b]pyridazine-3-carboxy]ate NMR (300 MHz, CDCI3,8): 0.78 (3H, t, J=7.5Hz), 1.43 (6H, d, J=7.5Hz), 3.29-3.41 (1H,m), 3.95 (2H, q, J=7.5Hz), 6.40 (1H, d, J=5Hz), 6.79 (1H,d, J=5Hz), 7.50-7.60 (3H, m), 7.81-8.00 (4H, m) Example 153 To a solution of ethyl (2E34E)-5-[7-chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l32-b]pyridazin-3-yl]-2,4-pentadienoate(82mg) in ethanol (2 mL) was added IN sodium hydroxide solution (0.5 mL), and the mixture was stirred at ambient temperature for 12 hours. The resulting mixture was concentrated in vacuo, and the residue was dissolved in water, acidified with IN hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (eluent; 50% ethyl acetate in n-hexane) to give the title compound (14mg) as a brown amorphous solid, which was recrystallized from aqueous ethanol. (2E,4E)-5-[7-Chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazin-3-yl]-2,4-pentadienoic acid NMR (300 MHz, CDCI3, 8): 1.40 (6H, d, J=7Hz), 1.30-1.90 (lH.br), 3.34 (1H, quintet, J=7Hz), 5.64 (1H, d, J=16Hz), 5.98 (1H, dd, J=16,llHz), 6.19 (1H, d, J=4.4Hz), 6.72 (1H, d, J=4.4Hz), 6.84 (1H, d, J=16Hz), 7.14-7.37 (5H, m) MS(ES1+): m/z 383 (M-H) Example 154 To a mixture of ethyl 5-[4-(2-chloro-4-pyridinyl)-7-ethyl-2-(2-thienyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate (130 mg) in toluene (5 mL) was added 28% sodium netbylate metanol solution (536 mg) and the mixture was healed under reflux for 2 hours. The solution was acidified to pH 4 with IN hydrochloric acid and extracted with chloroform. The organic layer was separated, dried over magnesium sulfate, and evaporated in vacuo. To the residue in ethanol (5 mL) was added IN sodium hydroxide solution (1 mL) and the mixture was heated at 60°Cfor 1 hour. The solution was acidified to pH 4 with IN hydrochloric acid and extracted with chloroform. The organic layer was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and ethyl acetate (1:1) to give 5-[7-ethyl-4-(2-methoxy-4-pyridinyl)-2-(2-thienyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid as an yellow powder (50.0 mg). 5-[7-Ethyl-4-(2-methoxy-4-pyridinyl)-2-(2-thienyl)pyrrolo[l,2-b]pyridazin-3-yljpentanoic acid NMR (CDC13, 5): 130-1.48 (4H, m), 1.38 (3H, t, J=7Hz), 2.13 (2H, t, J=7Hz), 2.58- 2.69 (2H, m), 3.02 (2H, q, J=7Hz), 4.02 (3H, s), 5.96 (1H, d, J=4Hz), 6.61 (1H, d, J=4Hz), 6.78 (1H, s), 6.90 (1H, d, J=5Hz), 7.12 (1H, m), 7.34 (1H, m), 7.42 (1H, d, J=5Hz), 8.29 (IH, d, J=5Hz) The following compounds were obtained in substantially the same manner as that of Example 354. Example 155 5-[7-Ethyl-4-(2-methoxy-4-pyridinyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3, 5): 1.31-1.64 (7H, m), 2.25 (2H, t, J=8Hz), 2.43 (2H, br t, J=8Hz), 2.54 (3H, s), 3.00 (2H, q, J=8Hz), 4.04 (3H, s), 5.60 (IH, br s), 5.90 (IH, d, J=5Hz), 6.51 (IH, d, J=5Hz), 6.81 (IH, br s), 6.93 (IH, br d, J=7Hz), 830 (IH, d, J=7Hz) MS(ESl+):m/z368(M+H) Example 155-2 5-[7-Ethyl-2-methyl-4-(2-oxo-l,2-dihydro-4-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yljpentanoic acid NMR (CDC13, 8); 1.29-1.67 (7H, m), 2.29 (2H, t, J=8Hz), 235-2.60 (5H, m), 3.00 (2H, q, J=8Hz), 5.94 (1H, d, J=5Hz), 6.54 (1H, d, J=5Hz), 6.64 (1H, br d, J=7Hz), 6.84 (1H, br s), 7.70 (1H, br d, J=7Hz) MS (ESI+): m/z 354 (M+H) The following compounds were obtained in substantially the same manner as that of Example 154. Example 156 5-[7-Ethyl-4-(2-methoxy-4-pyridinyl)-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDC13,5): 1.08-1.30 (4H, m), 1.36 (3H, t, J=7Hz), 1.95 (2H, t, J=7Hz), 2.48- 2.53 (2H, m), 3.03 (2H, q, J=7Hz), 4.01 (3H, s), 6.02 (1H, d, J=4Hz), 6.63 (1H, d, J=4Hz), 6.82 (1H, s), 6.94 (1H, d, J=5Hz), 7.42-7.54 (5H, m), 8.29 (1H, d, J=5Hz) MS(ESI+):m/z430 Example 157 5-[7-Ethyl-2-(methoxymethyl)-4»(2-methoxy-4-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3,5): 1.37 (3H, t, J=7Hz), 1.40-1.64 (4H, m), 2.24 (2H, t, J=7Hz), 2.53- 2.64 (2H, m), 3.03 (2H, q, J=7Hz), 3.45 (3H, s), 4.01 (3H, s), 4.61 (2H, s), 5.94 (1H, d, J=4Hz), 6.58 (1H, d, J=4Hz), 6.77 (1H, s), 6.89 (1H, d, J=5Hz), 8,28 (1H, d,J=5Hz) MS (ESI+): m/z398,MS (ESI): m/z 396 Example 158 To a solution of ethyl 5-[4-(2-chloro-4-pyridinyl)-7-ethyl-2-phenylpyrrolo[l,2-b)pyridazin-3-yl]pentanoate (120 mg) in toluene (5 mL) and leirahydrofuran (10 mL) was added sodium thiomethoxide (91.0 mg) and the mixture was heated under reflux for 4 hours. The solution was acidfied with IN hydrochloric acid and extracted with chloroform. The organic layer was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and ethyl acetate (10:1 - 3:1) to give 5-{7-ethyl-4-[2-(methylthio)-4-pyridinyl]-2-phenylpyrroIo-[l,2-b]pyridazin-3-yl}pentanoic acid as an yellow powder (85.0 mg). 5-{7-Ethyl-4-[2-(methylthio)-4-pyridinyl]-2-phenylpyrrolo[l52-b]pyrida2in-3-yl}pentanoic acid NMR(GDa3,8):1.07-117(2H,m),1.17-130(2H,m),136(3H,t,J=7Hz)>1.97 (2H,t, J=7Hz), 2.38-2.48 (2H, m), 2.61 (3H, s), 3.02 (2H, q, J=7Hz), 5.98 (1H, d, J=4Hz), 6.63 (1H, d, J=4Hz), 7.03 (1H, dd, J=l Hz, 5Hz), 7.25 (1H, m), 7.43-7.55 (5H,m),8.57(lH,d,J=5Hz) MS (ESf ): m/z 446 (M+H) Example 159 A mixture of 3-[(l-amino-5-ethyl-lH-pynol-2-yl)carbonyl]benzonitrile (3.00 g), ethyl 6-benzoylhexanoate (5.07 g), and trifluoromethanesulfonic acid (376 mg) in toluene (60 mL) was refluxed for 1 hour and 20 minutes with Dean-Stark equipment. The mixture was partitioned between ethy] acetate (60 mL) and water (60 mL), and the organic layer was washed with saturated sodium bicarbonate (60 mL) and brine (60 mL), dried over magnesium sulfate, and evaporated to give a dark colored oil. Flash silica gel column chromatography eluting with acetone = 1-100 to 7-100 afforded ethyl 5-[4-(3-cyanophenyl)-7-ethyl-2-phenylpyrrolo-[l,2-b]pyridazin-3-yl]pentanoate as an orange oil (4.45 g, 78.6%). Ethyl 5-[4-(3-cyanophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDC13, 5): 1.01-1.27 (7H, m), 1.36 (3H, t, J=7Hz), 1.86 (2H, t, J=7Hz), 2.40 (2H, m), 3.02 (2H, q, J=7Hz), 4.02 (2H, q, J=7Hz), 5.90 (1H, d, J=5Hz), 6.61 (1H, d, J=5Hz), 7.44-7.53 (5H, s), 7.60-7.69 (2H, m), 7.74-7.79 (2H, m) The following compound was obtained in substantially the same manner as that of Example 159. Example 160 Ethyl 5-[4-(2-chloro-4-pyridinyl)-7-ethyl-2-(2-thienyI)pyrrolo[l,2-b]pyridazin-3- yljpentanoale NMR (CDCI3,5): 1.21 (3H, t, J=7Hz), 1.38 (3H, t, J=7Hz), 1.25-1.48 (4H, m), 2.07 (2H, I, J=7Hz), 2.57-2.68 (2H, m), 3.04 (2H, q, J=7Hz), 4.12 (2H, q, J=7Hz),5.93 (1H, d, J=4Hz), 6.64 (1H, d, J=4Hz), 7.12 (1H, m), 7.28 (1H, dd, J=l Hz, 5Hz), 7.37 (1H, m), 7.41 (1H, s), 7.45 (1H, d, J=5Hz), 8.55 (1H, d, J=5Hz) MS: (m/z) 468 (M+H) Example 161 Ethyl 5-[4-(2-chloro-4-pyridinyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3- yljpentanoate NMR (CDCI3,5): 1.05-1.17 (2H, m), 1.19-1.30 (2H, m), 1.28 (3H, t, J=7Hz), 1.36 (3H, t, J=7Hz), 1.91 (2H, t, J=7Hz), 2.38-2.48 (2H, m), 3.02 (2H, q, J=7Hz), 4.12 (2H, q, J=7Hz), 5.96 (1H, d, J=4Hz), 6.64 (1H, d, J=4Hz), 7.31 (1H, dd, J=2 Hz, 5Hz), 7.41-7.54 (6H, m), 856 (1H, d, J=5Hz) MS (ESI+): m/z 462 (M+H) Example 162 Ethyl [4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-y]]acetate NMR (CDCI3,5): 1.08 (3H, t, J=7Hz), 137 (3H, t, J=7Hz), 3.03 (2H, q, J=7Hz), 3.36 (2H, s), 3.93 (2H, q, J=7Hz), 6.09 (1H, d, J=5Hz), 6.66 (1H, d, J=5Hz), 7.33 (1H, m), 7.41-7.50 (8H,m) MS (ESI+): m/z 419 (M+H) Example 163 Ethyl 4-(3-chlorophenyl)-7-ethyl-2-(2-furyl)pyrrolo[l,2-b]pyridazine-3-carboxylate NMR (CDCI3, 5): 1.06 (3H, t, J=7Hz), 1.41 (3H, t, J=7Hz), 3.08 (2H, q, J=7Hz), 4.09 (2H, q, J=7Hz), 6.34 (1H, d, J=5Hz), 6.53 (1H, m), 6.74 (1H, d, J=5Hz), 6.97 (1H, m), 7.39-7.46 (3H, m), 752 (2H, m) MS (ESI+): m/z 395 (M+H) Example 164 Ethyl 4-(3-chlorophenyl)-7-ethyl-2-(2-pyridinyl)pyrrolo[l,2-b]pyridazine-3-carboxylate NMR (CDCI3, 8): 0.94 (3H, m), 1.41 (3H, m), 3.08 (2H, q, J=7Hz), 3.11 (2H, m), 4.00 (2H, m), 6.36 (1H, m), 6.76 (1H, m), 7.26-7.55 (4H, m), 7.84 (1H, m), 8.15 (lH,m),8.57(lH,m) MS (ESI+): m/z 406 (M+H) Example 165 Ethyl 5-[4-(3-cyanophenyl)-7-ethyl-2-(l ,3-thiazol-2-yl)pynolo[l,2-b]pyridazin-3- yljpentanoate NMR (CDC13,8): 1.21 (3H, t, J=7Hz), 1.33-1.50 (7H, m), 2.14 (2H, t, J=7Hz), 2.46 (2H, m), 2.97 (2H, q, J=7Hz), 3.06 (2H, q, J=7Hz), 4.05 (2H, q, J=7Hz),5.88 (1H, d, J=5Hz), 6.67 (1H, d, J=5Hz), 7.43 (1H, d, J=3Hz), 7.64-7.67 (2H, m), 7.70 (1H, m), 7.78 (1H, m), 7.93 (1H, d, J=3Hz) Example 166 Methyl 5-[4-(3-cyanophenyl)-7-ethyl-2-(l-methyl-lH-pyrrol-2-yl)pyrrolo[l,2- b]pyridazin-3-yl]pentanoate NMR (CDC13,8): 1.04 (2H, m), 1.21-1.41 (5H, m), 1.99 (2H, t, J=7Hz), 2.46 (2H, m), 3.02 (2H, q, J=7Hz), 3.60 (3H, s), 3.68 (3H, s), 5.89 (1H, d, J=5Hz), 6.23 (1H, m), 6.35 (1H, m), 6.62 (1H, d, J=5Hz), 6.76 (1H, m), 7.62-7.79 (4H, m) Example 167 Ethyl 3-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]propanoate NMR (CDCI3,8): 1.08 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 2.02 (2H, m), 2.80 (2H, m), 3.02 (2H, q, J=7Hz), 3.89 (2H, q, J=7Hz), 6.01 (1H, d, J=5Hz), 6.63 (1H, d, J=5Hz), 7.31 (1H, m), 7.41-7.54 (8H, m) Example 168 Ethyl 5-[4-(3-cyanophenyl)-7-ethyl-2-(l,3-oxazol-5-yl)pyrrolo[l,2-b]pyridazin-3- yl]pentanoate NMR (CDCI3,8): 1.17-1.49 (10H, m), 2.08 (2H, t, J=7Hz), 2.57 (2H, m), 3.03 (2H, q, J=7Hz), 4.06 (2H, q, J=7Hz), 5.91 (1H, d, J=5Hz), 6.66 (1H, d J=5Hz), 7.55 (1H, s), 7.62-7.68 (3H, m), 7.78 (1H, m), 8.04 (1H, s) Example 169 Ethyl 5-[7-ethyl-4-(3-methoxyphenyl)-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDCI3,5): 1.05-1.29 (4H, m), 1.18 (3H, t, J=7Hz), 1.36 (3H, t, J=7Hz), 1.86 (2H, t, J=7Hz), 2.42-2.52 (2H, m), 3.02 (2H, q, J=7Hz), 3.84 (3H, s), 4.02 (2H, q, J=7Hz), 6.02 (1H, d, J=4Hz), 6.60 (1H, d, J=4Hz), 6.95-7.02 (3H, m), 7.36-7.56 (6H,m) Example 170 Ethyl 5-[7-ethyl-2-phenyl-4-(4-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDCI3,6): 1.04-1.29 (4H, m), 1.19 (3H, t, J=7Hz), 1.36 (3H, t, J=7Hz), 1.88 (2H, t, J=7Hz), 2.38-2.48 (2H, m), 3.02 (2H, q, J=7Hz), 4.04 (2H, q, J=7Hz), 5.95 (1H, d, J=4Hz), 6.62 (1H, d, J=4Hz), 7.36 (2H, m), 7.42-7.54 (5H, m), 8.76 (2H, m) Example 171 Ethyl 5-[7-ethyl-2-phenyl-4-(2-pyrazinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDCI3, 5): 1.10-1.32 (4H, m), 1.18 (3H, t, J=7Hz), 1.36 (3H, t, J=7Hz), 1.90 (2H, t, J=7Hz), 2.45-2.55 (2H, m), 3.02 (2H, q, J=7Hz), 4.02 (2H, q, J=7Hz), 6.05 (1H, d, J=4Hz), 6.66 (1H, d, J=4Hz), 7.43-7.56 (5H, m), 8.66 (1H, m), 8.77 (1H, m),8.86(lH,m) Example 172 Ethyl 5-[7-ethyl-2-phenyl-4-(3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDCI3,5): 1.04-1.30 (4H, m), 1.18 (3H51, J=7Hz), 1.37 (3H, t, J=7Hz), 1.87 (2H, t, J=7Hz), 2.38-2.50 (2H, m), 3.02 (2H, q, J=7Hz), 4.01 (2H, q, J=7Hz), 5.96 (1H, d, J=4Hz), 6.63 (1H, d, J=4Hz), 7.42-7.55 (6H, m), 7.77 (1H, m), 8.66-8.73 (2H,m) Example 173 Ethyl 5-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3- yl]pentanoate NMR (CDCI3, 5): 1.12-1.28 (7H, m), 1.36 (3H, t, J=7Hz), 1.89 (2H, t, J=7Hz); 2.43 (2H> m), 3.01 (2H, m), 4.02 (2H, q, J=7Hz), 5.97 (1H, d, J=5Hz), 6.65 (1H, d, J=5Hz), 7.43-7.55 (5H, m), 7.93 (1H, m), 8.61 (1H, m), 8.79 (1H, m) Example 174 Ethyl 5-[4-(5-bromo-3-pyridinyl)-7-ethyl-2 y]]pentanoale NMR (CDCI3, 6): 1.16-1.46 (JOH, m), 1.57 (2H, t, J=7Hz), 2.62 (2H7 m), 2.30 (2H, m), 3.03 (2H,q,J=7Hz),4.05 (2H,q,J=7Hz),5.93 (lH,d,J=5Hz), 6.63 (lH,d, J=5Hz), 7.36 (1H, m), 7.44 (1H, m), 7.91 (1H, m) Example 175 To a solution of ethyl 5-[4-(3-cyanophenyl)-7-ethyl-2-phenylpyrrolo[l ,2-b]pyridazin-3-yl]pentanoate (1.00 g) in dimethylsulfoxide (20 mL) was added IN sodium hydroxide (5.31 mL) over 1.5 hours. The reaction was quenched by adding IN hydrochloric acid (6 mL) under an ice-bath. The mixture was partitioned between ethyl acetate (50 mL) and water (50 mL). The organic layer was washed with water (50 x 2 mL) and brine, dried over magnesium sulfate, and evaporated. Flash silica gel column chromatography eluting with ethyl acetate-hexane = 1/3 to 1/1 afforded 5-[4-(3-cyanophenyl)-7-ethyl-2-phenylpyrro]o[lJ2-b]pyridazin-3-yl]pentanoic acid as an yellow solid (668 mg). 5-[4-(3-Cyanophenyl)-7-ethyL2-phenylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDC13,8): 1.03-1.25 (4H, m), 1.36 (3H, t, J=7Hz), 1.93 (2H, t, J=7Hz), 2.39 (2H, m), 3.02 (2H, q, J=7Hz), 5.91(1H, d, J=5Hz)5 6.63 (1H, d, J=5Hz), 7.26-7.53 (5H, s), 156-1.69 (2H, m), 7.72-7.79 (2H5 m) MS(ESI+):m/z424(M+H) The following compounds were obtained in substantially the same manner as that of Example 175. Example 176 5-[4-(3-Cyanophenyl)-7-ethyl-2-(l,3-lhiazol-2-yl)pyrrolo[l52-b]pyridazin-3-yI]pentanoic acid NMR (CDC13, 5): 1.20-1.52 (7H, m), 2.19 (2H, m), 2.98 (2H, m), 3.04 (2H, q, J=7Hz), 4.05 (2H, q, J=7Hz), 538 (1H, d, J=5Hz), 6.67 (1H, d, J=5Hz), 7.43 (1H, d, J=3Hz), 7.60-7.64 (2H, m), 7.67 (1H, m), 7.76 (1H, m), 7.92 (1H, d, J=3Hz) MS (ESI+): m/z 431 (M+H) Example 177 5-[4-(3-Cyanophenyl)-7-ethyl-2--yl]pentanoic acid NMR (CDC13,5): 1.12 (2H, m), 1.23-1.41 (5H, m), 2.04 (2H,1, J=7Hz), 2.48 (2H, m), 3.02 (2H, q, J=7Hz), 3.68(3H, s), 5.90 (1H, d, J=5Hz), 6.22 (1H, m), 6.35 (1H, m), 6.62 (1H5 d, J=5Hz), 6.75 (1H, m), 7.57-7.789 (4H7 m) MS (ES1+): m/z 427 (M+H) Example 178 5-[4-(3-CyanophenyI)-7-ethyl-2-(l,3-oxazol-5-y])pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3, 5): 1.31-1.49 (7H, m), 2.17 (2H, t, J=7Hz), 2.57 (2H, m), 3.04 (2H, q, J=7Hz), 5.42 (1H, d, J=5Hz), 6.67 (1H, d, J=5Hz), 7.56 (1H, s), 7.64 (2H, m), 7.67 (1H, s), 7.78 (1H, m), 8.07 (1H, s) Example 179 5-[4-(3-Cyanophenyl)-2-(3,5-dimethyl-4-isoxazolyl)-7-ethy]pyrrolo[l,2-b]pyridazin-3-yljpentanoic acid NMR (CDCI3, 8): 1.04-1.30 (7H, m), 1.97 (2H,1, J=7Hz), 2.26-2.35 (5H, m), 2.41 (3H, s), 3.00 (2H, q, J=7Hz), 4.06 (2H, q, J=7Hz), 5.97 (1H, d, J=5Hz), 6,68 (1H, d, J=5Hz), 7.61-7.68 (2H, m), 7.73 (1H, s), 7.79 (1H, m) Example 180 A solution of 3-[(l-amino-5-ethyl-lH-pyrrol-2-y])carbonyl]benzonitrile (120 mg), 1-tert-butyl 7-ethyl 2-[(3,5-dimethyl-4-isoxazolyl)carbonyl1Heptanedioate (203 rng),and toluenesulfonic acid monohydrate (3.76 mg) in toluene (1 mL) was refluxed for 1 hour. Additional p-toluenesulfonic acid monohydrate (14.5 mg) was added, and the mixture was refluxed for 1 hour. The mixture was stirred further for 0.5 hour after adding trifluoromethanesulfonic acid (3.76 mg). The mixture was partitioned between ethyl acetate (20 mL) and saturated sodium bicarbonate (10 mL). The organic layer was washed with brine, dried over magnesium sulfate, and evaporated. Flash silica gel column chromatography eluting with ethyl acetate-bexane = 1/40 to 2/5 afforded ethyl 5-[4-(3-cyanophenyl)-2-(3,5-climethyl-4-isoxazolyl)-7-ethylpyrrolo-[l,2-b]pyridazin-3-yl]pentanoate as an yellow gum (75.7 mg, 19.1%). Ethyl5-[4-(3-cyanophenyl)-2-(3,5-dimethyl-4-isoxazolyl)-7-ethylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDC13,5): 1.04-1.30 (7H, m), 1.97 (2H, t, J=7Hz), 2.26-2.35 (5H, m), 2.41 (3H, s), 3.00 (2H, q, J=7Hz), 4.06 (2H, q, J=7Hz), 5.97 (1H, d, J=5Hz), 6.68 (1H, d, J=5Hz), 7.61-7.68 (2H, m), 7.73 (1H, s), 7.79 (1H, m) Example 181 To a solution of N-[2-(3-cyanobenzoyl)-5-ethyl4H-pyrrol-l-yl]-2-(methylsulfonyl)acetamide (2.70 g) in tetrahydrofuran (30 mL) was added sodium hydride (601 mg, 60% in oil) under an ice-bath. After stirring for 40 minutes, the reaction was quenched by adding IN hydrochloric acid (15 mL). The mixture was extracted with ethyl acetate (50 mL), and the extract was washed with water (50 x 2 mL) and brine (50 mL), dried over magnesium sulfate, and evaporated to give a brownish yellow solid (3.36 g). The solid was triturated in diisopropyl ether (20 mL) to give 3-[7-ethyl-3-(methyIsulfonyl)-2-oxo-l ,2-dihydropyrrolo[l,2-b]pyridazin-4-yl]benzonitrile as an yellow powder (2.31 g, 90.1%). 3-[7-Ethyl-3-(methylsulfonyl)-2-oxo-l,2-dihydropyrrolo[l,2-b]pyridazin-4-yl]benzonitrile NMR (CDCI3, 8): 1.37 (3H, t, J=7Hz), 2.46-3.07 (5H, m), 6.81 (1H, d, J=5Hz), 6.70 (1H, d, J=5Hz), 7.60-7.69 (3H, m), 7.83 (1H, d, J=9Hz) The following compound was obtained in substantially the same manner as that of Example 181. Example 182 Ethyl 4-(4-cyanophenyI)-7-ethyl-2-oxo-l ,2 NMR (CDCI3, 6): 0.78 (3H, t, J=7Hz), 1.36 (3H, t, J=7Hz), 3.02 (2H, q, J=7Hz), 4.02 (2H, q, J=7Hz), 6.15 (1H, d, J=5Hz), 6.64 (1H, d, J=5Hz), 7.42 (2H, d, J=9Hz), 7.77 (2H, d, J=9Hz),11.74 (1H, s, br) MS(ESl+):m/z336(M+H) Example 183 To a solution of 3-[7-ethyl-3-(methylsulfonyl)-2-oxo-l,2-dihydropyrrolo[l,2-b]pyridazin-4-yl]benzonitrile (1.30 g) and triethylarnine (578 mg) in dichloromethane (18 mL) was added trifluoromethanesulfonic anhydride (1.61 g) under an ice-bath over 30 minutes (3 to 7°C). After stirring for 0.5 hour, the reaction was quenched by adding water (100 mL). The mixture was partitioned between ethyl acetate (200 mL) containing chloroform (200 mL) and IN hydrochloric acid (50 mL). An insoluble yellow solid was collected by filtration (0.542 g). The organic layer was washed with brine, dried over magnesium sulfate, and evaporated to give a dark yellow solid (1.27 g). Both the solid was combined, and triturated in diisopropyl ether (30 mL) to give 4-(3-cyanophenyl)-7-ethyl-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazin-2-yl trifluoromethanesulfonate as a brownish yellow powder (1.67 g, 92.6%). 4-(3-Cyanophenyl)-7-ethyl-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazin-2-yl trifluoromethanesulfonate NMR (CDC133 8): 1.39 (3H, t, J=7Hz), 3.02 (2H, q, J=7 Hz,), 3.22 (3H, s), 6.40 (1H, d, J=5Hz), 6.93 (1H, d, J=5Hz), 7.63 (3H, m), 7.82 (1H, m) Example 184 A mixture of 4-(3-cyanophenyl)-7-ethyl-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazin-2-yl trifluoromethanesulfonate (150 mg) and pyrrolidine (45.6 mg) in tetrahydrofuran (1 mL) was refluxed for 1.5 hours. The mixture was partitioned between ethyl acetate (20 mL) and IN hydrochloric acid (10 mL). The organic extract was washed with brine, dried over magnesium sulfate, and evaporated to give a dark colored solid. Flash silica gel column chromatography eluting with ethyl acetate-hexane = 1-4 to 1 -2 afforded 3-[7-ethyl-3-(methylsulfonyl)-2-(l -pyrrolidinyl)- pyrrolo[l,2-b]pyridazin-4-yl]benzonitrile as an yellow oil, which was crystalyzed upon standing (112 mg, 89.6%). 3-[7-Ethyl-3-(rnethylsulfonyl)-2-(l-pyrrolidinyl)pynolo[l,2-b]pyridazin-4-yl]benzonitrile NMR (CDCI3, 8): 1.38 (3H, t, J=7Hz), 1.99 (4H, m), 3.99 (2H, q, J=7Hz), 3.22 (3H, s), 3.42-3.70 (4H, m), 6.28 (1H, d, J=5Hz), 6.68 (1H, d, J=5Hz), 7.57 (1H, t, J=9Hz), 7.69- 7.78 (3H,m) MS (ESI+): m/z 395 (M+H) The following compounds were obtained in substantially the same manner as that of Example 184. Example 185 3-[2-(Dimethylamino)-7-ethyl-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazin-4-yljbenzonitrile NMR (CDC13, 5): 1.39 (3H, t, J=7Hz), 2.97 (6H, s), 3.02 (2H, q, J=7Hz), 3.26 (3H, s), 6.28 (1H, d, J=5Hz), 6.69 (1H, d, J=5Hz), 7.57 (1H, t, J=9Hz), 7.66- 7.79 (3H, m) MS (ES1+): m/z 369 (M+H) Example 186 3-[7-Ethyl-2-[(2-methoxyethyl)amino]-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazin-4- yl]benzonitrile NMR (CDC13,5): 1.35 (3H, t5 J=7Hz), 2.96 (2H, q, J=7Hz), 3.07 (3H, s), 3.43 (3H, s), 3.61-3.73 (4H, m), 5.96 (1H, d, J=5Hz), 6.51 (1H, d, J=5Hz), 6.75 (1H, m, br), 7.51- 7.60 (3H,m), 7.74 (lH,m) MS(ESI+):m/z399(M+H) Example 187 A mixture of ethyl 2-(4-fluorobenzoyl)-3-oxo-4-phenylbutanoate (1.4 g), 1H-pyrrol-1-amine (350 mg), and p-toluenesulfonic acid monohydrate (41 mg) in ethanol (10 ml) was refluxed for 5 hours. The mixture was partioned between ethyl acetate and water. The organic layer was separated, washed with brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of ethyl acetate and hexane (1:4) to give ethyl 2-benzyl-4-(4-iluorophenyl)pyrrolo[l,2-b]pyridazine-3-carboxylate (828 mg) as an oil. Ethyl 2-benzyl-4-(4-fluorophenyl)pyrrolo[l,2-b]pyridazine-3-carboxylate NMR (CDCI3, 5): 0.70 (3H, t, J=7Hz), 3.71 (2H, q, J=7Hz), 4.29 (2H, s), 6.37 (1H, dd, J=l, 4Hz), 6.85 (1H, dd, J=2,4Hz), 7.10-7.30 (7H, m), 7.38-7.46 (2H, m), 7.83(lH,dd,l,2Hz) Example 188 To a solution of ethyl 2-benzyl-4-(4-fluorophenyl)pyrrolo[l,2-b]pyridazine-3-carboxylate (730 mg) in tetrahydrofuran (10 ml) was added N-chlorosuccinimide (260 mg) and the mixture was stirred at 20°C for 2 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with aqueous sodium thiosulfate, water and brine, dried over magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatograpy eluting with a mixture of toluene and ethyl acetate (10:1) to give ethyl 2-benzyl-7-chloro-4-(4-fluorophenyl)pyrrolo[l,2-b]pyridazine-3-carboxylate (285 mg) as an yellow oil. Ethyl 2-benzyl-7-chloro-4-(4-fluorophenyl)pyrrolo[l,2-b]pyridazine-3-carboxylate NMR (CDCI3,5): 0.69 (3H, t, J=7Hz), 3.70 (2H, q, J=7Hz), 437 (2H, s), 6.39 (1H, d, J=4Hz), 6.82 (1H, d, J=4Hz), 7.10-7.30 (7H, m), 7.35-7.45 (2H, m) Example 189 A mixture of ethyl 3-(4-fluorobenzoyl)-4-oxopentanoate (800 mg), lH-pyrrol-1-amine (265 mg), and p-toluenesulfonic acid monohydrate (31 mg) in ethanol (5 ml) was refluxed for 5 hours. The mixture was partioned between ethyl acetate and water. The organic layer was separated, washed with brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of ethyl acetate and hexane (1:4) to give ethyl [4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]acetate (1.09 g) as an oil. Ethyl [4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]acetate NMR (CDCI3, 5): 1.25 (3H, t, J=7Hz), 2.45 (3H, s), 3.45 (2H, s), 4.16 (2H, q, J=7Hz), 6.03 (1H, dd, J=l, 4Hz), 6.72 (1H, dd, J=2, 4Hz), 7.17 (2H, dt, J=2,7Hz), 7.40 (2H, ddd, J =2, 5, 7Hz), 7.68 (1H, dd, J=l, 2Hz) Example 190 To a solution of ethyl [4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridaz)ji-3-yljacetate (100 mg) in tetrahydrofuran (2 nil) was added N-chlorosuccinimide (43 mg) and the mixture was stirred at 20°C for 2 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with aqueous ethyl acetate, water and brine, dried over magnesium sulfate, and evaporated. The residue was purified by silica gel column chromatograpy eluting with a mixture of toluene and ethyl acetate (10:1) to give ethyl [7-chloro-4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]acetate (34 mg) as an yellow oil. Ethyl [7-chloro-4-(4-fluorophenyI)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]acetate NMR (CDCI3,8): 1.25 (3H, t, J=7Hz), 2.54 (3H, s), 3.47 (2H, s), 4.16 (2HS q, J=7Hz), 6.05 (1H, d, J=4Hz), 6.68 (1H, d, J=4Hz), 7.18 (2H, dt, J=2,7Hz), 7.38 Example 191 To a solution of ethyl [7-chloro-4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]acetate (300 mg) in tetrahydrofuran (4 ml) was added IN sodium hydroxide (1.7 ml), followed by methanol (2 ml). After standing at 20°C overnight, the mixture was partitioned between IN hydrochloric acid and ethyl acetate. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was triturated with ether to give [7-chloro-4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]acetic acid (250 mg) as an yellow powder. [7-Chloro-4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]acetic acid NMR (CDCI3,8): 2.57 (3H, s), 3.54 (2H, s), 6.06 (1H, d, J=4Hz), 6.69 (1H, d, J=4Hz), 7.19 (2H, t, J=7Hz), 7.38 (2H, dd, J=5,7Hz) Example 192 To a solution of [7-chloro-4-(4-fluorophenyl)-2-methy]pyrrolo[l,2-b]pyridazin-3-y]]acetic acid (220 mg) in tetrahydrofuran (10 rnl) was added 1,1 -carbonyldiimidazole (18 mg) and the mixture was stirred at 20°C for 1 hour, then magnesium bis(3-ethoxy-3-oxo-propanoate) (109 mg) was added. After the mixture was stirred overnight at 20°C, magnesium bis(3-ethoxy-3-oxo-propanoate) (109 mg) was added. After stirring for 3 hours, the mixture was partitioned between IN hydrochloric acid and ethyl acetate. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of ethyl acetate and hexane (1:5) to give the product (237 mg) as an oil, which was triturated with ethyl acetate and washed with isopropyl ether to give ethyl 4-[7-chloro-4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]-3-oxobutanoate (212 mg) as an yellow powder. Ethyl 4-[7-chloro-4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]-3-oxobutanoate mp 116-118°C NMR (CDC13, 5): 1.25 (3H, t, J=7Hz), 2.46 (3H, s), 3.40 (2H, s), 3.75 (2H, s), 4.16 (2H, q, J=7Hz), 6.04 (1H, d, J=4Hz), 6.68 (1H, d, J=4Hz), 7.20 (2H, t, J=7Hz), 7.28(2H,dd,J=5,7Hz) Example 193 To a solution of ethyl 4-[7-chloro-4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]-3-oxo-butanoate (160 mg) in methanol (5 ml) was added sodium borohydride (23.4 mg) at 0°C and the mixture was stirred at the same temperature for 1 hour. The mixture was partitioned between IN hydrochloric acid and ethyl acetate. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was purified by preparative thin-layer chromatograpy eluting with a mixture of ethyl acetate and hexane (1:3) and triturated with ethyl acetate to give ethyl 4-[7-chloro-4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yI]-3-hydroxybutanoate (95 mg) as an yellow powder. Ethyl 4-[7-chloro-4-(4-fluorophenyl)-2-methylpyrroIo[l,2-b]pyridazin-3-yl]-3- hydroxybutanoate NMR (CDCI3, 5): 1.23 (3H, t, J=7Hz), 2.18-2.38 (2H, m), 2.67 (3H, s), 2.70-2.85 (2H, m), 4.03 (1H, m), 4.09 (2H, q, J=7Hz), 5.96 (1H, d, J=4Hz), 6.65 (1H, d, J=4Hz), 7.19 (2H, t, J=7Hz), 7.30-7.45 (2H, m) Example 194 To a solution of ethyl 4-[7-chloro-4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]-3-hydroxybutanoate (52 mg) in tetrahydrofuran (1 ml) was added IN sodium hydroxide (0.27 ml), followed by methanol (1 ml). After standing at 20°C overnight, the mixture was partitioned between IN hydrochloric acid and ethyl acetate. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated to give 4-[7-chloro-4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]-3-hydroxybutanoic acid (45 mg) as an yellow oil. 4-[7-Chloro-4-(4-fluorophenyl)-2-methylpyrrolo[l32-b]pyridazin-3-yl]-3-hydroxybutanoic acid NMR (CDCI3,8): 2.125-2.45 (2H, m), 2.66 (3H, s), 2.70-2.88 (2H, m), 4.02 (1H, m), 5.97 (1H, d, J=4Hz), 6.65 (1H, d, J=4Hz), 7.20 (2H, t, J=7Hz), 7.30-7.45 (2H, m) Example 195 A mixture of ethyl 7-(4-fluorobenzoyl)-8-oxononanoate (300 mg)7 (l-amino-5-ethyl-lH-pyrrol-2-yl)(4-fluorophenyl)methanone (216 mg), and p-toluenesulfonic acid monohydrate (35.4 mg) in ethanol (6 ml) was refluxed for 5 hours. The mixture was partioned between ethyl acetate and water. The organic layer was separated, washed with brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of ethyl acetate and hexane (1:4) to give ethyl 6-[7-ethyl-2,4-bis(4-fluorophenyl)pyrrolo[l,2-b]pyridazin-3-yl1Hexanoate (83 mg) and ethyl 6-[7-ethyl-4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl1Hexanoate (40 mg) as an oil. Ethyl 6-[7-ethyl-2,4-bis(4-fluorophenyl)pyrrolo[l,2-b]pyridazin-3-yl1Hexanoate NMR (CDC13, 8): 0.85-1.00 (2H, m), 1.00-1.10 (2H, m), 1.16-1.30 (2H, m), 1.21 (3H, t, J=7Hz), 136 (3H, t, J=7Hz), 2.00 (2H, t, J=7Hz), 2.40 (2H, t, J=7Hz), 3.01 (2H, q, J=7Hz), 4.06 (2H, q, J=7Hz), 5.97 (1H, d, J=4Hz), 6.61 (1H, d, J=4Hz), 7.12-7.24 (4H, m), 7.38 (2H, dd, J=5,9Hz), 7.50 (2H, dd, J=5,9Hz) Ethyl 6-[7-ethyl-4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl1Hexanoate NMR (CDC13,5): 1.15-1.30 (2H, m), 1.23 (3H, t, J=7Hz), 1.35-1.45 (2H, m), 1.37 (3H, t, J=7Hz), 1.45-1.55 (2H, m), 2.18 (2H, t, J=7Hz), 2.40 (2H, t, J=7Hz), 2.54 (3H, s), 3.01 (2H, q, J=7Hz), 4.10 (2H, q, J=7Hz), 5.85 (1H, d, J=4Hz), 6.49 (1H, d, J=4Hz), 7.16 (2H, t, J=9Hz), 7.32 (2H, dd, J=5, 9Hz) Example 196 A mixture of (l-amino-5-ethyl-lH-pyrrol-2-yl)(4-fluorophenyl)methanone (500 mg), ethyl 8-acetyl-9-oxodecanoate (678 mg), and p-toluenesulfonic acid monohydrate (82 mg) in ethanol (5 ml) was refluxed for 2 hours. The mixture was partioned between ethyl acetate and IN hydrochloric acid. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with toluene to give ethyl 6-[7-ethyl-4-(4-fluorophenyl)-2-methylpyrrolo[l,2-eb]pyridazin-3-yl1Hexanoate (130 mg) as an oil and [5-ethyl-l-({(lE)-l-[7-ethyl-4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]ethylidene}amino)-lH-pyrrol-2-yl](4-fluorophenyl)-methanone (70 mg) as an yellow crystal. [5-Ethyl-l-({(lE)-l-[7-ethyl-4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]ethylidene}amino)-lH-pyrrol-2-yl](4-fluorophenyl)methanone NMR (CDCI3,5): 1.13 (3H, t, J=7Hz), 1.39 (3H, t, J=7Hz), 1.80-2.00 (2H, m), 1.91 (3H, s), 2.86 (3H, s), 3.06 (2H, q, J=7Hz), 5.97 (1H, d, J=4Hz), 6.11 (1H, d, J=4Hz), 6.62 (2H, t, J=4Hz), 7.11 (4H, t, J=9Hz), 7.48 (2H, dd, J=5, 9Hz) , 7.82 (2H,dd,J=5,9Hz) Ethyl 6-[7-ethyl-4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl1Hexanoate NMR (CDCI3, 5): 1.15-1.30 (2H, m), 1.23 (3H, t, J=7Hz), 1.35-1.45 (2H, m), 1.37 (3H, t, J=7Hz), 1.45-1.55 (2H, m), 2.18 (2H, t, J=7Hz), 2.40 (2H, t, J=7Hz), 2.54 (3H, s), 3.01 (2H, q, J=7Hz), 4.10 (2H, q, J=7Hz), 5.85 (1H, d, J=4Hz), 6.49 (1H, d, J=4Hz), 7.16 (2H, t, J=9Hz), 7.32 (2H, dd, J=5, 9Hz) Example 197 A mixture of ethyl 7-(4-cyanobenzoyl)-8-oxononanoate (2.2 g), 2-elhyl-lH-pyrrol-1-amine (809 mg), and p-toluenesulfonic acid monohydrate (64 mg) in toluene (40 ml) was refluxed for 20 minutes. The mixture was partioned between ethyl acetate and IN hydrochloric acid. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was chromatographed on silica gel eluting with a mixture of ethyl acetate and hexane (1:5) to give the product, which was triturated with hexane to give ethyl 6-[4-(4-cyanophenyl)-7-ethyl-2-methyIpyrrolo-[l,2-b]pyridazin-3-yl1Hexanoate (2.21 g) as an yellow crystals. Ethyl 6-[4-(4-cyanophenyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl1Hexanoate NMR (CDC13,5): 1.15-1.25 (2H,m), 1.25 (3H, t, J=7Hz), 130-1.45 (2H,rn), 1.38 (3H, t, J=7Hz), 1.45-1.65 (2H, m), 2.19 (2H, t, J=7Hz), 2.38 (2H, t, J=7Hz), 2.56 (3H, s), 3.02 (2H, q, J=7Hz), 4r12 (2H, q, J=7Hz), 5.80 (1H, d, J=4Hz), 6.51 (1H, d, J=4Hz), 7.48 (2H, t, J=9Hz), 7.78 (2H, d, J=9Hz) Example 198 To a solution of ethyl 6-[4-(4-cyanophenyl)-7-ethyl-2-methylpyrroIo[l,2-b]pyridazin-3-yl1Hexanoate (1.5 g) in tetrahydrofuran (15 ml) was added 2N potassium hydroxide (7.4 ml), followed by methanol (7.4 ml). After stirring at 50°C for 2 hours and 60°C for 3 hours, the mixture was partitioned between IN hydrochloric acid and ethyl acetate. The precipitates were filtered and washed with ethyl acetate. The organic layer and the washings were combined, washed with water and brine, dried over magnesium sulfate, and evaporated. The residue was triturated with ethyl acetate and the precipitates were filtered. The filtrate was purified by silica gel column chromatograpy eluting with a mixture of ethyl acetate and hexane (1:1) and triturated with isopropyl ether to give 6-[4-(4-cyanophenyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl1Hexanoic acid (650 mg) as an yellow crystals. The two precipitates were combined and recrystallized from ethyl acetate to give 6-{4-[4-(aminocarbonyl)phenyl]-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl}hexanoic acid (550 mg, 37.6%) as an yellow crystals. 6-[4-(4-Cyanopheny])-7-ethyl-2-meihylpyrrolo[l72-b]pyridazin-3-y]1Hexanoicacid NMR(CDC13,§): 1.15-1.30 (2H,m), 1.35-1.45 (2H,m), 1.38 (3H,t,J=7Hz), 1.45- 1.60 (2H, m), 2.26 (2H, t, J=7Hz), 2.38 (2H, t, J=7Hz), 2.56 (3H, s), 3.02 (2H, q, J=7Hz), 5.80 (1H, d, J=4Hz), 6.51 (1H, d, J=4Hz), 7.48 (2H, t, J=9Hz), 7.79 (2H, d,J=9Hz) 6-{4-[4-(Aminocarbonyl)phenyl]-7-ethyl-2-meth-acid NMR (CDC13,8): 1.1-1.20 (2H, m), 1.29 (3H, t, J=7Hz), 130-1.45 (4H, m), 2.10 (2H, t, J=7Hz), 2.37 (2H, t, J=7Hz), 251 (3H, s), 2.92 (2H, q, J=7Hz), 5.73 (1H, d, J=4Hz), 6.51 (1H, d, J=4Hz), 7.45 (2H, t, J=9Hz), 7.47 (1H, s), 7.80 (2H, d, J=9Hz),8.09(lH,s) Example 199 To a solution of 3-[(l-amino-5-ethyl-lH-pyrrol-2-yI)carbonyl]benzonitrile (200 mg) in toluene (6 mL) was added 2,4-pentanedione (837 mg) and p-toluenesulfonic acid monohydrate (32 mg) at ambient temperature. The reaction mixture was refluxed for 1 hour. The residue was purified by flash silica gel chromatography (silica gel, 80 mL) eluted with hexane-ethyl acetate = 10-1 to give 3-(3-acetyl-7-ethyI-2-methyIpyrrolo[l,2-b]pyridazin-4-yl)benzonitriIe (63 mg, 24.8%) as an yellow solid. 3-(3-Acetyl-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-4-yl)benzonitrile NMR (CDCI3,5): 1.39 (3H, t, J=8Hz), 1.95 (3H> s), 2.50 (3H, s), 3.04 (2H, q, J=8Hz), 6.27 (1H, d, J=5Hz), 6.69 (1H, d, J=5Hz), 7.59-7.72 (2H, m), 7.76-7.84 (2H, m) MS (ES1+): m/z 304 (M+H) Example 200 To a solution of ethyl (2E)-3-[7-chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazin-3-yl]-2-propenoate (50 mg) in toluene was added dropwise 15 M diisobutylalminum hydride (0.277 mL) in toluene (24 mL) in a dryice-acetone bath. After addition, the mixture was stirred for 2 hours (-10°C). The reaction mixture was quenched with sodium, potassium-tartarate and was filtered through Celite. The organic layer was separated, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by flash silica gel chromatography (silica gel, 40 mL) eluted with hexane-ethyl acetate = 10-1,5-1, and 3-1 to give (2E)-3-[7-chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazin-3-yl]-2-propen-l-ol as an yellow solid (30 mg). (2E)-3-t7-Chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazin-3-yl]-2-propen-l-ol NMR(CDC13,5): 1.38 (6H,d, J=7Hz), 3.31 (lH,m), 4.05-4.11 (2H,m),5.48 (lH,dt, J=15, 6Hz), 6.11 (1H, d, J=5Hz), 6.45 (1H, d, J=15Hz), 6.68 (1H, d, J=5Hz), 7.08-7.18 (2H, m), 7.29-7.40 (2H, m) MS(ESI"):m/z345(M+H) The following compounds were obtained in substantially the same manner as that of Example 200. Example 201 [4-(4-Fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]methanol NMR (CDC13,5): 1.45 (1H, t, J=5Hz), 2.65 (3H, s), 4.47 (2H, d, J=5Hz), 6.13 (1H, m), 6.73 (1H, m), 7.14-7.28 (2H, m), 7.43-7.51 (2H, m), 7.70 (1H, m) MS (ESI+): m/z 257 (M+H) Example 202 [7-Ethyl-4-(4-fluorophenyl)-2-isopropylpyrrolo[lJ2-b]pyridazin-3-yl]methanol NMR (CDCI3,5): 1.31-1.46 (10 H, m), 3.04 (2H, q, J=8Hz), 346 (1H, m), 4.49 (2H, d, J=5Hz), 6.05 (1H, d, J=5Hz), 6.56 (1H, d, J=5Hz), 7.12-7.22 (2H, m), 7.41-7.50 (2H, m) MS(ESI+):m/z313(M+H) Example 203 2-{[7-Ethyl-4-(4-fluorophenyl)-2-isopropylpyrrolo[l52»b]pyridazin-3-yl]methoxy}ethanol NMR (CDCJ3, 8): 1.30-145 (9 H, m), 3.04 (2H, q, J=8Hz), 3.35 (1H, m), 3.46 (2H, t, J=6Hz), 3.69 (2H, br t, J=8Hz), 4.30 (2H, s), 6.07 (1H, d, J=5Hz), 6.55 (1H, d, J=5Hz), 7.11-7.22 (2H, m), 7.41-7.51 (2H5 m) MS(ESl+):m/z357(M+H) Example 204 To a solution of (2E)-3-[7-chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazin-3-yl]-2-propen-l-ol (30 mg) in N,N-dimethylformamide (1 mL) was added 60% sodium hydride in oil (3.8 mg) in an ice-water bath under nitrogen atmosphere. After 20 minutes, to the mixture was added methyl iodide (18.5 mg) at the temperature. After 15 minutes, the reaction mixture was stirred at ambient temperature for 5 hours. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water three times and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by p-TLC (hexane-ethyl acetate = 10-1) to give 7-chloro-4-(4-fluorophenyl)-2-isopropyl-3-[(lE)-3-methoxy-l-propenyl]pyrrolo[l,2-b]pyridazine as a brown oil (3.5 mg, 10.2 %). 7-Chloro-4-(4-fluorophenyl)-2-isopropyl-3-[(lE)-3-methoxy-l-propenyl]pyrrolo[l,2-b]pyridazine NMR (CDC13, 8): 1.38 (3H, t, J=7Hz), 3.31 (1H, m), 4.05-4.11 (2H, m), 5.48 (1H, dt, J=15, 6Hz), 6.11 (1H, d, J=5Hz), 6.45 (1H, d, J=15Hz), 6.68 (1H, d, J=5Hz), 7.08-7.18 (2H, m), 7.29-7.40 (2H, m) MS(ESr):m/z345(M+H) Example 205 To dimethylsulfoxide (0.5 mL) was added 60% sodium hydride in oil (27 mg) and was heated at 60°C for 40 minutes. To this mixture was added (3-carboxypropyl)(triphenyl)phosphonium bromide (124 mg) at ambient temperature and was stirred for 40 minutes. 7-Chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazine-3-carbaldehyde (40 mg) was added therein at ambient temperature. After 4 hours, the reaction mixture was acidified with IN hydrogen chloride and was partitioned between ethyl acetate and water. The organic layer was washed with water three times and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by p-TLC (hexane-ethyl acetate = 1-1) to give (4E)-5-[7-chloro-4-(4- fluorophenyl)»2-isopropylpyrro]o[l,2-b]pyridazin-3-yl]-4-pentenoic acid as an yellow oil (21mg,E:Z=16:l,563%). (4E)-5-[7-Chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l32-b]pyridazin-3-yl]-4-pentenoic acid NMR (CDCI3, 5): 1.40 (6H, d, J=7Hz), 2.20-2.37 (4H, m), 3.25 (1H, m), 5.30 (0.94H, dt, J=15,7Hz), 5.01 (0.06H, m), 6.09 (1H, d, J=5Hz), 6.24 (0.94H, d, J=15Hz), 6.84 (0.06H, d, J=10Hz), 6.67 (0.94H, d, J=5Hz), 6.70 (0.06H, d, J=5Hz), 7.07-7.17 (2H, m), 7.26-7.35 (2H, m). MS (ESI'): m/z 385 (M-H) Example 206 To a solution of 7-chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazine-3-carbaldehyde (40 mg) was added IN sodium hydroxide (193 mg) and acetone (0.425 mL) at ambient temperature. After 8 hours, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by p-TLC (hexane-ethyl acetate = 5-1) to give (3E)-4-[7-chloro-4-(4-fluorophenyl)-2-isopropylpyrroIo[l,2-b]-pyridazin-3-yl]3-buten-2-one as an yellow solid (33 mg). (3E)-4-[7-Chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazin-3-yl]-3-buten-2-one NMR (CDCI3, 5): 1.40 (6H, d, J=7Hz), 2.13 (3H, s), 3.38 (1H, m), 5.89(1H, d, J=15Hz), 6.23 (1H, d, J=5Hz), 6.75 (1H, d, J=5Hz), 7.13-7.23 (2H, m), 7.30-739 (2H,m),7.49(lH,d,J=15Hz) Example 207 A solution of ethyl 4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazine-3-carboxylate (100 mg) in tetrahydrofuran (1 mL) was purged with nitrogen gas under a dryice-acetone bath. To the mixture was added 2,2-azobisisobutyronitrile (0.5 mg) was added to the mixture. After 5 minutes, was added l,3-dibromo-5,5-dimethy]-2,4-imidazolidinedione (43.8 mg). The resulting mixture was stirred for 3 hours (-78 to - 30°C). Water (5 mL) was added, and the mixture was extracted with ethyl acetate. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, and evaporated to give an yellow gum. Flash silica gel column chromatography eluting with toluene-hexane = 1-5 to 2-3 afforded ethyl 7-bromo-4-(4-fIuorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazine-3-carboxylate product as an yellow gum (90.0 mg, 72.5%). Ethyl 7-bromo-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazine-3-carboxylate NMR (CDC13,8): 0.98 (3H, t, J=7Hz), 1.40 (6H, d, J=7Hz), 3.31 (1H, septet, J=7Hz), 4.05 (2H, q, J=7Hz), 639 (1H, d, J=5Hz), 6.87 (1H, d, J=5Hz), 7.16 (2H, t, J=9Hz), 7.45 (2H, dd, J=4 and 9Hz) MS(ESI+):m/z405(M+H) Example 208 A suspension of sodium hydride (74.4 mg) in dimethylsulfoxide (1.4 mL) was stirred for 1 hour at 60°C. The mixture was added to a solution of methyl triphenylphosphonium bromide (1.11 g) in dimethylsulfoxide (1.0 mL) at room temperature. After stirring for 0.5 hour, the mixture was added ethyl 4-(4-fluorophenyl)-7-formyl-2-isopropylpyrrolo[l,2-b]pyridazine-3-carboxy]ate (500 mg). After stirring for 15 hours, the mixture was partitioned between ethyl acetate (20 mL) and water (5 mL). The organic layer was washed with water and brine, dried over anhydrous magnesium sulfate, and evaporated to give an orange gum. Flash silica gel column chromatography eluting with ethyl acetate-hexane = 1-7 to 3-1 afforded ethyl 4-(4-fluorophenyl)-2-isopropy]-7-vinylpyrrolo[l,2-b]pyridazine-3-carboxylate an yellow gum, which was solidified upon standing (361 mg, 72.6%). Ethyl 4-(4-fluorophenyl)-2-isopropyl-7-vinylpyrrolo[l,2-b]pyridazine-3-carboxylate NMR (CDCI3, 8): 0.97 (3H, t, J=7Hz), 1.38 (6H, d, J=7Hz), 3.32 (1H, septet, J=7Hz), 4.03 (2H, q, J=7Hz), 5.35 (1H, dd, J=2 and 12Hz), 6.11 (1H, dd, J=2 and 18Hz), 6.34 (1H, d, J=5Hz), 6.99 (1H, d, J=5Hz), 7.16 (1H, t, J=9Hz), 7.25 (1H, dd, J=12 and 18Hz), 7.45 (2H, d, J=4 and 9Hz) Example 209 To a solution of ethyl 7-{4-[4-({[(benzyloxy)carbonyl]-amino}sulfonyl)phenyl]-7-ethyl-2-methylpyrrolo[l,2--b]pyridazin-3-yl}heptanoate (169 mg) in ethanol (2 xnL) was added 10% palladium on activated carbon (1.6 mg), and the mixture was stirred under hydrogen pressure (3 kg/cm2) for 2 hours. The resulting mixture was filtered through celite, and the filtrate was concentrated to give an yellow gum. Preparative silica gel thin layer chromatography eluting with ethyl acetate-hexane = 1-1 afforded ethyl 7-{4-[4-(aminosulfonyl)phenyl]-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl}heptanoate as an yellow gum (76.8 mg, 58.4%). Ethyl 7-{4»[4-(aminosulfonyl)phenyl]-7-ethyl-2-methylpyrrolo[l52-b]pyridazin-3-yl}heptanoate NMR (CDC13, 5): 1.07-1.25 (7H, m), 1.30-1.46 (7H, m), 2.18 (2H, t, J=7Hz), 2.36 (2H, m), 2.55 (3H, s), 3.00 (2H, q, J=7Hz), 4.12 (2H, q, J=7Hz), 5.21 (2H, s), 5.82 (1H, d, J=5Hz), 6.50 (1H, d, J=5Hz), 7.52 (2H, d, J=9Hz), 8.05 (2H, d, J=9Hz) MS (ESI+): m/z 472 (M+H) Example 210 To a solution of ethyl 4-(4-cyanophenyl)-2-(2-ethoxy-2-oxoethyl)-7-ethylpyrrolo[l,2-b]pyridazine-3-carboxylate (77.9 mg) in ethanol (0.5 mL)-tetrahydrofuran (0.5 mL) was added IN potassium hydroxide. The resulting solution was stirred for 2.5 hours at room temperature. The mixture was stirred for futher 1 hour after adding IN potassium hydroxide (0.04 mL). The reaction was quenched by adding IN hydrochloric acid (0.23 mL). The volatile was evaporated off, and the resulting residue was partitioned between ethyl acetate (10 mL) and IN hydrochloric acid (6 mL). The organic layer was washed with brine, dried, and evaporated to give [4-(4-cyanophenyl)-3-(ethoxycarbonyl)-7-ethylpyrrolo[l,2-b]pyridazin-2-yl]acetic acid as an yellow solid (67.7 mg,93.4%). [4_(4-Cyanophenyl)-3-(ethoxycarbonyl)-7-ethylpyrrolo[l,2-b]pyridazin-2-yl]acetic acid NMR (CDC13,5): 0.84 (3H, t, J=7Hz), 1.38 (3H, t, J=7Hz), 3.05 (2H, q, J=7Hz), 3.93 (2H, q, J=7Hz), 4.18 (3H, s), 6.27 (1H, d, J=5Hz), 6.74 (1H, d, J=5Hz), 7.52 (2H, d, J=9Hz), 7.76 (2H, d, J=9Hz) MS(ESl+):m/z378(M-fH) Example 211 To a solution of ethyl 2-(2-amino-2-oxoethyl)-4-(4-cyanophenyl)-7-ethylpyrrolo[l,2-b]pyridazine-3-carboxylate (35.0 mg) in tetrahydrofuran (1 mL) was added 60% sodium hydride (4.50 mg) under an ice-bath. The resulting mixture was stirred for 1 hour. The reaction was quenched by adding IN HC1 (4 mL). The mixture was extracted with ethyl acetate (10 mL), and the organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated. Preparative silica gel thin layer chromatography eluting with ethyl chloroform-methanol = 10-1 afforded 4-(7-ethyl-l33-dioxo-l-jS--tetrahydropyridolS--ejpyrrolotl--b]-pyridazin-10-yl)benzonitrile as an yellow solid (3.86 mg, 12.6%). 4-(7-ethyl-13-dioxo-l,253,4-tetrahydropyrido[3,4-e]pyrrolo[l,2-b]pyridazin-10-yl)benzonitrile NMR (CDC13,5): 1.40 (3H, t, J=7Hz), 3,08 (2H, q, J=7Hz), 4.16 (3H, s), 6.38 (1H, d, J=5Hz), 6.85 (1H, d, J=5Hz), 7.46 (2H, d, J=9Hz), 7.78 (2H, d, J=9Hz), 7.92 (1H, s,br) Example 212 To methanol (1 mL) was added 60% sodium hydride (6.51 mg) at room temperature. Then,4-(3-cyanophenyl)-7-ethyl-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazin-2-yl trifluoromethanesulfonate (70.0 mg) was added to the mixture. The resulting mixture was stirred for 2 hours at room temperature and 1 hour at 50°C. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over magnesium sulfate, and evaporated. Preparative silica gel thin layer chromatography eluting with ethyl acetate-hexane = 1-1 afforded 3-[7-ethyl-2-methoxy-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazin-4-yl]benzonitrile as an yellow solid (1.92 mg, 3.7%). 3-[7-Ethyl-2-methoxy-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazin-4-yl]ben2onitrile NMR (CDCI3,5): 1.38 (3H, t, J=7Hz), 3.01 (2H, q, J=7Hz,), 3.24 (3H, s), 4.18 (3H, s), 6.12 (1H, d, J=5Hz), 6.63 (1H, d, J=5Hz), 7.53-7.64 (3H, m), 7.76 (1H, m) Example 213 To a solution of ethyl 4-(3-cyanophenyl)-7-ethyl-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazine-2-carboxylate (92.6 mg) in telrahydrofuran (1 mL) and ethanol (0.5 mL) was added IN sodium hydroxide (0.349 mL). The resulting mixture was stirred for 3 hours at room temperature. The resulting mixture was stirred further for 40 minutes after adding IN sodium hydroxide (0.1 mL). The mixture was stirred further for 1.5 hours after adding IN sodium hydroxide (0.1 mL). The reaction was quenched by adiding IN hydrochloric acid (1 mL), and the mixture was partitioned between ethyl acetate (20 mL) and water (10 mL). The organic layer was washed with brine, dried over magnesium sulfate, and evaporated to give a red oil. Flash silica gel column chromatography eluting with ethyl acetate-hexane = 1-1 afforded 3-(6-ethyl-l,l-dioxido-3-oxo-2,3-dihydropyrrolo[l,2-b]thieno[2,3-e]- pyridazin-9-yl)benzonitrile as a red foam (52.4 mg, 64.0%). 3-(6-Ethyl-l,l-dioxido-3-oxo-253-dihydropyrrolo[l,2-b]thieno[2,3-e]pyridazin-9-yl)benzonitrile NMR (CDC13,5): 1.45 (3H, t, J=7Hz), 3.21, (3H, s), 4.28 (2H, s), 6.91 (1H, d, J=5Hz), 7.26 (1H, d, J=5Hz), 7.75 (1H, t, J=9Hz), 7.91 (1H, d, J=9Hz), 8.08-8.16 (2H, m) MS(ESI+):m/z352(M+H) Example 214 To a solution of 3-(6-ethyl-l,l-dioxido-3-oxo-2,3-dihydropyrrolo[l,2-b]thieno[2,3-e]pyridazin-9-yl)benzonitriIe (60.0 mg) in tetrahydrofuran (0.2 mL) was added 1 M solution of borane-tetrahydrofuran complex in tetrahydrofuran (0.487 mL) under an ice-bath. After stirring for 1 hour, the reaction was quenched by adding IN hydrochloric acid (1 mL). The mixture was partitioned between ethyl acetate (20 mL) and water (10 mL), and the organic layer was washed with brine, dried, and evaporated to give 3-(6-ethyl-3-hydroxy-l,l-dioxido-2,3-dihydropyrrolo[l,2-b]thieno[2,3-e]pyridazin- 9-yl)- benzonitrile as an yellow foam (576 mg, 99.8%). 3-(6-Ethyl-3-hydroxy4,l-dioxido-2,3-dihydropyrrolo[l,2-b]thieno[23-e]pyridazin-9-yl)benzonitrile NMR (CDCI3, 5): 1.45 (3H, I, J=7Hz), 3.21, (3H, s), 4.28 (2H, s), 6.91 (1H, d, J=5Hz), 7.26 (1H, d, J=5Hz), 7.75 (IH, t, J=9Hz), 7.91 (1H, d, J=9Hz), 8.08-8.16 (2H, m) Example 215 To a solution of 3-(6-ethyl-3-hydroxy-l ,l-dioxido-2,3-dihydropyrrolo[l,2-b]thieno[2,3-e]pyridazin-9-yl)benzonitrile (54.0 mg) in tetrahydrofuran (1 mL) was added 60% sodium hydride (6.69 mg) under an ice-bath. After stirring for 0.5 hour, methyl iodide (25.9 mg) was added, and the mixture was stirred for 3 hours 20 minutes at room temperature. The mixture was stirred for another 6 hours after adding mehtyl iodide (25.9 mg). The mixture was further stirred for 1 hour after adding 60% sodium hydride (3.0 mg) and methyl iodide (25.9 mg). The mixture was partitioned between ethyl acetate and IN hydrochloric acid, and the organic layer was washed with brine, dried over magnesium sulfate, and evaporated to give an yellow oil. Preparative silica gel thin layer chromatography eluting with ethyl acetate-hexane = 1-2 afforded 3-(6-ethyl-l,l-dioxidopyrrolo[l,2-b]thieno[2,3-e]pyridazin-9-yl)benzonitrile (5.9 mg, 10.5%, an yellow solid) and3-(6-ethyl-3-methoxy-l,l-dioxido-2,3-dihydropyrrolo[l,2-b]thieno[2,3-e]pyridazin-9-yl)benzonitrile (16.8 mg, 30.0%, an orange gum). 3-(6-Ethyl-l,l-dioxidopyiTolo[lJ2-b]thieno[2,3-e]pyridazin-9-yl)benzonitrile NMR (CDC13,5): 1.40 (3H, t, J=7Hz), 3.07 (2H, q, J=7Hz), 6.68 (IH, d, J=5Hz), 6.82 (IH, d, J=5Hz), 7.02 (IH, d, J=7Hz), 7.37 (IH, d, J=7Hz), 7.72 (IH, t, J=9Hz), 7.87 (IH, d, J=9Hz), 8.11-8.16 (2H, m) 3-(6-Ethyl-3-methoxy-l,l-dioxido-2,3-dihydropyrrolo[l,2-b]thieno[2,3-e]pyridazin-9- yl)benzonitrile NMR (CDCI3,6): 1.42 (3H, t, J=7Hz), 3.12 (2H, q, J=7Hz), 3.67 (3H, s), 3.73 (2H, m), 5.02 (IH, m), 6.74 (IH, d, J=5Hz), 6.97 (IH, d, J=5Hz), 7.70 (IH, t, J=9Hz), 7.85 (IH, d, J=9Hz), 8.04-8.13 (2H, m) MS(ESI+):m/z368(M+H) Example 216 A mixture of 3-[(l-amino-5-ethyl-lH-pyrrol-2-yl)carbonyl]benzonitrile (1.00 g), ethyl 3-(methylsulfonyl)-2-oxopropanoate (1.34 g), and p-toluenesulfonic acid monohydrate (79.5 mg) in toluene (20 mL) was refluxed for 1 hour with Dean-Stark condenser, The volatile was removed in vacuo. Flash silica gel column chromatography eluting with ethyl acetate-hexane = 1-10 to 9-15 afforded the intermediate imine (1.38 g, 67.7%) as an orange foam. The foam was dissolved in N-methylmorpholine (10 mL), and the solution was stirred for 1 hour at 130°C. The mixture was partitioned between ethyl acetate (50 mL) and water (30 mL). The organic layer was washed with water (30 x 2 mL) and brine, dried over magnesium sulfate, and evaporated to give a dark orange solid. The solid was triturated in diisopropyl ether (10 mL) to give 2-(trimethylsilyl)ethyl 4-(3-cyanophenyl)-7-ethyl-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazine-2-carboxylate as an yellow powder (1.11 g, 67.7%). 2-(Trimethylsilyl)ethyl4-(3-cyanophenyl)-7-ethyl-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazine-2-carboxylate NMR (CDC13,8): 0.12 (9H, s), 1.22 (2H5 m), 1.39 (3H, t, J=7Hz), 3.09 (2H, q, J=7Hz), 3.23 (3H, s), 4.53 (2H, m), 6.30 (1H, d, J=5Hz), 6.89 (1H, d, J=5Hz), 7.50-7.67 (3H, m), 7.82 (1H, m) MS (ES1+): m/z 470 (M+H) The following compound was obtained in substantially the same manner as that of Example 216. Example 217 Ethyl 4-(3-cyanophenyl)-7-ethyl-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazine-2-carboxylate NMR (CDCI3,8): 1.39 (3H, t, J=7Hz), 1.47 (3H, t, J=7Hz), 3.10 (2H, q, J=7Hz), 3.21, (3H, s), 4.51 (2H, q, J=7Hz), 6.30 (1H, d, J=5Hz), 6.90 (1H, d, J=5Hz), 7.61-7.67 (3H,m),7.72(lH,m) Example 218 A solution of 2-(trimethylsilyI)ethyl 4-(3-cyanophenyl)-7-ethyl-3- (methyIsuIfonyI)pyrrolo[l,2-b]pyridazine-2-carboxylate (1.09 ) in trifluoroacetic acid (5 mL) was stirred for 1.5 hours under an ice-bath. The reaction was quenched by adding water (20 mL). An yellow crystal was formed upon the addition, which was collected by filtration. The crystal was washed with water (5 mL) and hexane (3 mL) to give 4-(3-cyanophenyl)-7-ethyl-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazine-2-carboxylic acid as an yellow crystal (756 mg, 88.2%). 4-(3-Cyanophenyl)-7-ethyl-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazine-2-carboxylicacid NMR (CDC13,5): 1.41 (2H, m), 3.10 (2H, q, J=7Hz), 3.30 (3H, s), 6.36 (1H, d, J=5Hz), 6.94 (1H, d, J=5Hz), 7.53-7.67 (3H, m), 7.82 (1H, m) MS (ESI+): m/z 370 (M+H) Example 219 A mixture of 4-(3-cyanophenyl)-7-ethyl-3-(methylsulfonyI)pyrrolo[l ,2-b]pyridazine-2-carboxylic acid (40.0 mg), diemthylamine hydrochloride (12.4 mg), l-(3-dimethylaminopropyl)-3-ethylcarbodiimide (25.2 mg), and 1-hydroxybenzotriazole (21.9 mg) in N,N-dimethylformamide (1 mL) was stirred for 3 hours at room temperature. The mixture was partitioned between ehtyl acetate (20 mL) and IN hydrochloric acid (10 mL). The organic layer was washed with water (10 x 3 mL), saturated sodium bicarbonate(10 mL), and brine, dried over magnesium sulfate, and evaporated to give 4-(3-cyanophenyl)-7-ethyl-N,N-dimethyl-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazine-2-carboxamide as an yellow solid (43.4 mg, 101%). 4-(3-Cyanophenyl)-7-ethyl-N,N-dimethy]-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazine-2-carboxamide NMR (CDCI3,5): 1.38 (2H, m), 3.07 (2H, q, J=7Hz), 3.12 (3H, s), 3.18 (3H, s), 3.27 (3H, s), 6.27 (1H, d, J=5Hz), 6.85 (1H, d, J=5Hz), 7.57-7.67 (3H, m), 7.81 (1H, m) MS(ESI+):m/z397(M+H) Example 220 A mixture of ethyl 4-(3-chlorophenyl)-7-ethyl-2-(2-furyl)pyrroIo[l ,2-b]pyridazine-3-carboxylate (450 mg) and 85% potassium hydroxide (3.01 g) in a mixture of ethanol (3 mL) and water (2 mL) was refluxed for 2.5 hours. The reaction mixture was cooled under an ice-bath, and quenched by adding concentrated hydrochloric (5 mL). The mixture was partitioned between ethyl acetate (20 mL) and water (10 mL), and the organic layer was washed with brine, dried over magnesium sulfate, and evaporated to give an yellow solid (388 mg). The solid was triturated in hexane to give 4-(3-chlorophenyl)-7-ethyl-2-(2-furyl)pyrrolo[l,2-b]pyridazine-3-carboxylic acid as an yellow powder (361 mg, 86.4%). 4-(3-Chlorophenyl)-7-ethyl-2-(2-furyl)pyrrolo[l,2-b]pyridazine-3-carboxylicacid NMR (CDC13, 5): 1.41 (3H, l, J=7Hz), 3.08 (2H3 q, J=7Hz), 6.37 (1H, d, J=5Hz), 6.55 (1H, m), 6.76 (1H, d, J=5Hz), 7.02 (1H, d, J=3Hz), 7.40-7.55 (5H, m) MS(ESI+):m/z367(M+H) Example 221 To a solution of 4-(3-chlorophenyl)-7-ethyl-2-(2-furyl)pyrrolo[l,2-b]pyridazine-3-carboxylic acid (358 mg,) and N,N-dimethylformamide (1.39 mg) in dichloromethane (3 mL) was added oxalyl chloride (157 mg) at room temperature. After stirring for 30 minutes, the volatile was removed in vacuo, and the residue was azeotroped with toluene three times to afford 4-(3-chlorophenyl)-7-ethyl-2-(2-furyl)pyrrolo[l,2-b]pyridazine-3-carbonyl chloride as an yellow gum (396 mg, 106%). 4-(3-Chlorophenyl)-7-ethyl-2-(2-furyl)pyrrolo[l,2-b]pyridazine-3-carbonyl chloride NMR (CDCI3,5): 1.42 (3H, t, J=7Hz), 3.10 (2H, q, J=7Hz), 6.45 (1H, d, J=5Hz), 6.59 (1H, m), 6.82 (1H, d, J=5Hz), 7.06 (1H, d, J=7Hz), 7.38-7.55 (4H, m), 7.63 (lH,m) Example 222 To a solution of methyl aminoacetate hydrochloride (26.1 mg) and triethylamine (42.0 mg) in dichloromethane (0.5 mL) was added a solution of 4-(3-chlorophenyl)-7-ethyl-2-(2-furyl)pyrrolo[l,2-b]pyridazine-3-carbonyl chloride (40.0 mg) in dichloromethane (0.5 mL) under an ice-bath. The mixture was partitioned between ethyl acetate (20 mL) and IN hydrochloric acid (10 mL), and the organic layer was washed with brine (10 mL), dried over magnesium sulfate, and evaporated to give methyl ({[4-(3- chlorophenyl)-7-ethyl-2-(3-furyl)pyrrolo[l,2-b]pyridazin-3-yl]carbony]}am]no)acetale as an yellow gum (50.6 mg, 111%). Methyl ({[4-(3-chlorophenyl)-7-elhyl-2-(3-furyl)pyrrolo[l,2-b]pyridazin-3-yl]carbonyl}amino)acetate NMR (CDCI3,8): 1.41 (3H, t, J=7Hz), 3.10 (2H, q, J=7Hz), 3.69 (3H, s), 3.95 (2H, d, J=5Hz), 6.01 (1H, t, br, 5Hz), 6.35 (1H, d, J=5Hz), 6.51 (1H, m), 6.75 (1H, d, J=5Hz), 7.01 (1H, d, J=7Hz), 7.37-7.48 (3H, m), 7.53 (1H, m), 758 (1H, m) MS(ESI+):m/z438(M+H) The following compound was obtained in substantially the same manner as that of Example 222. Example 223 4-(3-Chlorophenyl)-7-ethyl-2»(2-furyl)-N,N-bis(2-hydroxyethyl)pyrrolo[l,2-b]pyridazine-3-carboxamide NMR (CDCI3,6): 1.42 (3H, t, J=7Hz), 2.35-2.72 (4H, m), 3.08 (2H, d, J=5Hz), 3.20- 3.63 (4H, m), 3.82 (2H, m), 6.40 (1H, t, br, 5Hz), 6.54 (1H, m), 6.75 (1H, d, J=5Hz), 7.04 (1H, d, J=3Hz), 7.40-7.48 (2H, m), 7.53-7.60 (2H, m), 7.71 (1H, m) MS(ES1+):m/z454(M+H) Example 224 To a solution of 3-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]propanoic acid (100 mg) in dioxane (0.5 mL) was added triethylamine (25.2 mg) followed by a solution of pivaloyl chloride (30.1 mg) in dioxane (0.5 mL). A white precipitate was formed. After stirring for 40 minutes at room temperature, the precipitate was removed by filtration, and washed with dioxane (2 mL). To the combined washing was added a solution of 2-aminoethanesulfonic acid (38.6 mg) in IN sodium hydroxide (0.247 mL). The resulting mixture was stirred for 1 hour at room temperature. The mixture was partitioned between ethyl acetate (15 mL) and water (5 mL). The organic layer was washed with brine, dried over magnesium sulfate, and evaporated. Preparative silica gel thin layer chromatography eluting with chloroform-melhanol = 5-1 afforded 2-({3-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo-[l,2-b]pyridazin-3-yl]propanoyl}amino)ethanesulfonic acid as an yellow solid (104 mg, 82.0%). 2-({3-[4-(3-Chloropheny])-7-elhy]-2-pheny]pyrrolo[l,2-b]pyridazin-3-y]]propanoyl}amino)ethanesulfonic acid NMR (CDC13,5): 1.27 (5H, m), 2.59 (4H, m), 2.90-3.14 (4H, m), 5.96 (1H, m), 6.06 (1H, in), 7.06-7.40 (9H,m) Example 225 A solution of 3-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l ,2-b]pyridazin-3-yl]propanoic acid (100 mg), (2R53R,4S-S,6R)-2-amino-3--bis[(2,2-dimethylpropanoyl)- oxy]-6-{[(232-dimethylpropanoyl)oxy]methyl}tetrahydro-2H-pyran-4-ylpivalate (255 mg), l-(3-dimethylaminopropyl)-3-ethylcarbodiimide (0.494 mmol), and 1-hydroxybenzotriazole (66.7 mg) in N,N-dimethylformamide (1 mL) was stirred for 1 hour at room temperature. The mixture was partitioned between ethyl acetate (20 mL) and IN hydrochloric acid (10 mL). The organic layer was washed with water (10 x 3 mL), saturated Sodium bicarbonate (10 mL), and brine, dried over magnesium sulfate, and evaporated to give an yellow foam (339 mg). Flash silica gel column chromatography eluting with ethyl acetate-hexane = 1-10 to 2-5 afforded (2R,3R,4S-S,6R)-2-({3-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]propanoyl}amino)-3,5-bis[(2,2-dimethylpropanoyl)oxy]-6-{[(2,2-dimethylpropanoyl)-oxy]methy]}tetrahydro-2H-pyran-4-yl pivalate an yellow foam (240 mg, 108%). (2R,3R,4S,5S,6R)-2-({3-[4-(3-Chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]propanoyl}amino)-3,5-bis[(2,2-dimethy]propanoyl)oxy]-6-{[(2,2-dimethylpropanoyl)oxy]methyl}tetrahydro-2H-pyran-4-yl pivalate NMR (CDC13, 8): 0.97-1.26 (36H, m), 1.35 (3H, t, J=7Hz), 1.83 (2H, m), 2.81 (2H, m), 3.01 (2H, q, J=7Hz), 3.87-4.16 (3H, m), 4.90-5.27 (3H, m), 5.36-5.51 (2H, m), 6.01 (1H, d, J=5Hz), 6.52 (1H, d, J=5Hz), 7.29 (1H, m), 7.40-7.59 (8H, m) Example 226 To a solution of ethyl [4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]acetate (114 mg) in tetrahydrofuran (2 mL) was added 1 M diisobutylaluminum hydride in toluene (0.816 mL) under an ice-bath. After stirring for 1 hour at room temperature, additional 1 M diisobutylaluminum hydride (0.41 mL) was added. The reaction was quenched by adding IN hydrochloric acid (1 mL) after 1 hour. The mixture was partitioned between ethyl acetate (20 mL) and IN hydrochloric acid (10 mL), and filtered through celite. The organic layer was washed with water (10 mL) and brine, dried over magnesium sulfate, and evaporated to give an yellow gum. Flash silica gel column chromatography eluting with ethyl acetate-hexane = 1-20 to 2-50 afforded 2-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]ethanol as an yellow oil, which was crystalyzed upon standing (107 mg, 104%). 2-[4-(3-Chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]ethanol NMR (CDC13,5): 1.37 (3H, t, J=7Hz), 2.77 (2H, t, J=7Hz), 3.01 (2H, q, J=7Hz), 3.26 (2H, m), 3.26 (2H, m), 6.00 (1H, d, J=5Hz), 6.63 (1H, d, J=5Hz), 7.34 (1H, m), 7.41-7.55 (8H,m) Example 227 To a mixture of 2-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l;2-b]pyridazin-3-yl]ethanoI (105 mg), 2,3,4,6-tetra-O-acetyl-beta-D-galactosyl bromide (299 mg), silver carbonate (154 mg) in toluene (2 mL) was added silver triflate (3.58 mg) under an ice bath. After 40 minutes, 2,3,4,6-tetra-O-acetyl-beta-D-galactosyl bromide (114 mg), silver carbonate (229 mg) was added, and the mixture was stirred for 50 minutes. The mixtrure was further stirred for 50 minutes after adding 2,3,4,6-tetra-O-acetyl-beta-D-galactosyl bromide (114 mg), silver carbonate (154 mg). The mixture was filtered through celite, and the filtrate was paritiotned between ethyl acetate and water. The organic layer was washed with brine, dried over magnesium sulfate, and evaporated to give an yellow gum. Hash silica gel column chromatography eluting with ethyl acetate-hexane = 1-10 to 7/10 afforded (2R,3R,4S-S,6R)-4,5-bis(acetyloxy)-6-[(acetyloxy)methyl]-2-{2-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]ethoxy}tetrahydro-2H-pyran-3-yl acetate as an yellow gum (115 mg, 58.4%). (2R,3R,4S,5S,6R)-4,5-bis(Acetyloxy)-6-[(acetyloxy)methyl]-2-{2-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]ethoxy}tetrahydro-2H-pyran-3-yl acetate NMR (CDCI3, 5): J .35 (3H, t, J=7Hz), 1.70 (3H, m), 1.94 (3H, s), 2.04 (3H, s), 2.11 (3H, s), 2.78 (2H, m), 3.01 (2H, q, J=7Hz), 3.10 (1H, m), 3.46 (1H, m), 3.62 (1H, t, J=6Hz), 3.79 (1H, d, J=8Hz), 3.98 (2H, m), 4.83 (1H, dd, J=3 and 10Hz), 4.97 (1H, dd, J=8 and 10Hz), 5.28 (1H, d, J=3Hz), 6.02 (1H, d, J=5Hz), 6.64 (1H, d, J=5Hz), 7.31 (1H, m), 7.41-7.56 (8H, m) Example 228 To a solution of (2R,3R,4S,5S,6R)-4--bis(acetyloxy)-6-[(acetyloxy)methyl]-2-{2-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]ethoxy}tetrahydro-2H-pyran-3-yl acetate (113 mg) in methanol (2 mL) was added sodium methoxide (0.86 mg) at room temperature. After stirring for 2 hours, the solvent was evaporated off, and the mixture was partitioned between ethyl acetate (20 mL) and water (10 mL). The organic layer was washed with brine, dried over magnesium sulfate, and evaporated to give an yellow foam (77.3 mg). The foam was triturated in hexane to give (2R,3R,4S-R,6R)-2-{2-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]ethoxy}-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol as an yellow powder (48.3 mg,89.7%). (2R,3R,4S-R,6R)-2-{2-[4-(3-Chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]ethoxy}-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol NMR (CDCI3,8): 1.36 (3H, t, J=7Hz), 1.92 (1H, m), 2.06 (1H, m), 2.56 (1H, s, br), 2.76-2.92 (3H, m), 3.02 (2H, q, J=7Hz), 3.24 (2H, m), 3.38-3.50 (3H, m), 3.63-3.84 (3H, m), 2.41 (1H, s, br), 6.01 (1H, d, J=5Hz), 6.63 (1H, d, J=5Hz), 7.32 (1H, m), 7.41-7.57 (8H,m) The following compounds were obtained in substantially the same manner as that of Example 228. Example 229 3-[4-(3-Chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]-N-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]propanamide NMR (CDCI3,5): 1.38 (3H, t, J=7Hz), 1.97 (2H, m), 2.83 (2H, m), 3.01 (2H, q, J=7Hz), 3.31-3.52 (3H, m), 3.61-3.76 (2H, m), 3.88 (1H, m), 4.63 (1H, d, J=9Hz), 6.01 (1H, d, J=5Hz), 6.64 (1H, d, J=5Hz), 7.34 (1H, m), 7.42-7.59 (8H, m) Example 230 Ethyl 5-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(hydroxyrnethyl)pyrrolo[l,2-b]pyrida2in-3-yl]pentanoate from ethyl 5-[2-[(acetyloxy)methyl]-4-(5-brorno-3-pyridinyl)-7-ethylpyrrolo[ 1,2-b]pyridazin-3-yl]pentanoate NMR (CDC13,5): 1.24 (3H, t, J=7Hz), 1.34-1.50 (5H, m), 1.54 (2H, m), 2.19 (2H, t, J=7Hz), 2.37 (2H, m), 3.02 (2H, q, J=7Hz), 3.71 (1H, t, J=5Hz), 4.10 (2H, q, J=7Hz), 4.86 (2H, d, J=5Hz), 5.97 (1H, d, J=5Hz), 6.60 (1H, d, J=5Hz), 7.88 (1H, m), 8.55 (1H, m), 8.79 (lH,m) Example 231 To a solution of 5-[4-(3-cyanophenyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid (50 mg) in N,N-dimethylfoimamide (1 mL) was added 1,1 -carbonyldiimidazole (33.6 mg) at ambient temperature. After 1 hour stirring, to the mixture was added methanesulfonamide (19.7 mg) and l,8-diazabicyclo[5.4.0]undec-7-ene (31.6 mg). The mixture was heated at 50°C for 2 hours. The reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was acidified with IN hydrogen chloride and was extracted with ethyl acetate. The organic layer was washed with water 3 times and brine, dried over magnesium sulfate, and evaporated in vacuo to give an yellow solid. The residue was crystallized from IPE to give yellow solid (45 mg). The solid was recrystallized from ethanol to give N-{5-[4-(3-cyanophenyl)-7-ethyI-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoyl}methanesulfonamide (25 mg,) as an yellow solid. N-{5-[4-(3-Cyanophenyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoyl}methanesulfonamide NMR (CDCI3,5): 1.33-1.61 (7H,m),2.21 (2H,t, J=8Hz), 2.40 (2H,t, J=8Hz), 2.55 (3H, s), 3.00 (2H, q, J=8Hz), 3.29 (3H, s), 5.80 (1H, d, J=5Hz), 6.52 (1H, d, J=5Hz), 7.58-7.67 (3H, m), 7.76 (1H, m), 7.86 (1H, br s) MS(ESI+):m/z439(M+H) Example 232 To a solution of ethyl 5-[4-(3-cyanopheny])-7-ethyI-2-melhyJpyrroIo[l,2-bJpyridazin-3-yl]pentanoate (45 mg) in tetrahydrofuran (1 mL) was added lithium borohydride (5 mg) in an ice-water bath. Then the reaction mixture was stirred at ambient temperature. After 2 hours, another lithium borohydride (5 mg) was added therein and was stirred overnight. The reaction mixture was partitioned between ethyj acetate and water. The organic layer was washed with brine, dried over magnesium sulfate, and was evaporated in vacuo. The residue was purified by p-TLC (hexane-elhyl acetate = 1-1) to give 3-[7-ethyl-3-(6-hydroxyhexyl)-2-methylpyrrolo[l,2-b]pyridazin-4-yl]benzonitrile (26 mg, 64.5%) as an yellow oil and 6-{4-[3-(aminomethyl)phenyl]-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl}-l-hexanol (13 mg, 31.9%) as a yello solid. 3-[7-Ethyl-3-(6-hydroxyhexyl)-2-methylpyrrolo[l,2-b]pyridazin-4-yl]benzonitrile NMR (CDC13,8): 1.15-1.53 (11H, m), 2.32-2.41 (2H, m), 2.56 (3H, s), 3.01 (2H, q, J=8Hz), 3.58 (2H, br t, J=8Hz), 5.58 (1H, br t, J=8Hz), 5.79 (1H, d, J=5Hz), 6.51 (lH3d,J=5Hz), 7,57-7.63 (2H,m),7.65 (1H, brs), 7.75 (lH,m) MS(ESI+):m/z362(M+H) 6-{4-[3-(Aminomethyl)phenyl]-7-ethyl-2-methylpyrrolo[l32-b]pyridazin-3-yl}-l-hexanol NMR (CDC13,8): 1.03-1.43 (11H, m), 2.41 (2H, t, J=8Hz), 2.55 (3H, s), 3.01 (2H, q, J=8Hz), 3.39-3.61 (2H, m), 3.88-4.04 (2H, m), 4.25 (2H, br s), 5.31 (1H, d, J=5Hz), 6.49 (1H, d, J=5Hz), 7.28-7.40 (3H, m), 7.51 (1H, t, J=8Hz) MS(ESI+):m/z366(M+H) Ex-mEil233 To a suspension of 6.{4-[4-(ammocarbonyl)phenyl]-7-elhyl-2-rae,hylpyrroIo[l,2- Mpyndazin-3-yl1Hexanoic acid (590 mg) in wa.e, (3 mL) was added IN sodium bydroxide (li -P a. ambien, temperafure. Ate 5 hours, .he mixure became dear sLion The soiu.ion was ffl.ered ,h,ough membrane finer, washed w„h wa,er (0.4 mL and was freezedned for 15 hours ,o give 6-,4-[4-(ami„ocarbonyl)pheny1]-7-e,hyl-2-acid sodium sa>, (6,2 mg, 98,%) as a pa,e yellow powder. 6-{4-[4-(Aminocarbonyl)phenyl]-7 acid sodium salt NMR (DMSO-d6,5): 1.10-1.15 (2H, m), 1.20-1.40 (7H, m), 1.74 (2H, t, J=8Hz), 2.25-2.38 (2H, m), 2.50 (3H, s), 2.91 (2H, q, J=8Hz), 5.72 (1H, d, J=5Hz), 6.50 (1H, d, J=5Hz), 7.39-7.46 (3H, m), 7.97 (2H, d, J=8Hz), 8.26 (1H, br s) Example 234 A solution of 5-[4-(3-cyanophenyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid (100 mg), triethylamime (29.4 mg), and diphenylphosphoryl azide (79.9 mg) in tert-butanol (2 mL) was heated at 80°C for 8 hours. The cooled reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by p-TLC (hexane-ethyl acetate = 3-1) to give tert-butyl 4-[4-(3-cyanophenyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]butylcarbamate (28 mg, 23.4%) as an yellow oil. tert-Butyl4-[4-(3-cyanophenyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]butylcarbamate NMR(CDC13,5): 1.27-1.47 (14H,m), 2.34-2.45 (2H,m),2.55 (3H,s), 2.91-3.02 (4H, m), 4.39 (1H, br s), 5.79 (1H, d, J=5Hz), 6.51 (1H, d5 J=5Hz), 7.56-7.67 (3H, m),7.75(lH,m) MS(ESI+):m/z433(M+H) Example 235 To tert-butyl 4-[4-(3-cyanophenyl)-7-ethyl-2-methylpyrrolo[l ,2-b]pyridazin-3-yl]butylcarbamate (25 mg) was added 4N hydrogen chloride in ethyl acetate (1 mL) at ambient temperature. After 1 hour, the mixture was evaporated in vacuo. The residue was triturated with isopropyl ether to give 3-[3-(4-aminobutyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-4-yl]benzonitrile hydrochloride as dark green amorphous (18 mg). 3-[3-(4-Aminobutyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-4-yl]benzonitrile hydrochloride NMR (CDCI3, 8): 1.27-1.47 (14H, m), 2.34-2.45 (2H, m), 2.55 (3H, s), 2.91-3.02 (4H, m), 4.39 (1H, br s), 5.79 (1H, d, J=5Hz), 6.51 (1H, d, J=5Hz), 7.56-7.67 (3H, m),7.75(lH,m) MS(ESI+):m/z333(M+H) Example 236 To lithium chloride (16.5 mg) was added a solution of ethyl 5-[4-(2-chloro-4-pyridinyl)-7-ethyl-2- methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate (65 mg) and tributyl(vinyl)stannane (56.7 mg) in dioxane (1 mL) and tetrakis(triphenylphosphine)palladium(0) (1.9 mg). The mixture was refluxed. After 4 hours, tributyl(vinyl)stannane (50 mg) and tetrakis(triphenylphosphine)palladium(0) (1.9 mg) was added. After refluxed overnight, the reaction mixture was quenched with potassium fluoride (1.8 mmol) in H2O. The mixture was filtered through Celite and was washed with ethyl acetate. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by flash silica gel chromatography (silica gel, 50 mL) eluted with hexane-ethyl acetate = 5-1 and 3-1 to give ethyl 5-[7-ethyl-2-methyl-4-(2-vinyl-4-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate (18 mg, 28.3%) as an yellow oil. Ethyl 5-[7-ethyl-2-methyl-4-(2-vinyl-4-pyridinyI)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDCI3, 5): 1.15-1.70 (10H, m), 2.18 (2H, t, J=8Hz), 2.36-2.46 (2H, m), 2.55 (3H, s), 3.00 (2H, q, J=8Hz), 4.08 (2H, q, J=8Hz), 5.54 (1H, d, J=10Hz), 5.86 (1H, d, J=5Hz), 6.25 (1H, d, J=16Hz), 6.51 (1H, d, J=5Hz), 6.87 (1H, dd, J=16,10Hz), 7.16 (1H, dd, J=6,1Hz), 7.33 (1H, br s), 8.70 (1H, d, J=6Hz) MS (ESI+): m/z 392 (M+H) The following compounds were obtained in substantially the same manner as that of Example 236. Example 237 Ethyl 5-{4-[5-(l-ethoxyvinyl)-3-pyridinyl]-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl}pentanoate NMR (CDCI3, 6): J .23 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.42 (3H, t, J=7Hz), 1.40-1.60 (4H, m), 2.20 (2H, t, J=7Hz), 2.38-2.52 (2H, m), 2.56 (3H, s), 3.03 (2H, q, J=7Hz), 3.96 (2H, q, J=7Hz), 4.09 (2H, q, J=7Hz), 4.34 (1H, d, J=2Hz), 4.76 (1H, d, J=2Hz), 5.87 (1H, d, J=4Hz), 6.52 (1H, d, J=4Hz), 7.89 (1H, m), 8.53 (1H, d,J=2Hz),8.93(lH,d,J=2Hz) MS:(m/z)436(M+H) Example 238 Ethyl 5-[7-ethyl-2-methyl-4-(5-vinyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDC13, 8): 1.22 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.40-1.65 (4H, m), 2.18 (2H, t, J=7Hz), 2.40-2.53 (2H, m), 2.56 (3H, s), 3.02 (2H, q, J=7Hz), 4.08 (2H, q, J=7Hz), 5.43 (1H, d, J=llHz), 5.88 (1H, d, J=4Hz), 5.89 (1H, d, J=18Hz), 6.52 (1H, d, J=4Hz), 6.71-6.83 (1H, dd, J=ll Hz, 18Hz), 7.73 (1H, m), 8.47 (1H, d, J=2Hz), 8.68 (1H, d, J=2Hz) Example 239 Ethyl 5-[7-ethyl-2-(methoxymethyl)-4-(5-vinyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3- yl]pentanoate NMR (CDCI3, 5): 1.22 (3H, t, J=7Hz), 1.38 (3H, t, J=7Hz), 1.40-1.60 (4H, m), 2.17 (2H, t, J=7Hz), 2.52-2.65 (2H, m), 3.04 (2H, q, J=7Hz), 3.46 (3H, s), 4.08 (2H, q, J=7Hz), 4.63 (2H, s), 5.43 (1H, d, J=llHz), 5.88 (1H, d, J=18Hz), 5.91 (1H, d, J=4Hz), 6.58 (1H, d, J=4Hz), 6.71-6.83 (1H, dd, J=ll Hz, 18Hz), 7.75 (1H, m), 8.49 (1H, d, J=2Hz), 8.71 (1H, d, J=2Hz) Example 240 Ethyl 5-[4-[5-(l-ethoxyvinyl)-3-pyridinyl]-7-ethyl-2-(methoxymethyl)pyrrolo[l,2- b]pyridazin-3-yl]pentanoate NMR (CDCI3, 5): 1.22 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.42 (3H, t, J=7Hz), 1.40-1.63 (4H, m), 2.18 (2H, t, J=7Hz), 2.51-2.63 (2H, m), 3.03 (2H, q, J=7Hz), 3.47 (3H, s), 3.93 (2H, q, J=7Hz), 4.12 (2H, q, J=7Hz), 4.35 (1H, d, J=3Hz), 4.63 (2H, s), 4.77 (1H, d, J=3Hz), 5.92 (1H, d, J=4Hz), 6.58 (1H, d, J=4Hz), 7.92 (1H, m), 8.53 (1H, d, J=2Hz), 8.93 (1H, d, J=2Hz) MS(ESl+):m/z466 Example 241 Ethyl 5-[7-ethyl-2-phenyl-4-(5-vinyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]penlanoate NMR (CDCI3, 5): 1.15-1.31 (7H, m), 1.37 (3H, t, J=7Hz), 1.87 (2H, t, J=7Hz), 2.43 (2H, m), 3.01 (2H, q, J=7Hz), 3.98 (2H, q, J=7Hz), 5.45 (1H, d, J=l 1Hz), 5.88 (lH,d,J=18Hz), 5.98 (lH,d,J=5Hz), 6.62 (lH,d,J=5Hz), 6.78 (lH,dd,J=ll and 18Hz), 7.44-7.55 (5H, m), 7.81 (1H, m), 8.55 (1H, m), 8.72 (1H, m) Example 242 A solution of 5-[4-(2-chloro-4-pyridinyl)-7-ethyl-2-methylpyrrolo[l ,2-b]pyridazin-3-yl]pentanoic acid (50 mg) in dioxane (1.5 mL) in a sealed tube was added 50% dimethylamine in water (1.5 mL). The mixture was heated at 175°C overnight. The cooled reaction mixture was concentrated in vacuo. The residue was dissolved in water (1 mL) and the pH was adjusted to 7-8. The mixture was extracted with chloroform three times. The organic layer was dried over magnesium sulfate and evaporated in vacuo. The residue was purified by flash silica gel chromatography (silica gel, 50 mL) eluted with chloroform-ethyl acetate = 1-1 and chloroform-methanol = 20-1 to give yellow oil (43 mg). The oil was crystallized from isopropyl ether to give 5-{4-[2-(dimethylamino)-4-pyridinyl]-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl}pentanoic acid as an yellow solid (27 mg, 52.8%). 5-{4-[2-(Dimethylamino)-4-pyridinyl]-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl}pentanoic acid NMR (CDCI3,5): 1.36 (3H, t, J=8Hz), 1.40-1.65 (4H, m), 2.25 (2H, t, J=8Hz), 1.86- 1.96 (2H, m), 2.55 (3H, s), 3.00 (2H, q, J=8Hz), 4.08 (2H, q, J=8Hz), 5.54 (1H, d, J=10Hz), 5.86 (1H, d, J=5Hz), 6.25 (1H, d, J=16Hz), 6.51 (1H, d, J=5Hz), 6.87 (1H, dd, J=16,10Hz), 7.16 (1H, dd, J=651Hz), 7.33 (1H, br s), 8.70 (1H, d, J=6Hz) Example 243 To a suspension of 7-chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazine-3-carbaldehyde (40 mg) in ethanol (1 mL) was added 2-aminoelhanol (11.8 mg), sodium cyanoborohydride (12.1 mg), and acetic acid (1 drop) in an ice-water bath. After 10 minutes, the mixture was stirred at ambient temperature. After 2 hours, sodium cyanoborohydride (11.8 mg) was added and the reaction mixture was acidified to pH4 with acetic acid (5 drops). After stirring overnight, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with saturated sodium bicarbonate, water, and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by p-TLC (chloroform-methanol = 10-1) to give 2-({[7-chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazin-3-yl]methyl}amino)ethanol as pale yellow oil (21 mg). 2-({[7-Chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazin-3-yl]methyl}amino)ethanol NMR (CDC13, 8): 1.43 (6H, d, J=7Hz), 2.65 (2H, t, J=7Hz), 342 (1H, m), 3.53 (2H, t, J=7Hz), 3.59 (2H, s), 6.01 (1H, d, J=5Hz), 6.77 (1H, d, J=5Hz), 7.14-7.24 (2H, m), 7.35-7.44 (2H,m) MS (ESI+): m/z 362 (M+H) Example 244 To a solution of [4-(4-fluorophenyl)-2-methylpyrrolo-[l,2-b]pyridazin-3-yI]methanol (505 mg) and triethylamine (997 mg) in dichloromethane (4 mL) and dimethyl sulfoxide (2 mL) was added sulfur trioxide pyridine complex (941 mg) in an ice-water bath under nitrogen. After 30 minutes, the mixture was stirred at ambient temperature for 2 hours. The reaction mixture was concentrated to about 1/3 volume. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with water three times and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by flash silica gel chromatography (silica gel, 30 mL) eluted with hexane-chloroform = 3-1 and 2-1 to give 4-(4-fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazine-3-carbaldehyde as an yelow solid (340 mg, 67.9%). 4-(4-Fluorophenyl)-2-methylpyrrolo[l,2-b]pyridazine-3-carbaldehyde NMR (CDCI3,6): 2.77 (3H, s), 6.50 (1H, m), 6.86 (1H, m), 7.20-7.30 (2H, m), 7.44- 7.54 (2H, m), 8.89 (1H, br s), 9.79 (1H, s) Example 245 A mixture of ethyl 4-(4-fluoropbenyl)-2-isopropyl-7-viny]pyrrolo[l,2-b]pyridazine-3-carboxylate (8.9 g) and 10% palladium on carbon (900 mg) in ethanol (180 mL) was stirred under hydrogen atomosphere (3.5 atm) at ambient temperature. After 10 hours, the mixture was stood overnight. To the mixture was added 10% palladium on carbon (900 mg) and was stirred under hydrogen atomosphere (3.5 atm) at ambient temperature. After 12 hours, the mixture was stood overnight. To the mixture was added 10% palladium on carbon (900 mg) and was stirred under hydrogen atomosphere (3.5 atm) at ambient temperature for 8 hours. The mixture was filtered through Celite. The filtrate was concentrated in vacuo to give ethyl 7-ethyl-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazine-3-carboxylate as an yellow oil (9.0 g, 100.5%). Ethyl 7-ethyl-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazine-3-carboxylate NMR (CDC13,8): 0.96 (3H, t, J=8Hz), 1.38 (3H, t, J=8Hz), 3.05 (2H, q, J=8Hz), 4.01 (2H, q, J=8Hz), 6.27 (1H, d, J=5Hz), 6.64 (1H, d, J=5Hz), 7.10-7.19 (2H, m), 7.41-7.49 (2H,m) MS(ESI+):m/z362(M+H) The following compounds were obtained in substantially the same manner as that of Example 245. Example 246 5-[7-Elhyl-4-(5-ethyl-3-pyridinyl)-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoicacid from5-[7-ethyl-2-methyl-4-(5-vinyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3,5): 1.30 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.45-1.65 (4H5 m), 2.22 (2H, m), 2.35-2.50 (2H, m), 2.56 (3H, s), 2.75 (2H, q, J=7Hz), 3.00 (2H, q, J=7Hz), 5.84 (1H, d, J=4Hz), 6.52 (1H, d, J=4Hz), 7.57 (1H, s), 8.42 (1H, d, J=2Hz),8.53(lH,d,J=2Hz) MS (ES1+): m/z 366 (M+H), MS (ESI'): m/z 364 Rxample 247 547-Ethyl-4-(5-ethyl-3-pyridinyl)-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3- yl]pentanoic acid NMR(CDC13,8): 130 (3H,t,J=7Hz),l.37 (3H,t,J=7Hz), 1.45-1.64 (4H,m),2.17 (2H, m), 2.45-2.67 (2H, m), 2.73 (2H, q, J=7Hz), 3.04 (2H, q, J=7Hz), 3.45 (3H, s), 4.62 (2H, m), 5.89 (1H, d, J=4Hz), 6.58 (1H, d, J=4Hz), 7.59 (1H, s), 8.44 (1H, s),854(lH,s) MS (ESI+): m/z 396 Example 248 Ethyl 5-[7-ethyl-4-(5-ethyl-3-pyridinyl)-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR(CDC13,5): 1.04-1.23 (7H,m), 132 (3H, t, J=7Hz), 137 (3H,t,J=7Hz), 1.86 (2H,1, J=7Hz), 2.42 (2H, m), 2.74 (2H, q, J=7Hz), 3.01 (2H, q, J=7Hz), 3.99 (2H, q, J=7Hz), 5.97 (1H, d, J=5Hz), 6.62 (1H, d, J=5Hz), 7.45-7.53 (5H, m), 7.60 (1H, m), 8.50 (1H, m), 8.56 (1H, m) Example 249 To a solution of 3-(7-ethyl-2-neopentylpyrrolo[l,2-b]pyridazin-4-yl)benzamide (35 mg) in ethanol (1 mL) was added water (0.2 mL) and potassium hydroxide (68.9 mg) at ambient temperature. The reaction mixture was heated at 60°C. After 2 hours, potassium hydroxide (100 mg) was added. After 5 hours, potassium hydroxide (100 mg) was added. After 12 hours, the mixture was acidified with IN hydrogen chloride. The precipitate was filtered, washed with water and ethyl acetate to give 3-(7-ethyl-2-neopentylpyrrolo-[l,2-b]pyridazin-4-yl)benzoic acid as an yellow solid (19 mg, 54.1%). 3-(7-Ethyl-2-neopentylpyrrolo[l ,2-b]pyridazin-4-yl)benzoic acid NMR (CDC13,5): 1.05 (9H, s), 1.39 (3H, t, J=8Hz), 2.69 (2H, s), 3.04 (2H, q, J=8Hz), 6.42 (1H, s), 6.54 (1H, d, J=5Hz), 6.65 (1H, d, J=5Hz), 7.62 (1H, t, J=8Hz), 7.97 (1H, d, J=8Hz), 8.21 (1H, d, J=8Hz), 8.46 (1H, br s) MS(ESI+):m/z337(M+H) The following compound was obtained in substantially the same manner as that of Example 249. Example 250 3-[7-Ethyl-2-(2-furyl)pyrrolo[l,2-b]pyridazin-4-y]]ben2oic acid NMR (CDCI3, 5): J .44 (3H, t, J=8Hz), 3.11 (2H, q, J=8Hz), 6.56 (1H, m), 6.61 (1H, d,J=5Hz), 6.72 (lH,d,J=5Hz), 7.03 (lH,brs), 7.07 (lH,d,J=5Hz), 7.55-7.69 (2H, m), 8.03 (1H, br d, J=8Hz), 8.23 (1H, br d, J=8Hz), 8.52 (1H, br s) Example 251 A solution of ethyl 5-{4-[5-(l-ethoxyvinyl)-3-pyridinyl]-7-ethyI-2-methylpyrrolo[l,2-b]pyridazin-3-yl}pentanoate (190 mg) in methanol (5 mL) and IN hydrochloric acid (5 mL) was stirred at ambient temperature for 2 hours. The solution was diluted with brine and extracted with chloroform. The organic layer was separated, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and ethyl acetate (10:1 - 2:1) to give ethyl 5-[4-(5-acetyl-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate as an yellow oil (160 mg). Ethyl 5-[4-(5-acetyl-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDCI3,5): 1.24 (3H, t, J=7Hz), 1.38 (3H, t, J=7Hz), 1.40-1.60 (4H, m), 2.19 (2H, t, J=7Hz), 2.36-2.47 (2H, m), 2.57 (3H, s), 2.70 (3H, s), 3.02 (2H, q, J=7Hz), 4.08 (2H, q, J=7Hz), 5.81 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 8.23 (1H, m), 8.78 (1H, d, J=2Hz), 9.23 (1H, d, J=2Hz) MS:(m/z)408(M+H) The following compound was obtained in substantially the same manner as that of Example 251. Example 252 Ethyl 5-[4-(5-acetyl-3-pyridinyl)-7-ethyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDCI3, 5): 1.24 (3H, t, J=7Hz), 1.38 (3H, t, J=7Hz), 1.40-1.59 (4H, m), 2.17 (2H, t, J=7Hz), 2.50-2.63 (2H, m), 2.70 (3H, s), 3.03 (2H, q, J=7Hz), 3.46 (3H, s), 4.12 (2H, q, J=7Hz), 4.63 (2H, s), 5.86 (1H, d, J=4Hz), 6.59 (1H, d, J=4Hz), 8.26 (lH,m), 8.79 (lH,d,J=2Hz), 9.24 (lH,d,J=2Hz) MS(ESI+):m/z438 Example 253 To a solution of ethyl 5-{4-(2-chloro-4-pyridinyl)-7-ethyl-2-[(methylthio)methyl]pyrrolo[l,2-b]pyridazin-3-yl}pentanoate (139 mg) in tetrahydrofuran (4 rnL) and water (1 mL) was added oxone (287 mg) and the mixture was stirred at ambient temperature for 4 hours. The solution was diluted with water and extracted with ethyl acetate. The organic layer was separated, washed with saturated sodium bicarbonate solution, sodium thiosulfate solution and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and ethyl acetate (10:1 -1:1) to give ethyl 5-{4-(2-chloro-4-pyridinyl)-7-ethyl-2-[(methylsulfonyl)methyl]pyrrolo[l,2-b]pyridazin-3-yl}pentanoate as an yellow oil (124 mg). Ethyl5-{4-(2-chloro-4-pyridinyl)-7-ethyl-2-[(methylsulfonyl)methyl]pyrrolo[l,2-b]pyridazin-3-yl}pentanoate NMR (CDC13, 5): 1.24 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.40-1.63 (4H, m), 2.21 (2H, t, J=7Hz), 2.57-2.68 (2H, m), 3.02 (2H, q, J=7Hz), 3.12 (3H, s), 4.10 (2H, q, J=7Hz), 4.53 (2H, s), 5.98 (1H, d, J=4Hz), 6.68 (1H, d, J=4Hz), 7.27 (1H, m), 7.38 (1H, s), 8.56 (1H, d, J=5Hz) Example 254 A mixture of ethyl 5-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate (167 mg) and copper(I) cyanide (37 mg) in l-methyl-2-pyrrolidinone (3 mL) was stirred at 170°C for 4 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and ethyl acetate (20:1 - 5:1) to give ethyl 5-[4-(5-cyano-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate as an yellow oil (88 mg). Ethyl 5-[4-(5-cyano-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDCI3,8): 1.24 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.40-1.62 (4H, m), 2.2] (2H, t, J=7Hz), 2.35-2.47 (2H, m), 2.57 (3H, s), 3.02 (2H, q, J=7Hz), 4.12 (2H, q, J=7Hz), 5.79 (1H, d, J=4Hz), 6.54 (1H, d, J=4Hz), 7.98 (1H, m), 8.80 (1H, d, J=2Hz),8.97(lH,d,J=2Hz) MS(ESI+):m/z391. The following compounds were obtained in substantially the same manner as that of Example 254. Example 255 5-[4-(5-Cyano-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3,8): 1.37 (3H, t, J=7Hz), 1.40-1.67 (4H, m), 2.28 (2H, m), 2.37-2.47 (2H, m), 2.57 (3H, s), 3.01 (2H, q, J=7Hz), 5.80 (1H, d, J=4Hz), 6.55 (1H, d, J=4Hz), 8.01 (1H, s), 8.81 (1H, br), 8.98 (1H, br) Example 256 Ethyl 5-[4-(5-cyano-3-pyridinyl)-7-ethyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3- yl]pentanoate NMR (CDCI3,8): 1.23 (3H, t, J=7Hz), 1.37 (3H, t, J=7Hz), 1.40-1.60 (4H, m), 2.19 (2H, t, J=7Hz), 2.49-2.60 (2H, m), 3.04 (2H, q, J=7Hz), 3.46 (3H, s), 4.12 (2H, q, J=7Hz), 4.63 (2H, s), 5.84 (1H, d, J=4Hz), 6.63 (1H, d, J=4Hz), 8.02 (1H, m), 8.83 (1H, d, J=2Hz), 8.98 (1H, d, J=2Hz) Example 257 5-[4-(5-Cyano-3-pyridinyl)-7-ethyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3,8): 1.38 (3H, t, J=7Hz), 1.40-1.65 (4H, m), 2.27 (2H, t, J=7Hz), 2.48- 2.64 (2H, m), 3.03 (2H, q, J=7Hz), 3.46 (3H, s), 4.64 (2H, s), 5.84 (1H, d, J=4Hz), 6.62 (1H, d, J=4Hz), 8.03 (1H, s), 8.82 (1H, s), 8.97 (1H, s) Example 258 5-[4-(5-Cyano-3-pyridinyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid NMR (CDCI3,8): 1.06-1.24 (4H, m), 1.36 (3H, t, J=7Hz), 1.94 (2H, t, J=7Hz), 2.38 (2H, m), 2.99 (2H, q, J=7Hz), 5.88 (1H, d, J=5Hz), 6.64 (1H, d, J=5Hz), 7.44-7.52 (5H, in), 8.06 (1H, s), 8.87 (1H, s), 8.98 (1H, s) MS(ESI+):m/z425(M+H) Example 259 To a suspension of lithium aluminum hydride (98.8 mg) in tetrahydrofuran (10 mL) was added ethyl 5-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate (600 mg) in tetrahydrofuran (10 mL) under ice-water cooling and the mixture was stirred at 0°C for 2 hours. The reaction was quenched with saturated potassium sodium tartrate solution and the insolubles were filtereed off and washed with ethyl acetate. The filtrates were washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and ethyl acetate (10:1 - 2:1) to give 5-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]-l-pentanol as an yellow oil (478 mg). 5-[4-(3-ChlorophenyI)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]-l-pentanol NMR (CDC13,5): 0.90-1.22 (6H, m), 1.27 (1H, t, J=7Hz), 1.36 (3H, t, J=7Hz), 2.37- 2.47 (2H, m), 3.02 (2H, q, J=7Hz), 3.29-3.41 (2H, m), 5.97 (1H, d, J=4Hz), 6.61 (1H, d, J=4Hz), 7.32 (1H, m), 7.40-7.55 (8H, m) Example 260 To a solution of 5-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]-l-pentanol (63.0 mg) and triethylamine (22.8 mg) in dichloromethane (3 mL) was added methanesulfonyl chloride (18.9 mg) under ice-water cooling and the mixture was stirred at 0°C for 1 hour. The solution was washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was added to sodium cyanide (14.7 mg) in dimethylformamide (2 mL) and the mixture was stirred at 60°C for 5 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and ethyl acetate (20:1 - 5:1) to give 6-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[ 1,2-b] pyridazin-3-yl1Hexanenitrile as an yellow oil (58.5 mg). 6-[4-(3-chlorophenyl)-7-ethyl-2-pheny]pyrrolo[l,2-b]pyridazin-3-yl1Hexaneni(rile NMR (CDCI3, 5): 1.00-1.15 (4H> m), 1.17-1.28 (2H, m), 1.36 (3H, t, J=7Hz), 1.98 (2H, t, J=7Hz), 2.38-2.47 (2H, m), 3.03 (2H, q, J=7Hz), 5.99 (1H, d, J=4Hz), 6.62 (1H, d, J=4Hz), 7.32 (1H, m), 7.38-7.56 (8H, m) MS(ESI+):m/z428 Example 261 A mixture of 5-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l ,2-b]pyridazin-3-yl]-l-pentanoI (65 mg), trimethyloxonium tetrafluoroborate (27.5 mg) and 2,6-di-t-butyl-4-methylpyridine (47.8 mg) in 1,2-dichloroethane (3 mL) was stirred at ambient temperature for 4 hours. The solution was washed with water, IN hydrochloric acid, water, saturated sodium bicarbonate solution and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and ethyl acetate (20:1 - 5:1) to give 4-(3-chlorophenyl)-7-ethyl-3-(5-methoxypentyl)-2-phenylpyrrolo[l,2-b]pyridazine as an yellow oil (60 mg). 4-(3-chlorophenyl)-7-ethyl-3-(5-methoxypentyl)-2-phenylpyrrolo[l,2-b]pyridazine NMR (CDCI3,8): 00.90-132 (6H, m), 1.36 (3H, t, J=7Hz), 2.37-2.47 (2H, m), 3.03 (2H, q, J=7Hz), 3.08 (2H, t, J=7Hz), 3.31 (3H, s), 5.97 (1H, d, J=4Hz), 6.61 (1H, d, J=4Hz), 7.27-7.33 (1H, m), 7.38-7.53 (8H, m) MS (ES1+): m/z 433 Example 262 To a solution of 5-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]-l-pentanol (55 mg) and triethylamine (19.9 mg) in dichloromethane (3 mL) was added methanesulfonyl chloride (16.5 mg) under ice-water cooling and the mixture was stirred at 0°C for 1 hour. The solution was washed with brine, dried over magnesium sulfate, and evaporated in vacuo. To the residue in 1,2-dichloroethane (3 mL) was added 2 M dimethylamine in tetrahydrofuran (3 mL) and the mixture was stirred at 60°C for 120 hours. The solution was diluted with chloroform, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture ofhexane and ethyl acetate (20:1 - 5:1) to give 5-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[],2-b]pyridazin-3-yl]-N,N-dimethyl-1-pentanamine as an yellow oil (38 mg). N-{5-[4-(3-Chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]pentyl}-N,N-dimethylamine NMR (CDC13,5): 0.86-0.97 (2H, m), 1.02-1.15 (4H, m), 1.36 (3H, t, J=7Hz), 1.97- 2.04 (2H, m), 2.11 (6H, s), 2.37-2.47 (2H, m), 3.02 (2H, q, J=7Hz), 5.97 (1H, d, J=4Hz), 6.61 (1H, d3 J=4Hz), 7.31 (1H, m), 7.39-7.54 (8H, m) MS(ESI+):m/z446 Example 263 To a stirred solution of 5-[4-(3-cyanophenyl)-7-elhyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid (60 mg) in dichloromethane (2 ml) was added l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (35.3 mg) and 2-animopyridine (20 mg) and the reaction mixture was stirred for 10 minutes. 4-Dimethylaminopyridine (2 mg) was added and the reaction mixture was stirred at room temperature for 15 hours. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a mixture of ethyl acetate and n-hexane (1:2) to give5-[4-(3-cyanophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]-N-(2-pyridinyl)pentanamide(55.7mg) as an yellow amoiphous. 5-[4 NMR (CDCI3,5): 1.12 (2H, quintet, J=7Hz), 1.30 (2H, quintet, J=7Hz), 1.36 (3H, t, J=7Hz), 1.95 (2H, t, J=7Hz), 243 (2H, q, J=7Hz), 3.02 (2H, q, J=7Hz), 5.90 (1H, d, J=4Hz), 6.62 (1H, d, J=4Hz), 7.00-7.05 (1H, m), 7.43-7.54 (5H, m), 7.59-7.77 (6H5 m), 8.11 (1H, d, J=7.5Hz), 8.24 (1H, d, J=4Hz) MS:(m/z)499(M+),45(bp) The following compounds were obtained in substantially the same manner as that )f Example 263. Example 264 5-[4-(3-Chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]-N-(2-pyridinyl)pentanamide NMR (CDCI3,8): 1.15 (2H, quintet, J=7Hz), 1.24(2H, quintet, J=7Hz), 1.36(3H, t, J=7Hz), 1.91(2H, t, J=7Hz), 2.45(2H, t, J=7Hz), 3.00(2H, q, J=7Hz), 5.97(1H, d, J=5Hz), 6.60(1H, d, J=4Hz), 7.00(1H, t, J=7Hz), 7.30(1H, s), 7.38-7.53(7H, m), 7.65-7.73(2H, m), 8.11(1H, d, J=7Hz), 8.25(1H, d, J=5Hz) MS: (m/z) 509 (M++H), 74 (bp) Example 265 N-{5-[4-(3-Chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3- yl]pentanoyl}methanesulfonamide NMR (CDCI3,6): 1.08 (2H, quintet, J=7Hz), 1.23 (2H, quintet, J=7Hz), 1.36 (3H, t, J=7Hz), 1.85 (2H, t, J=7Hz), 2.44 (2H, t, J=7Hz), 3.02 (2H, q, J=7Hz), 3.21 (3H, s), 5.99 (1H, d, J=4Hz), 6.62 (1H, d, J=4Hz), 7.30-7.33 (1H, m), 7.43-7.55 (8H, m) Example 266 5-[4-(2-chloro-4-pyridinyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]-N-(2-pyridinyl)pent anamide NMR (CDCI3,5): 1.12 (2H, quintet, J=7Hz), 1.27 (2H, quintet, J=7Hz), 1.36 (3H, t, J=7Hz), 1.97 (2H, t, J=7Hz), 2.45 (2H, t, J=7Hz), 3.01 (2H, q, J=7Hz), 5.95 (1H, d, J=5Hz), 6.63 (1H, d, J=4Hz), 7.01 (1H, t, J=7Hz), 7.31 (1H, d, J=7Hz), 7.41-7.53 (6H, m), 7.68 (1H, ddd, J=7,7,lHz), 7.77 (1H, s), 8.12 (1H, d, J=7.5Hz), 8.24 (1H, d, J=5Hz), 8.53 (1H, d, J=6Hz) MS: (m/z) 510 (M++H), 80 (bp) Example 267 N-{5-[4-(5-Bromo-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3- yl]pentanoyI}melhanesulfonamide mp: 124-125°C NMR (CDC13, 5): 1.37 (3H, t, J=7Hz), 1.43-1.49 (2H, m), 1.55-1.65 (2H, m), 2.23 (2H, t, J=7Hz), 2.34-2.48 (2H, m), 2.55 (3H, s), 3.01 (2H, q, J=7Hz), 3.28 (3H, s), 5.87 (1H, d, J=4Hz), 6.53 (1H, d, J=4Hz), 7.09 (1H, s), 7.40 (1H, s), 8.53 (1H, s), 8.77 (lH,s) MS: (m/z) 493(M+), 491 (M+-2), 137 (bp) Example 268 To a solution of ethyl 5-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(hydroxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate (100.0 mg) and (bromomethyl)benzene (111 mg) in N,N-dimethylformamide (1 mL) was added 60% sodium hydride (17.4 mg) under an ice-bath. After stirring for 2.5 hour, the reaction was quenched by adding IN hydrochloric acid (1 mL), and the mixture was partitioend between ethyl acetate (10 mL) and water (5 mL). The organic layer was washed with IN hydrochloric acid (5 mL), water (5 mL, three times), and brine, dried over magnesium sulfate, and evaporated. Flash silica gel column chromatography eluting with ethyl acetate-hexane = 1/40 to 20/40 afforded ethyl 5-[2-[(benzyloxy)methyl]-4-(5-bromo-3-pyridinyl)-7-ethylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate as an yellow gum (47.7 mg, 39.9%). Ethyl 5-[2-[(benzyloxy)methyl]-4-(5-bromo-3-pyridinyl)-7-ethylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate NMR (CDC13,5): 1.23 (3H, t, J=7Hz), 1.34-1.48 (5H, m), 2.09 (2H, m), 2.53 (2H, m), 3.04 (2H, q, J=7Hz), 4.07 (2H, J=7Hz), 4.65 (2H, s), 4.72 (2H, s), 5.90 (1H, d, J=5Hz), 6.60 (1H, d, J=5Hz), 7.29-7.38 (5H, m), 7.86 (1H, s), 8.54 (1H, m), 8.77 (lH,m) The following compound was obtained in substantially the same manner as that of Example 268. Example 269 Ethyl 5-(4-(5-bromo-3-pyridinyl)-2-{[(4-cyanobenzyl)oxy]methyl}-7-ethylpyrrolo[l,2-b]pyridazin-3-yl)pentanoate NMR (CDCI3, 5): 1.23 (3H, J=7Hz), ] .35-1.55 (7H, m), 2.12 (2H,1, J=7Hz), 2.57 (2H, m), 3.02 (2H, q, J=7Hz), 4.07 (2H, q, J=7Hz), 4.49 (2H, s), 4.76 (2H, s), 5.93 (1H, d, J=7Hz), 6.62 (1H, d, J=7Hz), 7.48 (2H, d, J=8Hz), 7.65 (2H, d, J=8Hz), 7.86 (1H, m), 8.54 (1H, m), 8.78 (1H, m) Example 270 To a solution of ethyl 5-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-;hydroxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate (200 mg) and triethylamine [65.9 mg) in dichloromethane (2 mL) was added methanesulfonyl chloride (54.7 nig) under an ice-bath. After stirring for 1 hour, the reaction was quenched by adding IN hydrochloric acid (1 mL). The mixrure was partitioned between ethyl acetate (20 mL) and IN hydrochloric acid (5 mL). The organic layer was washed with saturated sodium bicarbonate and brine, dried over magnesium sulfate, and evaporated to give ethyl 5-(4-(5-bromo-3-pyridinyl)-7-ethyl-2-{[(methylsulfonyl)oxy]methyl}pyrrolo[l,2-b]pyridazin-3-yl)pentanoate as an yellow gum (247 mg). Ethyl 5-(4-(5-bromo-3-pyridinyl)-7-ethyl-2-{[(methylsulfonyl)oxy]methyl}pyrrolo[l,2-b]pyridazin-3-yl)pentanoate NMR (CDCI3, 5): 1.22 (3H, t, J=7Hz), 1.344.65 (7H, m), 2.20 (2H, t, J=7Hz), 2.55 (2H, m), 3.02 (2H, q, J=7Hz), 3.15 (3H, s), 4.07 (2H, q, J=7Hz), 5.42 (2H, s), 5.99 (1H, d, J=5Hz), 6.68 (1H, d, J=5Hz), 7.87 (1H, m), 8.54 (1H, m), 8.81 (1H, m) Example 271 A mixture of ethyl 5-(4-(5-bromo-3-pyridinyl)-7-ethyl-2-{[(methylsulfonyl)oxy]methyl}pyrrolo[l,2-b]pyridazin-3-yl)pentanoate (50.0 mg), benzyl amine (29.8 mg) in dichloromathane (1 mL) was stirred for 20 hour at room temperature. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried, and evaporated. Preparative thin layer chromatography eluting with ethyl acetate-hexane = 1:2 afforded ethyl 5-[2-[(benzylamino)methyl]-4-(5-bromo-3-pyridinyl)-7-ethylpyrrolo[l,2-b]pyridazin-3' yl]pentanoate as an yellow gum (19.1 mg). Ethyl 5-[2-[(benzylamino)methyl]-4-(5-bromo-3-pyridinyl)-7-ethy]pyrrolo[l32-b]pyridazin-3-yl]pentanoate NMR (CDC13, 5): 1.23 (3H, t, J=7Hz), 1.30-1 .50 (7H, m), 2.13 (2H, t, J=7Hz), 2.42 (2H, m), 3.03 (2H, q, J=7Hz), 3.96 (4H, m), 4.09 (2H, q, J=7Hz), 5.89 (1H, d, J=5Hz), 6.57 (1H, d, J=5Hz), 7,23-7.42 (5H, m), 7.86 (1H, m), 8.53 (1H, m), 8.77 (lH,m) The following compound was obtained in substantially the same manner as that of Example 271. Example 272 Ethyl 5-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(4-morpholinylmethyl)pyrrolo[ 1,2-b]pyridazin-3-yl]pentanoate NMR (CDC13,5): 1.23 (3H, t, J=7Hz), 1.31-1.56 (7H, m), 2.19 (2H, t, J=7Hz), 2.45- 2.65 (6H, m), 3.02 (2H, q, J=7Hz), 3.60-3.75 (6H, m), 4.09 (2H, q, J-7Hz), 5.88 (1H, d, J=5Hz), 6.57 (1H, d, J=5Hz), 7.89 (1H, m), 8.55 (1H, m), 8.78 (1H, m) Example 273 To a solution of (7-chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazin-3-yl)methanol (40 mg) in N,N-dimethylformarnide (1 mL) was added 40% sodium hydride in oil (5.5 mg) in an ice-water bath. After 20 minutes, to the mixture was added 2-bromoethyl acetate (31 mg) at the temperature. After 15 minutes, the reaction mixture was stirred at ambient temperature for 5 hours. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water three times' and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by p-TLC (hexane-ethyl acetate = 10-1) to give [7-chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazin-3-yl]methyl acetate as a pale yellow solid (42 mg). [7-Chloro-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazin-3-y]]methyl acetate NMR (CDCI3,5): 1.41 (6H, d, J=8Hz), 2.06 (3H, s), 3.21 (1H, m), 4.92 (2H, s), 6.14 (1H, d, J=5Hz), 6.72 (1H, d, J=5Hz), 7.13-7.24 (2H, m), 7.34-7.43 (2H, m) MS(ES1+):m/z361(M+H) The following compound was obtained in substantially the same manner as that of Preparation 20. Example 274 Ethyl {[7-ethyl-4-(4-fluorophenyl)-2-isopropylpyrrolo[l ,2-b]pyridazin-3-yl]methoxy}acetate NMR (CDCI3,5): 1.25 (3H, t, J=8Hz), 130-1.45 (9 H, m), 3.04 (2H, q, J=8Hz), 3.51 (lH,m), 3.97 (2H,s),4J5(2H,q,J=8Hz), 4.40 (2H,s), 6.06 (lH,d,J=5Hz), 6.56 (1H, d, J=5Hz), 7.11-7.22 (2H, m), 7.41-7.51 (2H, m) MS(ESI+):m/z399(M+H) The following compound was obtained in substantially the same manner as that of Preparation 276. Example 275 Ethyl 2-(2-amino-2-oxoethyl)-4-(4-cyanophenyl)-7-ethylpyrrolo[l,2-b]pyridazine-3-carboxylate NMR (CDCI3,5): 0.84 (3H, t, J=7Hz), 1.38 (3H, t, J=7Hz), 3.06 (2H, q, J=7Hz), 3.96 (2H, q, J=7Hz), 4.02 (3H, s), 5.41 (1H, s, br), 6.09 (1H, s, br), 6.28 (1H, d, J=5Hz), 6.75 (1H, d, J=5Hz), 7.53 (2H, d, J=9Hz), 7.77 (2H, d, J=9Hz) MS (ES1+): m/z 753 (2M + H) Example 276 A mixture of 4-(3-cyanophenyl)-7-ethyl-3-(methylsulfonyl)pyrrolo[l ,2-b]pyridazine-2-carboxylic acid (40.0 mg), pyrrolidine (10.8 mg), l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (31.1 mg), and 1-hydroxybenzotriazole (21.9 mg) in N5N-dimethylformamide (1 mL) was stirred for 6 hour at room temperature. The mixture was partitioned between ethyl acetate (20 mL) and IN hydrochloric acid (10 mL). The organic layer was washed with water (10 mL) three times, saturated sodium bicarbonate (10 mL), and brine, dried, and evaporated to give 3-[7-ethyl-3-(methylsulfonyl)-2-(l-pyrrolidinylcarbonyl)pyrrolo[l,2-b]pyridazin-4-yl]benzonitrile as an yellow solid (35.6 mg). 3-[7-Ethyl-3-(methylsulfonyl)-2-(l-pyrrolidiny]carbonyl)pyrrolo[l,2-b]pyridazin-4-yl]benzonitrile NMR (CDCI3, 8): 1.38 (2H, m), 1.99 (4H, m), 3.07 (2H, q, J=7Hz), 3.23 (3H, s), 3.59 (2H, t, J=7Hz), 3.68 (2H, t, J=7Hz), 6.27 (1H, d, J=5Hz), 6.83 (1H, d, J =5Hz), 7.57-7.66 (3H, m), 7.79 (1H, m) MS(ES1+):m/z423(M+H) Example 277 To a solution of 3-[7-ethy]-2-(2-furyl)pyrrolo[l,2-b]pyridazin-4-y]]benzoic acid (40 mg) in N,N-dimethylformamide (4 rnL) was added l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (30 mg), 1-hydroxybenzotriazole (24 mg), and 2-aminoethanol (15 mg) at ambient temperature. After stirring overnight, the reaction mixture was partitioned between ethyl acetate and saturated sodium bicarbonate. The organic layer was washed with water 3 times and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by flash silica gel column chromatography (silica gel, 40 mL) eluted with chloroform-methanol = 50-1 and 20-1 to give an yellow solid (42 mg). The solid was triturated with isopropyl ether to give 3-[7-ethyl-2-(2-furyl)pyrrolo[l,2-b]pyridazin-4-yl]-N-(2-hydroxyethyI)benzamide as an yellow solid (35 mg). 3-[7-Ethyl-2-(2-furyl)pyrrolo[l,2-b]pyridazin-4-yl]-N-(2-hydroxyethyl)benzamide NMR (CDCI3, 5): 1.43 (3H, t, J=8Hz), 239-2.49 (2H, m), 3.10 (2H, q, J=8Hz), 3.60- 3.74 (2H, m), 3.80-3.94 (2H, m), 6.53-6.86 (4H, m), 7.00 (1H, s), 6.61 (1H, d, J=5Hz), 6.72 (1H, d, J=5Hz), 7.03 (1H, br s), 7.07 (1H, d, J=5Hz), 7.55-7.65 (2H, m), 7.86-7.97 (2H, m), 8.17 (1H, br s) MS (ESI+): m/z 376 (M+H) The following compounds were obtained in substantially the same manner as that of Example 283. Example 278 5-[4-(3-Cyanophenyl)-7-ethyI-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]-N-methylpentanamide mp: 60°C NMR (CDC13, 6): 1.02-1.12 (2H5 m), 1.17-1.25 (2H, m), 1.36 (3H, t, J=7Hz), 1.73 (2H, t, J=7Hz), 2.40( 2H, t, J=7Hz), 2.71 (3H, d, J=7Hz), 3.03 (2H, q, J=7Hz), 5.09 (1H, broad s), 5.90 (1H, d, J=4Hz), 6.63 1H, d, J=4Hz), 7.45-7.55 (5H, m), 7.60-7.78 (4H,m) MS: (m/z) 437 (M++H), 115 (bp) Example 279 4-(3-Chlorophenyl)-7-ethyl-3-[5-(4-morpholinyl)-5-oxopentyl]-2-phenylpyrrolo[l,2-b]pyridazine mp: 55-58°C NMR (CDC13,8): 1.05-1.14 (2H, m), 1.17-1.23 (2H, m), 1.35 (3H, t, J=7Hz), 1.84 (2H, t, J=7Hz), 2.45 (2H, t, J=7Hz), 3.02 (2H, q, J=7Hz), 3.24 (2H, t, J=6Hz), 3.50 (2H, I, J=6Hz), 3.55-3.62 (4H, m), 5.99 (1H, d, J=4Hz), 6.62 (1H, d, J=4Hz), 7.30-7.35 (1H, m), 7.40-7.55 (8H, m) MS: (m/z) 502 (M++H), 115 (bp) Example 280 5-[4-(3-ChIorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]-N-methylpentanamide mp: 70-72°C NMR (CDC13, 5): 1.06 (2H, quintet, J=7Hz), 1.22 (2H, quintet, J=7Hz), 1.36 (3H, t, J=7Hz), 1.72 (2H, t, J=7Hz), 2.43 (2H, t, J=7Hz), 2.70 (3H, d, J=7Hz), 3.03 (2H, q, J=7Hz), 5.08 (1H, broad s), 5.99 (1H, d, J=4Hz), 6.61 (1H, d, J=4Hz), 7.29-7.33 (1H, m), 7.41-7.55 (8H, m) MS: (m/z) 446 (M++H), 115 (bp) Example 281 5-[4-(2-Chloro-4-pyridinyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]-N- methylpentanamide NMR (CDC13,8): 1.07 (2H, quintet, J=7Hz), 1.23 (2H, quintet, J=7Hz), 1.36(3H, t, J=7Hz), 1.74 (2H, t, J=7Hz), 2.41 (2H, t, J=7Hz), 2.71 (3H, d, J=7Hz), 3.02 (2H, q, J=7Hz), 5.10 (1H,broad s), 5.95 (1H, d, J=4Hz), 6.64 (1H, d, J=4Hz), 7.31 (1H, d, J=7Hz), 7.42 (1H, s), 7.46-7.52 (1H, m), 7.41-7.55 (1H, d, J=7Hz) MS: (m/z) 447 (M++H), 115 (bp) Example 282 3-{7-Ethyl-3-[5-(4-moipholinyl)-5-oxopenlyl]-2-phenylpyrrolo[l,2-b]pyridazin-4-yljbenzonitrile from 5-[4-(3-cyanophenyl)-7-ethyl-2-phenylpyrrolo[l ,2-b]pyridazin-3-yljpentanoic acid mp: 66-69°C NMR (CDC13, 5): 1.04-1.12 (2H, m), 1.17-1.23 (2H, m), 1.36 (3H, t, J=7Hz), 1.84 (2H, t, J=7Hz), 2.42 (2H, I, J=7Hz), 3.03 (2H, q, J=7Hz), 3.23 (2H, t, J=6Hz), 3.50 (2H, t, J=6Hz), 3.55-3.63 (4H, m), 5.90 (1H, d, J=4Hz), 6.63 (1H, d, J=4Hz), 7.43-7.55 (5H, m), 7.60-7.78 (4H, m) MS: (m/z) 493 (M++H),126 (bp) Example 283 To a solution of 5-[4-(3-cyanophenyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid (50 mg) in N,N-dimethylformamide (1 mL) was added l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (35 mg) and 1-hydroxybenzotriazole (28 mg) at ambient temperature. After 30 minutes, lo the mixture was added morpholine (24 mg). After 5 hours, the reaction mixture was partitioned between ethyl acetate and saturated sodium bicarbonate. The organic layer was washed with water three times and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by flash silica gel column chromatography (silica gel, 40 mL) eluted with hexane-ethyl acetate = 3-1,2-1,1-1,1-3, and 0-1 to give 3-{7-ethyl-2-methyl-3-[5-(4-morpholinyl)-5-oxopentyl]pyrrolo[l52-b]pyridazin-4-yl}benzonitrile as an yellow gum (53 mg). 3-{7-Ethyl-2-methyl-3-[5-(4-moipholinyl)-5-oxopentyl]pyrrolo[l,2-b]pyridazin-4-yl}benzonitrile NMR (CDC13,5): 1.15-1.61 (7H, m), 2.18 (2H, t, J=8Hz), 2.41 (2H, t, J=8Hz)> 2.56 (3H, s), 3.00 (2H, q, J=8Hz), 3.82 (2H, t, J=5Hz), 3.51-3.68 (6H, m), 5.78 (1H, d, J=5Hz), 6.50 (1H, d, J=5Hz), 7.56-7.67 (3H, m), 7.74 (1H, m) MS(ES1+):m/z431(M+H) The following compound was obtained in substantially the same manner as that of Example 283. Example 284 5-4-(3-Cyanophenyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyrida2in-3-yl]pentanamide NMR (CDCI3, 5): 1.31-1.61 (7H, m), 2.11 (2H, t, J=8Hz), 2.40 (2H, 1, J=8Hz), 2.56 (3H, s), 3.00 (2H, q, J=8Hz), 5.36 (2H, br s), 5.79 (1H, d, J=5Hz), 6.50 (1H, d, J=5Hz), 7.56-7.67 (3H, m), 7.75 (1H, m) MS (ESI+): m/z 361 (M+H) Preparation 178 To a suspension of 60% sodium hydride (8.79 g) in tetrahydrofuran (500 mL) was addded cyclohexanol (10 g) and the mixture was stirred at 0 "C for 0.5 hour. To the mixture was added bromoacetic acid (13.9 g) under ice-water cooling and the mixture was heated under reflux for 2 hours. After adding water to the mixture and organic solvent was evaporated in vacuo. The aqueous solution was diluted with water, washed with ether, acidified with 1 N hydrochloric acid, and extracted with ether. The organic layer was separated, dried over magnesium sulfate, and evaporated in vacuo to give (cyclohexyloxy)acetic acid as colorless oil (13.3 g). (cyclohexyloxy)acetic acid 1H NMR (CDCI3) 6 1.18-1.47 (5H,m), 1.52-1.63 (1H, m), 1.72-1.85 (2H, m), 1.90-2.03 (2H, m), 3.36-3.47 (1H, m), 4.13 (2H, s). The following compound(s) was(were) obtained in substantially the same manner as that of Preparation 178. Preparation 179 isopropoxyacetic acid 1H NMR (CDCI3) 5 1.24 (6H, d, J= 7 Hz), 3.68-3.82 (1H, m), 4.11 (2H, s). The following compound(s) was(were) obtained in substantially the same manner as that of Preparation 129 and Preparation 130. Preparation 180 tert-butyl 4-(benzyIoxy)-3-oxobutanoate H NMR (CDCI3) 6 1.44 (9H, s), 3.45 (2H, s), 4.14 (2H, s), 4.60 (2H, s), 7.28-7.40 (5H,m). Preparation 181 tert-butyl 4-(cyclohexyloxy)-3-oxobutanoate H NMR(CDCb) 5 1.18-1.43 (5H,m), 1.47 (9H, s), 1.53-1.63 (lH,m), 1.69-1.85 (2H,m), 1.87-1.97 (2H,m), 3.24-3.38 (lH,m), 3.46 (2H,s), 4.11 (2H,s). Preparation 182 tert-butyl 4-isopropoxy-3-oxobulanoate 1H NMR (CDC13) 6 1.20 (6H, d, J= 7 Hz), 1.47 (9H, s),3.45 (2H, s), 3.60-3.70 (1H, m),4.08(2H,s). The following compound(s) was(were) obtained in substantially the same manner as that of Preparation 159. Preparation 183 1-tert-butyl 4-ethyl 2-acetylsuccinate 1H NMR (CDCI3) 5 1.25 (3H, t, J= 7 Hz), 1.47 (9H, s), 235 (3H, s), 3.08 (2H, m), 3.93 (1H, m), 4.12 (2H, q, J= 7 Hz). Preparation 184 1-tert-butyl 7-ethyl 2-[(benzyloxy)acetyl1Heptanedioate 1H NMR (CDCI3) 6 1.25 (3H, t, J= 7 Hz), 1.30-1.50 (2H, m), 1.40 (9H, s), 1.56-1.72 (2H, m), 1.75-1.95 (2H, m), 2.28 (2H,1, J= 7 Hz), 3.52 (1H, t, J= 7 Hz), 4.11 (2H, q, J= 7 Hz), 4.16 (2H, s), 4.59 (2H, s), 7.27-7.40 (5H, m). Preparation 185 1-tert-butyl 5-ethyI 2-[(benzyloxy)acetyl]pentanedioate 1H NMR (CDCI3) 6 1.25 (3H, t, J= 7 Hz), 1.41 (9H, s), 2.10-2.23 (2H, m), 2.36 (2H, t, J= 7 Hz), 3.66 (1H, t, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 4.18 (2H, s), 4.60 (2H, s), 726-7.38 (5H,m). Preparation 186 1-tert-butyl 7-ethyl 2-[(cyclohexyloxy)acetyl1Heptanedioate 1H NMR (CDCh) 6 1.25 (3H, t, J= 7 Hz), 1.44 (9H, s), 1.15-1.92 (16H,m), 2.29 (2H, t, J= 7 Hz), 3.24-3.38 (1H, m), 3.56 (1H, t, J= 7 Hz), 4.12 (4H, m), Preparation 187 1-tert-butyl 7-ethyl 2-(isopropoxyacetyl)heptanedioate 1H NMR (CDC13) 6 1.20 (6H,d, J= 7 Hz), 1.25 (3H, t, J= 7 Hz), 1.25-1.45 (2H,m), 1.45(9H,s),1.60-1.72(2H5m),1.75-1.95(2H,m),2.29(2H,t,J=7Hz),3.54 (1H, t, J= 7 Hz), 3.60-3.68 (1H, m), 4.11 (2H, s), 4.12 (2H, q, J= 7 Hz). MS(ESl+):m/z345. The following compound(s) was(were) obtained in substantially the same manner as that of Preparation 20. Preparation 188 1-tert-butyl 5-ethyl 2-[(cyclohexyloxy)acetyl]pentanedioate H NMR (CDCI3) 6 1.26 (3H, t, J= 7 Hz), 1.45 (9H,s), 1.18-1.62 (6H,m), 1.66-1.78 (2H, m), 1.84-1.98 (2H, m), 2.10-2.23 (2H, m), 2.38 (2H, t, J= 7 Hz), 3.25-3.38 (1H, m), 3.69 (1H, t, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 4.15 (2H, s). MS(ESI+):m/z357. Preparation 189 To a suspension of 60% sodium hydride (527 mg) in dimethylformamide (20 mL) was added 3,5-pyridinedicarboxylic acid (2.00 g) under ice-water cooling and the mixture was stirred at 0 °C for 1 hour. To the mixture was added (bromomethyl)benzene (2.05 g) and the mixture was stirred at 60 C for 2 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was triturated with ethyl acetate to give 5-[(benzyloxy)carbonyl]nicotinic acid as a pale yellow powder (722 mg). 5-[(benzyloxy)carbonyl]nicotinic acid 1H NMR (DMSO-d6) 6 5.42 (2H, s), 7.34-7.54 (5H, m), 8.63 (1H, m), 9.23-9.34 (2H, m). The following compound(s) was(were) obtained in substantially the same manner as that of Preparation 24. Preparation 190 l-tert-butyl 4-ethy] 2-acetyl-2-[(5-methyl-3-pyridinyl)carbonyl]succinate 1H NMR (CDC1.0 o 1.23 (3H, t, J= 7 Hz), 1.40 (9H, s), 2.38 (3H, s), 2.45 (3H, s), 3.20 (2H, m), 4.13 (2H, q, J= 7 Hz), 7.88 (1H, s), 8.57 (1H, s), 8.74 (1H, s). MS(ESI+):m/z363. Preparation 191 ethyl 2-[(5-methyl-3-pyridinyl)carbonyl]-3-oxobutanoate 1H NMR (CDC13) 6 0.96 (3H, t, J= 7 Hz), 2.15 (3H, s), 2.45 (3H, s), 4.03 (2H, q, J= 7 Hz), 4.12 (1H, t, J= 7 Hz), 7.89 (1H, s), 8.54 (1H, s), 8.72 (1H, s). MS (ES1+): m/z 250. Preparation 192 l-tert-butyl 6-ethyl 2-acetyl-2-[(5-bromo-3-pyridinyl)carbonyl1Hexanedioate 1H NMR (CDCI3) 5 1.25 (3H, t, J= 7 Hz), 1.36 (9H, s), 1.60-1.73(2H, m), 2.23-2.35 (2H, m), 2.38 (2H, t, J= 7 Hz), 2.48 (3H, s), 4.12 (2H, q, J= 7 Hz), 8.20 (1H, m), 8.78 (lH,m), 8.81 (lH,m). Preparation 193 l-tert-butyl 5-ethyl 2-[(5-bromo-3-pyridinyl)carbonyl]-2-(methoxyacetyl)pentanedioate 1H NMR (CDCI3) 6 1-25 (3H, t, J= 7 Hz), 1.39 (9H, s), 2.40-2.47 (2H, m), 2.55-2.67 (2H, m), 3.36 (3H, s), 4.12 (2H, q, J= 7 Hz), 4.27 (1H, d, J= 17 Hz), 4.40 (1H, d, J= 17 Hz), 8.21 (1H, m), 8.79 (1H, d, J= 2 Hz), 8.82 (1H, d, J= 2 Hz). MS (ESI+): m/z 472 474. Preparation 194 l-tert-butyl 7-ethyl 2-acetyl-2-({5-[(benzyloxy)carbonylj-3- pyridinyl}carbonyl)heptanedioate 1H NMR (CDCI3) 5 1.23 (3H, t, J= 7 Hz), 1.20-1.40 (2H, m), 1.32 (9H, s), 1.65-1.76 (2H, m), 2.19-2.26 (2H, m), 2.32 (2H, t, J= 7 Hz), 2.44 (3H, s), 4.12 (2H, q, J= 7 Hz), 5.41 (2H, s), 7.35-7.48 (5H, m), 8.62 (1H, m), 9.07 (1H, d, J= 2 Hz), 9.33 (lH,d,J=2Hz). MS (ES1+): m/z 526. Preparation 195 1-tert-bulyl 7-ethyl 2-[(benzyloxy)acetyl]-2-[(5-methyl-3- pyridinyl)carbonyl1Heptanedioate 1H NMR (CDCI3) 6 1.23 (3H, t, J= 7 Hz), 1.20-1.46 (2H, m), 1.32 (9H, s), 1.60-1.74 (2H, m), 2.10-2.36 (4H, m), 2.35 (3H, s), 4.10 (2H, q, J= 7 Hz), 4.38 (1H, d, J= 18 Hz), 4.53 (1H, d, J= 18 Hz), 4.54 (2H, m), 7.27-7.40 (5H, m), 7.79 (1H, m), 8.54 (1H, d, J= 2 Hz), 8.72 (1H, d, J= 2 Hz). MS(ES1+):m/z512. Preparation 196 1-tert-butyl 5-ethyl 2-[(benzyloxy)acetyl]-2-[(5-methyl-3- pyridinyl)carbonyl]pentanedioate 1H NMR (CDCI3) 6 1.26 (3H, t, J= 7 Hz), 1.34 (9H, s), 2.35 (3H, s), 2.40-2.72 (4H, m), 4.12 (2H, q, J= 7 Hz), 4.38 (1H, d, J= 17 Hz), 4.50 (1H, d, J= 17 Hz), 4.53 (2H, m), 7.25-7.38 (5H, m), 7.81 (1H, s), 8.54 (1H, s), 8.73 (1H, s). MS (ESI+): m/z 484. Preparation 197 1-tert-butyl 7-ethyl 2-[(cyclohexyloxy)acetyl]-2-[(5-methyl-3- pyridinyl)carbonyl1Heptanedioate 1H NMR (CDCI3) 5 1.25 (3H, t, J= 7 Hz), 1.16-1.55 (10H, m), 1.37 (9H, s), 1.60-1.76 (2H, m), 1.78-1.90 (2H, m), 2.15-2.28 (2H, m), 2.31 (2H, t, J= 7 Hz), 2.39 (3H, s), 3.17-3.29 (1H, m), 4.12 (2H, q, J= 7 Hz), 4.34 (1H, d, J= 18 Hz), 4.44 (1H, d, J= 18 Hz), 7.86 (1H, s), 8.56 (1H, s), 8.76 (1H, s). MS (ES1+): m/z 504. Preparation 198 1-tert-butyl 7-ethyl 2-[(5-bromo-3-pyridinyl)carbonyl]-2- [(cyclohexyloxy)acetyl1Heptanedioate 1H NMR (CDCI3) 6 1.24 (3H, t, J= 7 Hz), 1.39 (9H, s), 1.16-1.88 (14H, m), 2.15-2.40 (4H, m), 3.16-3.28 (1H, m), 4.10 (2H, q, J= 7 Hz), 4.28 (1H, d, J= 18 Hz), 4.38 (1H, d,J= 18 Hz), 8.20 (1H, m), 8.78 (1H, d, J= 2 Hz), 8.84 (1H, d, J= 2 Hz). MS (ESI+): m/z 568 570. Preparation 199 1-tert-butyl 5-ethyl 2-[(cyc]ohexyloxy)acetyl]-2-[(5-methyl-3- pyridinyl)carbony]]pentanedioate !H NMR (CDC13) 6 1 -24 (3H, t, J= 7 Hz), 1.15-1.38 (4H, m), 1.39 (9H, s), 1.45-1.75 (4H, m), 1.76-1.93 (2H, m), 2.39 (3H, s), 2.45-2.75 (4H, m), 3.17-3.30 (1H, m), 4.12 (2H, q, J= 7 Hz), 4.32 (1H, d, J= 17 Hz), 4.41 (1H, d, J= 17 Hz), 7.88 (1H, s), 8.55 (lH,s), 8.77 (lH,s). MS (ESI+): m/z 476. Preparation 200 1-tert-butyl 5-ethyl 2-[(5-bromo-3-pyridinyl)carbonyl]-2- [(cyclohexyloxy)acetyl]pentanedioate 1H NMR (CDCI3) 6 1.26 (3H, t, J= 7 Hz), 1.15-1.35 (4H, m), 1.40 (9H, s), 1.40-1.65 (2H, m), 1.65-1.75 (2H, m), 1.75-1.92 (2H, m), 2.35-2.85 (4H, m), 3.16-3.32 (1H, m), 4.12 (2H, q, J= 7 Hz), 4.28 (1H, d, J= 17 Hz), 4.35 (1H, d, J= 17 Hz), 8.22 (1H, t, J= 2 Hz), 8.78 (1H, d, J= 2 Hz), 8.87 (1H, d, J= 2 Hz). MS (ES1+): m/z 540 542. Preparation 201 1-tert-butyl 7-ethyl 2-(isopropoxyacetyl)-2-[(5-methyl-3- pyridinyl)carbonyl1Heptanedioate 1H NMR (CDCI3) 6 1.12 (6H, d, J= 7 Hz), 1.23 (3H, t, J= 7 Hz), 1.30-1.55 (2H, m), 1.37 (9H, s), 1.63-1.77 (2H, m), 2.19-2.28 (2H, m), 2.28 (2H, t, J= 7 Hz), 2.39 (3H, s), 3.53-3.64 (1H, m), 4.10 (2H, q, J= 7 Hz), 4.31 (1H, d, J= 18 Hz), 4.42 (1H, d, J= 18 Hz), 7.86 (1H, s), 8.55 (1H, s), 8.74 (1H, s). MS (ESI+): m/z 464. Preparation 202 1-tert-butyl 7-ethyl 2-[(5-bromo-3-pyridinyl)carbonyl]-2-(isopropoxyacetyl)heptanedioate 1H NMR (CDCI3) 5 1.10 (6H, d, J= 7 Hz), 1.24 (3H, t, J= 7 Hz), 1.39 (9H, s), 1.18-1.48 (2H, m), 1.64-1.77 (2H, m), 2.18-2.37 (4H, m), 3.52-3.64 (1H, m), 4.12 (2H, q, J= 7 Hz), 4.25 (1H, d, J= 17 Hz), 4.36 (1H, d, J= 17 Hz), 8.19 (1H, t, J= 2 Hz), 8.77 (1H, d, J= 2 Hz), 8.83 (1H, d, J= 2 Hz). MS (ESI+): m/z 528 530. Reparation 203 l-tcrt-butyl 7-ethyl 2-[(acetyloxy)acelyl]-2-[(5-methyl-3- :>yridinyl)carbonyl1Heptanedioale 1H NMR (CDC13) 6 1.24 (3H, t, J= 7 Hz), 1.33 (9H, s), 1.20-1.42 (2H, m), 1.63-1.74 (2H, m), 2.14 (3H, s), 2.27-2.38 (4H, m), 2.40 (3H, s), 4.10 (2H, q, J= 7 Hz), 5.08 (1H, d, J= 18 Hz), 5.36 (1H, d, J= 18 Hz), 7.84 (1H, s), 8.56 (1H, s), 8.75 (1H, s). MS (ES1+): m/z 464. The following compound(s) was(were) obtained in substantially the same manner as that of Preparation 78. Preparation 204 ethyl 3-[(5-methyl-3-pyridinyl)carbonyl]-4-oxopentanoate 1H NMR (CDCI3) 6 1.23 (3H, t, J= 7 Hz), 2.21 (3H, s), 2.44 (3H, s), 3.03 (2H, t, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 4.96 (1H, t, J= 7 Hz), 8.08 (1H, s), 8.66 (1H, s), 9.03 (lH,s). MS (ES1+): m/z 264. Preparation 205 ethyl 5-[(5-bromo-3-pyridinyl)carbonyl]-6-oxoheptanoate 1H NMR (CDCI3) 5 1.25 (3H, t, J= 7 Hz), 1.60-1.78 (2H,m), 1.98-2.12 (2H, m), 2.20 (3H, s), 2.36 (2H, t, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 4.39 (1H, t, J= 7 Hz), 8.38 (1H, m), 8.87 (1H, d, J= 2 Hz), 9.08 (1H, d, J= 2 Hz). Preparation 206 ethyl 4-[(5-bromo-3-pyridinyl)carbonyl]-6-methoxy-5-oxohexanoate 1H NMR (CDCI3) 5 1.25 (3H, t, J= 7 Hz), 2.04-2.16 (1H, m), 2.20-2.34 (1H, m), 2.40-2.48 (2H, m), 3.22 (3H, s), 3.93 (1H, d, J= 17 Hz), 4.00 (1H, d, J= 17 Hz), 4.12 (2H, q, J= 7 Hz), 4.85 (1H, m), 8.47 (1H, m), 8.88 (1H, s), 9.16 (1H, s). MS(ESI+):m/z372 374. Preparation 207 benzyl 5-(2-acetyl-7-ethoxy-7-oxoheplanoyl)nicotinate 1H NMR (CDCI3) 6 1.24 (3H, t, J= 7 Hz), 1.30-1.43 (2H, m), 1.65-1.75 (2H, m), 1.93-2.15 (2H, m), 2.19 (3H, s), 2.29 (2H, t, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 4.44 (1H, t, J= 7 Hz), 5.43 (2H, s), 7.35-7.50 (5H, m), 8.81 (1H, m), 9.28 (1H, d, J= 2 Hz),9.39(lH,d,J=2Hz). MS (ESI+): m/z 426. Preparation 208 ethyl 8-(benzyloxy)-6-[(5-methyl-3-pyridinyl)carbonyl]-7-oxooctanoate 1H NMR (CDCI3) 6 1.22 (3H, t, J= 7 Hz), 1.30-1.43 (2H, m), 1.60-1.69 (2H, m), 1.73-1.86 (1H, m), 1.95-2.08 (1H, m), 2.25 (2H, t, J= 7 Hz), 2.34 (3H, s), 4.05 (2H, s), 4.07 (2H, q, J= 7 Hz), 4.35-4.45 (2H, m), 4.69 (1H, t, J= 7 Hz), 7.09 (2H, m), 7.17-7.25 (3H, m), 7.93 (1H, s), 8.58 (1H, d, J= 2 Hz), 8.94 (1H, d, J= 2 Hz). MS (ESI+): m/z 412. Preparation 209 ethyl 6-(benzyloxy)-4-[(5-methyl-3-pyridinyl)carbonyl]-5-oxohexanoate 1H NMR (CDCI3) 5 1.23 (3H, t, J= 7 Hz), 2.07-2.35 (2H, m), 2.34 (3H, s), 2.38-2.48 (2H, m), 4.05 (2H, s), 4.12 (2H, q, J= 7 Hz), 4.34 (1H, d, J= 17 Hz), 4.41 (1H, d, J= 17 Hz), 4.90 (1H, m), 7.03 (2H, m), 7.15-7.25 (3H, m), 8.00 (1H, s), 8.57 (1H, s),9.02(lH,s). MS (ESI+): m/z 384. Preparation 210 ethyl 8-(cyclohexyloxy)-6-[(5-methyl-3-pyridinyl)carbonyl]-7-oxooctanoate 1H NMR (CDCI3) 5 0.91-1.70 (12H, m), 1.23 (3H, t, J= 7 Hz), 1.70-1.85 (2H, m), 1.96-2.04 (2H, m), 2.27 (2H, t, J= 7 Hz), 2.43 (3H, s), 3.14-3.28 (1H, m), 4.00 (2H, s), 4.12 (2H, q, J= 7 Hz), 4.76 (1H, t, J= 7 Hz), 8.04 (1H, s), 8.62 (1H, s), 9.00 (1H, s). MS (ES1+): m/z 404. Preparation 211 ethyl 6-[(5-bromo-3-pyridinyl)carbony]]-8-(cyclohexyloxy)-7-oxooctanoate 1H NMR (CDC13) 6 0.95-1.87 (14H, m), 1.23 (3H, t, J= 7 Hz), 1 .96-2.07 (2H, m), 2.28 (2H, t, J= 7 Hz), 3.16-3.27 (1H, m), 3.96-4.07 (2H, m), 4.12 (2H, q, J= 7 Hz), 4.72 (1H, t, J= 7 Hz), 8.38 (1H, m), 8.87 (1H, d, J= 2 Hz), 9.08 (1H, d, J= 2 Hz). MS (ES1+): m/z 468 470. Preparation 212 ethyl 6-(cyclohexyloxy)-4-[(5-methyl-3-pyridinyl)carbonyl]-5-oxohexanoate 1H NMR (CDC13) 6 0.88-1.25 (5H, m), 1.24 (3H, t, J= 7 Hz), 1.40-1.83 (5H, m), 2.04-2.14 (1H, m), 2.18-2.34 (1H, m), 2.42 (2H, m), 2.44 (3H, s), 3.13-3.27 (1H, m), 4.00 (2H, s), 4.12 (2H, q, J= 7 Hz), 4.93 (1H, m), 8.13 (1H, s), 8.63 (1H, d, J= 2Hz),9.07(lH,d,J=2Hz). MS (ESI+): m/z 376. Preparation 213 ethyl 4-[(5-bromo-3-pyridinyl)carbonyl]-6-(cyclohexyloxy)-5-oxohexanoate 1H NMR (CDCI3) 8 0.88-1.85 (10H, m), 1.25 (3H, t, J= 7 Hz), 2.02-2.14 (1H, m), 2.18-2.34 (1H, m), 2.40-2.50 (2H, m), 3.15-3.27 (1H, m), 3.97 (1H, d, J= 17 Hz), 4.02 (1H, d, J= 17 Hz), 4.13 (2H, q, J= 7 Hz), 4.87-4.95 (1H, m), 8.48 (1H, t, J= 2 Hz), 8.88 (1H, d, J= 2 Hz), 9.19 (1H, d, J= 2 Hz). MS (ES1+): m/z 440 442. Preparation 214 ethyl 8-isopropoxy-6-[(5-methyl-3-pyridinyl)carbonyl]-7-oxooctanoate :H NMR (CDCI3) 6 0.86 (3H, d, J= 7 Hz), 1.02 (3H, d, J= 7 Hz), 1.23 (3H, t, J= 7 Hz), 1.30-1.48 (2H, m), 1.60-1.72 (2H, m), 1.72-1.88 (1H, m), 1.95-2.07 (1H, m), 2.27 (2H, t, J= 7 Hz), 2.43 (3H, s), 3.44-3.54 (1H, m), 3.95 (1H, d, J= 18 Hz), 4.03 (1H, d, J= 18 Hz), 4.08 (2H, q, J= 7 Hz), 4.73 (1H, t, J= 7 Hz), 8.06 (1H, s), 8.63 (lH,s), 9.02 (lH,s). MS (ES1+): m/z 364. Preparation 215 ethyl 6-[(5-bromo-3-pyridiny])carbonyl]-8-isopropoxy-7-oxooctanoate 1H NMR (CDCI3) 5 0.88 (3H, d, J= 7 Hz), 1.03 (3H, t, J= 7 Hz), 1.23 (3H, t, J= 7 Hz), 1.20-1.46 (2H, m), 1.58-1.72 (2H, m), 1.73-1.87 (1H, m), 1.95-2.07 (1H, m),2.27 (2H, 1, J= 7 Hz), 3.46-3.58 (1H, m), 3.94 (1H, d, J= 17 Hz), 4.03 (1H, d, J= 17 Hz), 4.10 (2H, q, J= 7 Hz), 4.68 (1H, t, J= 7 Hz), 8.40 (1H, t, J= 2 Hz), 8.86 (1H, d, J= 2 Hz), 9.08 (1H, d, J= 2 Hz). MS(ESl+):m/z428 430. Preparation 216 ethyl 8-(acetyloxy)-6-[(5-methyl-3-pyridinyl)carbonyl]-7-oxooctanoate 1H NMR (CDCI3) 8 1.24 (3H, t, J= 7 Hz), 1.37-1.47 (2H, m), 1.60-1.77 (2H, m), 2.01 (3H, s), 1.97-2.08 (2H, m), 2.29 (2H, t, J= 7 Hz), 2.44 (3H, s), 4.10 (2H, q, J= 7 Hz), 4.52 (1H, t, J= 7 Hz), 4.68 (1H, d, J= 18 Hz), 4.76 (1H, d, J= 18 Hz), 8.04 (1H, s), 8.66 (1H, s), 8.98 (1H, s). MS(ESI+):m/z364. The following compound(s) was(were) obtained in substantially the same manner as that of Example 21. Example 285 ethyl [7-ethyl-2-methyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]acetate 1H NMR (CDCI3) 6 1.24 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 2.40 (3H, s), 2.50 (3H, s), 3.02 (2H, q, J= 7 Hz), 3.44 (2H, s), 4.14 (2H, q, J= 7 Hz), 5.98 (1H, d, J= 4 Hz), 6.56 (1H, d, J= 4 Hz), 7.55 (1H, s), 8.45 (1H, s), 8.54 (1H, s). MS (ES1+): m/z 338. Example 286 ethyl 7-ethyl-2-methyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazine-3-carboxylate 1H NMR (CDCh) 6 0.96 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 2.41 (3H, s), 2.61 (3H, s), 3.04 (2H, q, J= 7 Hz), 4.05 (2H, q, J= 7 Hz), 6.30 (1H, d, J= 4 Hz), 6.67 (1H, d, J= 4 Hz), 7.58 (1H, s), 8.48 (1H, d, J= 2 Hz), 8.51 (1H, d, J= 2 Hz). MS (ES1+): m/z 324. Example 287 ethyl 4-[4-(5-bromo-3-pyrJdinyl)-7-ethyl-2-methylpyno]o[l,2-b]pyridazin-3-yl]butanoate !H NMR (CDCI.0 6 1.21 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.67-1.78 (2H, m), 2.22 (2H, t, J= 7 Hz), 2.42-2.54 (2H, m), 2.59 (3H, s), 3.01 (2H, q, J= 7 Hz), 4.06 (2H, q, J= 7 Hz), 5.87 (1H, d, J= 4 Hz), 6.53 (1H, d, J= 4 Hz), 7.87 (1H, m), 8.54 (1H, d, J= 2 Hz), 8.77 (1H, d, J= 2 Hz). MS (ES1+): m/z 430 432. Example 288 ethyl 3-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3- yljpropanoate 1H NMR (CDCI3) 5 1.20 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 2.42 (2H, t, J= 7 Hz), 2.85-2.97 (2H, m), 3.06 (2H, q, J= 7 Hz), 3.46 (3H, s), 4.08 (2H, q, J= 7 Hz), 4.65 (2H, s), 5.94 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.87 (1H, m), 8.54 (1H, d, J=2Hz),8.78(lH,d,J=2Hz). MS (ES1+): m/z 446 448. Example 289 ethyl 4-[2-[(acetyloxy)methyl]-4-(5-bromo-3-pyridinyl)-7-ethylpyrrolo[l,2-b]pyridazin-3- yljbutanoate -U NMR (CDCI3) 6 1.20 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.60-1.75 (2H, m), 2.17 (3H, s), 2.10-2.28 (2H, m), 2.45-2.60 (2H, m), 3.02 (2H, q, J= 7 Hz), 4.05 (2H, q, J= 7 Hz), 5.32 (2H, s), 5.95 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.88 (1H, m), 8.55 (1H, m), 8.78 (1H, m). MS (ES1+): m/z 488 490. Example 290 benzyl 5-[3-(5-ethoxy-5-oxopentyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-4- yl]nicotinate 1H NMR (CDCb) 6 1.24 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.33-1.60 (4H, m), 2.18 (2H, t, J= 7 Hz), 2.35-2.47 (2H, m), 2.56 (3H, s), 3.03 (2H, q, J= 7 Hz), 4.10 (2H, q, J= 7 Hz), 5.42 (2H, s), 5.82 (1H, d, J= 4 Hz), 6.53 (1H, d, J= 4 Hz), 7.36- 7.47 (5H, m), 8.33 (1H, m), 8.77 (1H, d, J= 2 Hz), 9.33 (1H, d, J= 2 Hz). MS (ES1+): m/z 500. Example 293 ethyl 5-[2-[(benzyloxy)methyl]-7-elhyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridaziiv 3-yl]pentanoate !H NMR (CDCI3) 5 1.22 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 1.20-1.50 (4H, m), 2.06 (2H, t, J= 7 Hz), 2.42 (3H, s), 2.47-2.63 (2H, m), 3.05 (2H, q, J= 7 Hz), 4.0s (2H, q, J= 7 Hz), 4.64 (2H, s), 4.73 (2H, s), 5.90 (1H, d, J= 4 Hz), 6.58 (1H, d, J 4 Hz), 7.27-7.39 (5H, m), 751 (1H, s), 8.41 (1H, d, J= 2 Hz), 8.53 (1H, d, J= 2 Hz). Example 292 ethyl 3-[2-[(benzyloxy)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyiidazJD 3-yl]propanoate 1H NMR (CDCI3) 6 1.16 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 2.36 (2H, t, J= 7 IV,. 2.42 (3H, s), 2.80-3.00 (2H, m), 3.06 (2H, q, J= 7 Hz), 4.03 (2H, q, J= 7 Hz), i (-(2H, s), 4.75 (2H, s), 5.92 (1H, d, J= 2 Hz), 6.59 (1H, d, J= 2 Hz), 7.26-7.38 (ML m), 7.48 (1H, s), 8.40 (1H, d, J= 2 Hz), 8.53 (1H, d, J= 2 Hz). MS (ES1+): m/z 458. Example 293 ethyl 5-[2-[(cyclohexyloxy)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2- b]pyridazin-3-yl]pentanoate 1H NMR (CDCI3) 5 1.20-1.60 (10H, m), 1.25 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 I b 1 1.70-1.83 (2H, m), 1.96-2.07 (2H, m), 2.15 (2H, t, J= 7 Hz), 2.43 (3H, s), 2.5. 2.68 (2H, m), 3.04 (2H, q, J= 7 Hz), 3.42-3.53 (1H, m), 4.08 (2H, q, J= 7 11/) 4.68 (2H, s), 5.88 (1H, d, J= 4 Hz), 6.55 (1H, d, J= 4 Hz), 7.53 (1H, s), 8.42 Example 294 ethyl 5-{4-(5-bromo-3-pyridinyl)-2-[(cyclohexyloxy)methyl]-7-ethylpyrrolo[l,2- b]pyridazin-3-yl}pentanoate 1HNMR (CDCI3) 6 1.22-1.62 (10H, m), 1.23 (3H, I, J= 7 Hz), 1.37 (3H, t, J = 11/). 1.73-1.86 (2H,m), 1.98-2.07 (2H,m),2.18 (2H,1, J= 7 Hz),2.53-2.70 (211 mi. 3.03 (2H, q, J= 7 Hz), 3.42-3.56 (1H, m), 4.12 (2H, q, J= 7 Hz), 4.69 (2H, s), 5.88 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.88 (1H, m), 8.54 (1H, d, J= 2 Hz), 8.77 (lH,dJ=2Hz). Example 295 :thyl 3-[2-[(cyclohexyloxy)methyi]-7-ethyl-4-(5-methyl-3-pyridiny])pyrrolo[l,2- )]pyridazin-3-yl]propanoate 1H NMR (CDC13) 6 1.19 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.16-1.45 (4H, m), 1.52-1.65 (2H, m), 1.73-1.83 (2H, m), 1.98-2.07 (2H, m), 2.35-2.47 (2H, m), 2.42 (3H, s), 2.84-2.98 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.45-3.56 (1H, m), 4.06 (2H, q, J= 7 Hz), 4.71 (2H, s), 5.89 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.50 (1H, s), 8.42 (lH,s), 8.53 (lH,s). MS (ES1+): m/z 450. Example 296 ethyl 3-{4-(5-bromo-3-pyridinyl)-2-[(cyclohexyloxy)methyl]-7-ethylpyrrolo[l,2- b]pyridazin-3-yl}propanoate 1H NMR (CDCI3) 5 1.20 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.15-1.60 (6H, m), 1.73-1.85 (2H, m), 1.97-2.08 (2H, m), 2.45 (2H, t, J= 7 Hz), 2.83-2.97 (2H, m), 3.05 (2H, q, J= 7 Hz), 3.42-3.56 (1H, m), 4.08 (2H, q, J= 7 Hz), 4.71 (2H, s), 5.90 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.86 (1H, t, J= 2 Hz), 8.53 (1H, d, J= 2 Hz),8.77(lH,d,J=2Hz). MS(ESl+):m/z514 516. Example 297 ethyl 5-[7-ethyl-2-(isopropoxymethyl)-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin- 3-yl]pentanoate 1H NMR (CDCI3) 6 1.23 (3H, t, J= 7 Hz), 1.26 (6H, d, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.38-1.62 (4H, m), 2.17 (2H, t, J= 7 Hz), 2.43 (3H, s), 2.53-2.68 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.76-3.88 (1H, m), 4.08 (2H, q, J= 7 Hz), 4.66 (2H, s), 5.88 (1H, d, J= 4 Hz), 6.57 (1H, d, J= 4 Hz), 7.52 (1H, s), 8.42 (1H, s), 8.53 (1H, s). MS(ESI+):m/z438. Example 298 ethyl 5-[4-(5-bromo-3-pyndinyl)-7-ethyl-2-(isopropoxymethyl)pyirolo[l,2-b]pyridazin-3- y]]pentanoate H NMR (CDCI3) 0 1.23 (3H, i, J= 7 Hz), 1.25 (6H, d, J= 7 Hz), 1.37 (3H, t, .1= 7 Hz), 1.37-1.64 (4H, m), 2.15 (2H, t, J= 7 Hz), 2.54-2.72 (2H, m), 3.02 (2H, q, J= 7 Hz), 3.75-3.87 (1H, m), 4.09 (2H, q, J= 7 Hz), 4.66 (2H, s), 5.89 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.88 (1H, m), 8.55 (1H, d, J= 2 Hz), 8.78 (1H, d, J= 2 Hz). MS (ESI+): m/z 502 504. Example 299 ethyl 5-[2-[(acetyloxy)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin- 3-yl]pentanoate H NMR (CDCb) 6 1.23 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.30-1.58 (4H, m), 2.13 (2H, t, J= 7 Hz), 2.18 (3H, s), 2.44 (3H, s), 2.40-2.55 (2H, m), 3.02 (2H, q, J= 7 Hz), 4.08 (2H, q, J= 7 Hz), 5.29 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.52 (1H, s), 8.42 (1H, s), 8.53 (1H, s). MS (ESI+): m/z 438. The following compound(s) was(were) obtained in substantially the same manner as that of Example 236. Example 300 ethyl 4-{4-[5-(l-ethoxyvinyl)-3-pyridinyl]-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3- yljbutanoate TH NMR (CDCI3) 5 1.24 (3H, t, J= 7 Hz), 1.38 (3H51, J= 7 Hz), 1.41 (3H, t, J= 7 Hz), 1.68-1.80 (2H, m), 2.22 (2H, t, J= 7 Hz), 2.44-2.54 (2H, m), 2.59 (3H, s), 3.03 (2H, q, J= 7 Hz), 3.95 (2H, q, J= 7 Hz), 4.10 (2H, q, J= 7 Hz), 4.36 (1H, d, J= 3 Hz), 4.77 (1H, d, J= 3 Hz), 5.88 (1H,d, J= 4 Hz), 6.52 (1H, d, J= 4 Hz), 7.92 (1H, m), 8.53 (1H, d, J= 2 Hz), 8.93 (1H, d, J= 2 Hz). MS (ESI+): m/z 422. Example 301 ethyl 3-[4-[5-(l -ethoxyvinyl)-3-pyridinyl]-7-ethyl-2-(methoxymethyl)pyrrolo[l ,2- b]pyridazin-3-yl]propanoate 1H NMR (CDCI3) 6 1.19 (3H, t, J= 7 Hz), 1.26 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 2.42 (2H, t, J= 7 Hz), 2.84-2.97 (2H, m), 3.07 (2H, q, J= 7 Hz), 3.47 (3H, s), 3.97 (2H, q, J= 7 Hz), 4.08 (2H, q, J= 7 Hz), 4.36 (1H, d, J= 3 Hz), 4.66 (2H, s), 4.77 (1H, d, J= 3 Hz), 5.95 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.92 (1H, m), 8.54 (1H, d, J= 2 Hz), 8.95 (1H, d, J= 2 Hz). MS(ESl+):m/z438. Example 302 ethyl 3-[7-elhyl-2-(methoxymethyl)-4-(5-vinyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3- yl]propanoate 1H NMR (CDCI3) 6 1.18 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 2.40 (2H, t, J= 7 Hz), 2.84-2.98 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.47 (3H, s), 4.04 (2H, q, J= 7 Hz), 4.65 (2H, s), 5.46 (1H, d, J= 11 Hz), 5.87 (1H, d, J= 18 Hz), 5.94 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 6.72-6.83 (1H, dd, J= 11 Hz, 18 Hz), 7.74 (1H, m), 8.49 (1H, d, J= 2 Hz), 8.72 (1H, d, J= 2 Hz). MS(ESI+):m/z394. Example 303 methyl 4-[7-ethyl-2-(methoxymethyl)-4-(5-vinyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3- yl]butanoate 1H NMR (CDCI3) 6 1.38 (3H, t, J= 7 Hz), 1.65-1.78 (2H, m), 2.23 (2H, t, J= 7 Hz), 2.54-2.70 (2H, m), 3.05 (2H, q, J= 7 Hz), 3.47 (3H, s), 3.58 (3H, s), 4.67 (2H, s), 5.46 (1H, d, J= 11 Hz), 5.88 (1H, d, J= 18 Hz), 5.93 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 6.73-6.83 (1H, dd, J= 11 Hz, 18 Hz), 7.77 (1H, m), 8.51 (1H, d, J= 2 Hz),8.71(lH,d,J=2Hz). MS (ESI+): m/z 394. Example 304 methyl 4-[4-[5-(l-ethoxyvinyl)-3-pyridinyl]-7-ethyl-2-(methoxymethyl)pyrrolo[l,2- b]pyridazin-3-yl]butanoate 1H NMR (CDCI3) 6 1.26 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 1.67-1.82 (2H, m), 2.22 (2H, t, J= 7 Hz), 2.53-2.67 (2H, m), 3.04 (2H, q, J= 7 Hz), 3.47 (3H, s), 3.58 (3H, s), 3.95 (2H, q, J= 7 Hz), 4.34 (1H, d, J= 2 Hz), 4.67 (2H, s), 4.77 (1H, d, J= 2 Hz), 5.93 (1H, d, J= 4 Hz), 6.59 (1H, d, J= 4 Hz), 7.92 (1H, m), 8.54 (1H, d, J= 2Hz),8.95(lH,d,J=2Hz). MS (ES1+): m/z 438. xample 305 Ihyl 3-{4-[5-(l-eth°xyvinyl)-3-pyridinyl]-7-ethyI-2-methylpyrrolo[l,2-b]pyridazin-3- l}propanoate 1H NMR (CDC13) 6 1.19 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 1.44 (3H, t, J= 7 Hz), 2.33-2.43 (2H, m), 2.58 (3H, s), 2.76-2.87 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.96 (2H, q, J= 7 Hz), 4.06 (2H, q, J= 7 Hz), 4.36 (1H, d', J= 2 Hz), 4.77 (1H, d, J= 2 Hz), 5.91 (1H, d, J= 4 Hz), 6.54 (1H, d, J= 4-Hz), 7.91 (1H, m), 8.53 (1H, d, J= 2 Hz),8.96(lH,d,J=2Hz). MS (ES1+): m/z 408. The following compound(s) was(were) obtained in substantially the same manner as that of Example 251. Example 306 ethyl 4-[4-(5-acetyl-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]butanoate 5H NMR (CDCI3) 6 1.19 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 1.66-1.82 (2H, m), 2.21 (2H, t, J= 7 Hz), 2.41-2.51 (2H, m), 2.60 (3H, s), 2.69 (3H, s), 3.03 (2H, q, J= 7 Hz), 4.03 (2H, q, J= 7 Hz), 5.83 (1H, d, i= 4 Hz), 6.53 (1H, d, J= 4 Hz), 8.25 (1H, m), 8.79 (1H, d, J= 2 Hz), 9.25 (1H, d, J= 2 Hz). MS (ES1+): m/z 394. Example 307 ethyl 3-[4-(5-acetyl-3-pyridinyl)-7-ethyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3- yljpropanoate 1H NMR (CDCI3) 6 1.18 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 2.41 (2H, t, J= 7 Hz), 2.70 (3H, s), 2.83-2.96 (2H, m), 3.06 (2H, q, J= 7 Hz), 3.47 (3H, s), 4.03 (2H, q, J= 7 Hz), 4.66 (2H, s), 5.88 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 8.26 (1H, m), 8.79 (1H, d, J= 2 Hz), 9.25 (1H, d, J= 2 Hz). Example 308 methyl 4-[4-(5-acetyl-3-pyncliny])-7-elhy]-2-(methoxymethyl)pyrro]o[l,2-b]pyridazin-3-y]]butanoate 1H NMR (CDC13) 6 1 .38 (3H, t, J= 7 Hz), 1.64-1.80 (2H, m), 2.20 (2H, t, J= 7 Hz), 2.53-2.65 (2H, m), 2.70 (3H, s), 3.05 (2H, q, J= 7 Hz), 3.47 (3H, s), 3.57 (3H, s), 4.67 (2H, s), 5.87 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 8.27 (1H, s), 8.81 (1H, d, J= 2 Hz), 9.26 (1H, d, J= 2 Hz). MS (ESI+): m/z 410. Example 309 ethyl 3-[4-(5-acetyl-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3- yl]propanoate 1H NMR (CDC13) 8 1.19 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 2.33-2.42 (2H, m), 2.59 (3H, s), 2.69 (3H, s), 2.75-2.83 (2H, m), 3.02 (2H, q, J= 7 Hz), 4.05 (2H, q, J= 7 Hz), 5.83 (1H, d, J= 4 Hz), 6.53 (1H, d, J= 4 Hz), 8.25 (1H, m), 8.78 (1H, d, J= 2 Hz), 9.26 (1H, d, J= 2 Hz). MS (ESI+): m/z 380. Example 310 A mixture of benzyl 5-[3-(5-ethoxy-5-oxopentyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-4-yl]nicotinate (330 mg) and 10% palladium on carbon (33 mg) in methanol (10 mL) was stirred under 4 atm hydrogen atmosphere at ambient temperature for 2 hours. The catalysts were filterred off and washed with chloroform. The filtrates were evaporated in vacuo to give 5-[3-(5-ethoxy-5-oxopentyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-4-yl]nicotinic acid as yellow oil (272 mg). 5-[3-(5-ethoxy-5-oxopentyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-4-yl]nicotinic acid 1H NMR (CDCb) o 1.21 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.35-1.63 (4H, m), 2.19 (2H, t, J= 7 Hz), 2.38-2.49 (2H, m), 2.57 (3H, s), 3.03 (2H, q, J= 7 Hz), 4.11 (2H, q, J= 7 Hz), 5.85 (1H, d, J= 4 Hz), 6.53 (1H, d, J= 4 Hz), 8.40 (1H, m), 8.83 (1H, d, J= 2 Hz), 9.37 (1H, d, J= 2 Hz). MS (ESI"): m/z 408, MS (ES1+): m/z410. Example 311 To a solution of 5-[3-(5-ethoxy-5-oxopentyl)-7-elhyl-2-methylpyrrolo[l,2-b]pyridazin-4-yl]nicotinic acid (235 mg) and triethylarnine (87.1 mg) in t-butanol (10 TIL) was added diphenylphosphoryl azide (237 mg) and the mixture was heated under reflux for 2 hours. After evaporation of solvent, the residue was partitioned between sthyl acetate and water. The organic layer was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and ethyl acetate (20:1 - 2:1) to give ethyl 5-(4-{5-[(tert-butoxycarbonyl)amino]-3-pyridinyl}-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl)pentanoate as yellow oil (190 mg). ethyl 5-(4-{5-[(tert-butoxycarbonyl)amino]-3-pyridinyl}-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl)pentanoate 1H NMR (CDC13) 8 1 -24 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.42-1.67 (4H, m), 1.52 (9H, s), 2.19-2.28 (2H, m), 2.38-2.50 (2H, m), 2.55 (3H, s), 3.03 (2H, q, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 5.92 (1H, d, J= 4 Hz), 6.53 (1H, d, J= 4 Hz), 6.93 (1H, br), 7.87 (1H, s), 8.30 (1H, d, J= 2 Hz), 8.70 (1H, d, J= 2 Hz). MS(ESI+):m/z481. Example 312 A solution of ethyl 5-(4-{5-[(tert-butoxycarbonyl)amino]-3-pyridinyl}-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl)pentanoate (190 mg) in 2 N hydrogen chloride ethyl acetate solution (4 mL) was stirred at ambient temperature for 2 hours. After evaporation of solvent, the residue was partitioned between ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of chloroform and methanol (100:1 -20:1) to give ethyl 5-[4-(5-amino-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate as yellow oil (140 mg). ethyl 5-[4-(5-amino-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3- yl]pentanoate 1H NMR (CDCI3) 5 1.24 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.40-1.65 (4H, m), 2.23 (2H, t, J= 7 Hz), 2.45 (2H, t, J= 7 Hz), 2.54 (3H, s), 3.03 (2H, q, J= 7 Hz), 3.97(2H,br),4.12(2H,q,J=7Hz),5.94(lH,d,J=4Hz),6.53(lH,d,J=4Hz), 7.02 (1H, m), 8.02 (1H, d, J= 2 Hz), 8.17 (1H, d, J= 2 Hz). MS (ESI+): m/z 381 (M+H). Example 313 To a solution of ethyl 5-[4-(5-amino-3-pyridinyl)-7-ethy]-2-methy]pyrroIo[l,2-b]pyridazin-3-yl]pentanoate (55 mg), 37% formaldehyde solution (277 mg) and sodium cyanoborohydride (27.3 mg) in acetnitrile (1 mL) and methanol (1 mL) was added acetic acid (2 drops) and the mixture was stirred at ambient temperature for 2 hours. The solution was diluted with saturated sodium bicarbonate solution and extracted with chloroform. The organic layer was washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by preparative silica gel column chromatography eluting with a mixture of chloroform and methanol (20:1) to give ethyl 5-{4-[5-(dimethylamino)-3-pyridinyl]-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl}pentanoate as yellow oil (36.5 mg). ethyl 5-{4-[5-(dimethylamino)-3-pyridinyl]-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl}pentanoate H NMR (CDC13) 6 1.23 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.40-1.63 (4H, m), 2.19 (2H, t, J= 7 Hz), 2.40-2.53 (2H, m), 2.55 (3H, s), 3.02 (6H, s), 3.03 (2H, q, J= 7 Hz), 4.09 (2H, q, J= 7 Hz), 5.93 (1H, d, J= 4 Hz), 6.50 (1H, d, J= 4 Hz), 6.96 (1H, m), 7.95 (1H, d, J= 2 Hz), 8.20 (1H, d, J= 2 Hz). MS(ESI+):m/z409. The following compound(s) was(were) obtained in substantially the same manner as that of Example 245. Example 314 3-[7-ethyl-4-(5-ethyl-3-pyridinyl)-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]propanoic acid 1H NMR (CDCI3) 6 1.29 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 2.45-2.58 (2H, m), 2.73 (2H, q, J= 7 Hz), 2.82-3.02 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.47 (3H, s), 4.67 (2H, s), 5.91 (1H, d, J= 4 Hz), 6.59 (1H, d, J= 4 Hz), 7.58 (1H, m), 8.43 (1H, d, J=2Hz),8.53(lH,d,J=2Hz). MS (ESI): m/z 366,MS (ESI+): m/z 368. Example 315 4-[7-ethyl-4-(5-ethyl-3-pyridinyl)-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]butanoic acid 1H NMR (CDCI3) 6 1.31 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 1.69-1.85 (2H, m), 2.20-2.31 (2H, m), 2.52-2.75 (2H, m), 2.77 (2H, q, J= 7 Hz), 3.06 (2H, q, J= 7 Hz), 3.46 (3H, s), 4.60-4.80 (2H, m), 5.91 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.61 (lH,s), 8.44-8.53 (2H,m). MS (ESI+): m/z 382. The following compound(s) was(were) obtained in substantially the same manner as that of Example 228. Example 316 methyl 4-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(hydroxymethyl)pyrrolo[l,2-b]pyridazin-3-yljbutanoate 1H NMR (CDCI3) 6 1.38 (3H, t, J= 7 Hz), 1.65-1.79 (2H, m), 2.25 (2H, t, J= 7 Hz), 2.39-2.53 (2H, m), 3.06 (2H, q, J= 7 Hz), 3.61 (3H, s), 4.90 (2H, s), 5.96 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.88 (1H, m), 8.55 (1H, d, J= 2 Hz), 8.79 (1H, d, J= 2 Hz). MS (ESI+): m/z 432 434 . Example 317 ethyl 5-[7-ethyl-2-(hydroxymethyl)-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3- yljpentanoate 1H NMR (CDCI3) 6 1.23 (3H, t, J= 7 Hz), 1.38 (3H,t, J= 7 Hz), 1.35-1.60 (4H,m), 2.17 (2H, t, J= 7 Hz), 2.35-2.45 (2H, m), 2.43 (3H, s), 3.04 (2H, q, J= 7 Hz), 3.83 (1H, t, J= 7 Hz), 4.10 (2H, q, J= 7 Hz), 4.85 (2H, d, J= 7 Hz), 5.96 (1H, d, J= 4 Hz), 6.57 (1H, d, J= 4 Hz), 7.50 (1H, s), 8.42 (1H, s), 8.54 (1H, s). MS (ESI+): m/z 396. The following compound(s) was(were) obtained in substantially the same manner as that of Example 268. Example 318 methyl 4-[4-(5-bromo-3-pyridiny])-7-ethyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]butanoate 1H NMR (CDCb) 6 1.37 (3H, t, J= 7 Hz), 1.65-1.79 (2H, m), 2.24 (2H, t, J= 7 Hz), 2.52-2.70 (2H, m), 3.04 (2H, q, J= 7 Hz), 3.46 (3H, s), 3.60 (3H, s), 4.76 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.88 (1H, m), 8.56 (1H, d, J= 2 Hz), 8.79(lH,d,J=2Hz). MS(ES1+):m/z446 448. Example 319 ethyl 5-[2-[(2-tert-butoxy-2-oxoethoxy)methyl]-7-ethyl-4-(5-methyl-3- pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate 1H NMR (CDCI3) 6 1.24 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.30-1.60 (4H, m), 1.47 (9H, s), 2.17 (2H, t, J= 7 Hz), 2.43 (3H, s), 2.58-2.72 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.08 (2H, s), 4.12 (2H, q, J= 7 Hz), 4.81 (2H, s), 5.91 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.53 (1H, s), 8.43 (1H, s), 8.53 (1H, s). MS(ESI+):m/z510. Example 320 ethyl 5-[2-[(cyclopropylmethoxy)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2- b]pyridazin-3-yl]pentanoate 1H NMR (CDCI3) 6 0.20-0.32 (2H, m), 0.53-0.63 (2H, m), 1.07-1.20 (1H, m), 1.22 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.40-1.60 (4H, m), 2.15 (2H, t, J= 7 Hz), 2.43 (3H, s), 2.53-2.68 (2H, m), 3.02 (2H, q, J= 7 Hz), 3.41 (2H, d, J= 7 Hz), 4.08 (2H, q, J= 7 Hz), 4.70 (2H, s), 5.89 (1H, d, J= 4 Hz), 6.56 (1H, d, J= 4 Hz), 7.52 (1H, s), 8.43 (1H, s), 8.53 (1H, s). MS(ESl+):m/z450. Example 321 ethyl 5-[2-[(cyclohexylmethoxy)methyl]-7-ethyl-4-(5-methyl-3-pyridiny])pyrrolo[l,2- b]pyridazin-3-yl]pentanoate 1H NMR (CDCI3) 6 0.88-1.05 (2H,m), 1.16-1.35 (4H, m), 1.25 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.38-1.59 (4H, m), 1.60-1.87 (5H, m), 2.16 (2H, t, J= 7 Hz), 2.43 (3H, s), 2.54-2.67 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.35 (2H, d, J= 7 Hz), 4.10 (2H, q, J= 7 Hz), 4.64 (2H, s), 5.89 (1H, d, J= 4 Hz), 6.56 (1H, d, J= 4 Hz), 7.52 (1H, s), 8.43 (1H, d, J= 2 Hz), 853 (1H, d, J= 2 Hz). MS(ESl+):m/z492. Example 322 ethyl 5-{7-ethyl-4-(5-methyl-3-pyridinyl)-2-[(3-pyridinylniethoxy)methy]]pyrrolo[ 1,2- b]pyridazin-3-yl}pentanoate 1H NMR (CDC13) 6 1.22 (3H, t, J= 7 Hz), 1.39 (3H, t, J= 7 Hz), 1.35-1.54 (4H, m), 2.12 (2H, t, J= 7 Hz), 2.43 (3H, s), 2.50-2.63 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.08 (2H, q, J= 7 Hz), 4.66 (2H, s), 4.76 (2H, s), 5.92 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 7.28 (1H, m), 7.52 (1H, s), 7.72 (1H, d, J= 8 Hz), 8.42 (1H, d, J= 2 Hz), 8.54 (2H, m), 8.62 (lH,d, J= 2 Hz). MS (ES1+): m/z 487. Example 323 ethyl 5-{7-ethyl-4-(5-methyl-3-pyridinyl)-2-[(2-pyridinylmethoxy)methyl]pyrrolo[l,2- b]pyridazin-3-yl}pentanoate 1H NMR (CDC13) 8 1.21 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 1.36-1.54 (4H, m), 2.12 (2H, t, J= 7 Hz), 2.42 (3H, s), 2.56-2.68 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.08 (2H, q, J= 7 Hz), 4.77 (2H, s),4.85 (2H, s), 5.92 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.22 (1H, m), 7.43-7.54 (2H, m), 7.66-7.74 (1H, m), 8.42 (1H, d, J= 2 Hz), 8.54 (1H, d, J= 2 Hz), 8.57 (1H, d, J= 5 Hz). MS (ESI+): m/z 487. Example 324 ethyl 5-{7-ethyl-4-(5-methyl-3-pyridinyl)-2-[(4-pyridinylmethoxy)methyl]pyrrolo[l,2- b]pyridazin-3-yl}pentanoate 1H NMR (CDCI3) 8 1.22 (3H, t, J= 7 Hz), 1.39 (3H, t, J= 7 Hz), 1.38-1.57 (4H,m), 2.12 (2H, t, J= 7 Hz), 2.43 (3H, s), 2.52-2.68 (2H, m), 3.05 (2H, q, J= 7 Hz), 4.08 (2H, q, J= 7 Hz), 4.66 (2H, s), 4.77 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 2 Hz), 7.28 (2H, d, J= 7 Hz), 7.52 (1H, s), 8.42 (1H, d, J= 2 Hz), 8.53 (1H, d, J= 2 Hz),8.58(2H,d,J=7Hz). MS(ESl+):m/z487. Example 325 ethyl 5-{7-ethyl-4-(5-melhyl-3-pyridinyl)-2-[(2-pyrazinylmethoxy)melhyl]pyrrolo[l,2-b]pyridazin-3-yl}pentanoate 1H NMR (CDCI3) 5 1 -22 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 1.38-1.57 (4H, m), 2.13 (2H, t, J= 7 Hz), 2.43 (3H, s), 2.52-2.68 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.07 (2H, q, J= 7 Hz), 4.82 (2H, s), 4.88 (2H, m), 5.92 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 7.52 (1H, s), 8.43 (1H, d, J= 2 Hz), 8.48-8.57 (3H, m), 8.75 (1H, m). MS (ESI+): m/z 488. Example 326 ethyl 5-[4-(3-cyanophenyl)-2-(ethoxymethyl)-7-ethylpyrrolo[l,2-b]pyridazin-3- yl]pentanoate 1H NMR (CDCI3) 8 1.18-1.29 (6H, m), 1.34-1.53 (7H, m), 2.14 (2H, t, J = 7 Hz), 2.52 (2H, m), 3.02 (2H, q, J= 7 Hz), 3.53 (2H, q, J = 7 Hz), 4.07 (2H, q, J = 7 Hz), 4.66 (1H, s), 5.73 (U, d, J = 5 Hz), 6.56 (1H, d, J = 5 Hz), 7.60 (2H, m), 7.67 (1H, s), 7.75 (1H, m) Example 327 ethyl 5-[2-[(benzyloxy)methyl]-4-(3-cyanophenyl)-7-ethylpyrrolo[l,2-b]pyridazin-3- yl]pentanoate 1H NMR (CDCI3) 6 1.22 (3H, t, J = 7 Hz), 1.30-1.46 (7H, m), 2.06 (2H, t, J = 7 Hz), 2.51 (2H, m), 3.02 (2H, q, J = 7 Hz), 4.07 (2H, q, J = 7 Hz), 4.64 (3H, s), 4.72 (3H, s), 5.83 (1H, d, J = 5 Hz), 6.57 (1H, d, J = 5 Hz), 7.25-7.38 (5H, m), 7.57 (2H, d, J = 9 Hz), 7.65 (1H, s), 7.74 (1H, m). Example 328 methyl 4-({[4-(3-cyanophenyl)-3-(5-ethoxy-5-oxopentyl)-7-ethylpyrrolo[l,2-b]pyridazin- 2-yl]methoxy}methyl)benzoate 1H NMR (CDCI3) 6 1.22 (3H, t, J = 7 Hz), 1.32-1.49 (7H, m), 2.01 (2H, t, J = 7 Hz), 2.52 (2H, m), 3.02 (2H, t, J = 7 Hz), 3.92 (3H, s), 4.07 (2H, t, J = 7 Hz), 4.69 (2H, s), 4.75 (2H, s), 6.84 (1H, d, J = 5 Hz), 6.59 (1H, d, J = 5 Hz), 7.43 (2H, d, J = 9 Hz), 7.60 (2H, m), 7.65 (1H, s), 7.75 (1H, m), 8.02 (2H, d, J = 9 Hz). Example 329 A solution of ethyl 5-[2-[(2-tert-buloxy-2-oxoethoxy)methyl]-7-ethyl-4-(5-methy]-3-pyridiny])pyrro]o[l,2-b]pyridazin-3-y]]pentanoate (60 mg) in tifluoroacetic acid (2 mL) was stirred at ambient temperature for 2 hours, and evaporated in vacuo to give {[3-(5-elhoxy-5-oxopenty])-7-ethyl-4-(5-methy]-3-pyridinyl)pyrrolo[l,2-b]pyridazin-2-yI]methoxy}acetic acid as brown oil (55 mg). {[3-(5-ethoxy-5-oxopenty])-7-ethyI-4-(5-methyl-3-pyridinyl)pyrro]o[l,2-b]pyridazin-2-yl]methoxy}acetic acid 1H NMR (CDC13) 6 1.25 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.35-1.60 (4H, m), 2.23 (2H, t, J= 7 Hz), 2.50-2.58 (2H, m), 2.67 (3H, s), 3.03 (2H, q, j= 7 Hz), 4.08 (2H, q, J= 7 Hz), 4.30 (2H, s), 4.87 (2H, s), 5.86 (1H, d, J= 4 Hz), 6.67 (1H, d, J= 4 Hz), 8.15 (1H, s), 8.69 (1H, s), 8.85 (1H, s). MS (ESI): m/z 452, MS (ESI+): m/z 454. Example 330 To a solution of {[3-(5-ethoxy-5-oxopentyl)-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-2-yl]methoxy}acetic acid (55 mg), l-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (34.9 mg) and 1-hydroxybenotriazole (24.6 mg) in dimethylformamide (2 mL) was added morpholine (12.7 mg) and the mixture was stirred at ambient temperature for 1 hour. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with saturated sodium bicarbonate solution, water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of ethyl acetate and methanol (50:1 - 20:1) to give ethyl 5-(7-ethyl-4-(5-methyl-3-pyridinyl)-2-{ [2-(4-morpholinyl)-2-oxoethoxy]methyl}pyrrolo[ 1,2-b]pyridazin-3-yl)pentanoate as yellow oil (50 mg). ethyl 5-(7-ethyl-4-(5-methyl'3-pyridinyl)-2-{[2-(4-morpholinyl)-2-oxoethoxy]methyl}pyrrolo[l ,2-b]pyridazin-3-yl)pentanoate 1HNMR(CDCl3)6l.22(3H,t,J=7Hz),1.37(3H,t,J=7Hz), 1.40-1.63 (4H,m), 2.15 (2H, t, J= 7 Hz), 2,43 (3H, s), 2.54-2.68 (2H, m), 3.02 (2H, q, J= 7 Hz), 3.48- 3.57 (2H, m), 3.63-3.78 (6H, m), 4.08 (2H, q, J= 7 Hz), 4.30 (2H, s), 4.78 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 7.52 (1H, s), 8.43 (1H, d, J= 2 Hz), 8.54(lH,d,J=2Hz). MS(ESI+):m/z523. The following compound(s) was(were) obtained in substantially the same manner as that of Example 330. ' Example 331 ethyl 5-[7-ethyl-2-{[2-(methylamino)-2-oxoethoxy]methyl}-4-(5-methyl-3- pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate 1H NMR (CDC13) 6 1.23 (3H, t, J= 7 Hz), 1.38 (3H,t, J= 7 Hz), 1.38-1.62 (4H,m), 2.18 (2H, t, J= 7 Hz), 2.44 (3H, s), 2.48-2.62 (2H, m), 2.88 (3H, d, J= 7 Hz), 3.03 (2H, q, J= 7 Hz), 4.11 (2H, q, J= 7 Hz), 4.13 (2H, s), 4.77 (2H, s), 5.94 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 6.79 (1H, br), 7.53 (1H, s), 8.44 (1H, s), 8.56 (1H, s). MS(ESI+):m/z467. The following compound(s) was(were) obtained in substantially the same manner as that of Example 271. Example 332 ethyl 5-[2-[(benzylamino)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[ 1,2- b]pyridazin-3-yl]pentanoate 1H NMR (CDCI3) 6 1.22 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 1.30-1.50 (2H, m), 1.60-1.85 (2H, m), 2.12 (2H, t, J= 7 Hz), 2.30-2.45 (2H, m), 2.42 (3H, s), 3.03 (2H, q, J= 7 Hz), 3.96 (2H, s), 3.98 (2H, s), 4.08 (2H, q, J= 7 Hz), 5.87 (1H, d, J= 4 Hz), 6.54 (1H, d, J= 4 Hz), 7.27-7.43 (5H, m), 7.48 (1H, s), 8.38 (1H, d, J= 2 Hz),8.53(lH,d,J=2Hz). MS(ESl+):m/z485. •Example 333 A mixture of ethyl 5-[7-ethyl-2-(hydroxymethyl)-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate (100 mg), lH-isoindole-l,3(2H) dione (44.6 mg) diisopropyl azodicarboxylate (76.7 mg) and triphenylphosphine (99.5 mg) in tetrahydrofuran (2 mL) was stirred at ambient temperature for 1 hour. After evaporation of solvent, the residue was purified by silica gel column chromatography eluling with a mixture of hexane and ethyl acetate (20:1 - 1:1) to give ethyl 5-[2-[(l,3-dioxo-l,3-dihydro-2H-isoindol-2-yl)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolofl,2-bJpyridazin-3-yl]pentanoate as yellow oil (107 mg). ethyl 5-[2-[(13-dioxo-13-dihydro-2H-isoindol-2-yl)methyl]-7-ethyl-4-5-methyl-3-pyridinyI)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate 1H NMR (CDC13) 6 0.89 (3H,t, J= 7 Hz), 1.26 (3H, t, J= 7 Hz), 1.20-1.40 (2H, m), 1.53-1.75 (2H, m), 2.24 (2H, t, J= 7 Hz), 2.44 (3H, s), 2.47 (2H, q, J= 7 Hz), 2.50-2.64 (2H, m), 4.12 (2H, q, J=; 7 Hz), 5.10 (2H, s), 5.85 (1H, d, J= 4 Hz), 6.43 (1H, d, J= 4 Hz), 7.51 (1H, s), 7.78 (2H, m), 7.96 (2H, m), 8.43 (1H, s), 8.55 (1H, s). MS(ESI+):m/z525. Example 334 A mixture of ethyl 5-[2-[(l,3-dioxo-l,3-dihydro-2H-isoindol-2-yl)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate (107 mg) and hydrazine monohydrate (51.1 mg) in ethanol (2 mL) was heated under reflux for 2 hours. After evaporation of solvent, the residue was partitioned between chloroform and saturated sodium bicarbonate solution. The organic layer was separated, washed with brine, dried over magnesium sulfate, and evaporated in vacuo to give ethyl 5-[2-(aminomethyl)-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate as yellow oil (67.6 mg). ethyl 5-[2-(aminomethyl)-7-ethyl-4-(5-methyl-3-pyridiny])pyrrolo[ 1,2-b]pyridazin-3-yl]pentanoate 1H NMR (CDCI3) 6 1.23 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 1.38-1.62 (4H, m), 2.14 (2H> t, J= 7 Hz), 2.42 (3H, s), 2.38-2.56 (2H, m), 3.04 (2H, q, J= 7 Hz), 4.06 (2H, s), 4.08 (2H, q, J= 7 Hz), 5.90 (1H, d, J= 4 Hz), 6.55 (1H, d, J= 4 Hz), 7.51 (lH,s), 8.41 (lH,s), 8.53 (lH,s). MS(ESl+):m/z395. Example 335 A mixture of ethyl 5-[2-(aminomethyl)-7-ethyl-4-(5-methyl-3- pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoale (67.6 mg) and acetic anhydride (19.2 mg) in dichloromethane (3 mL) was stirred at ambient temperature for 1 hour. The solution was diluted with chloroform, washed with saturated sodium bicarbonate solution and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by preparative silica gel column chromatography eluting with a mixture of chloroform and methanol (20:1) to give ethyl 5-[2-[(acetylamino)melhyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate as yellow oil (70 mg). ethyl 5-[2"[(acetylamino)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate 1HNMR(CDCl3)6l.22(3H5t,J=7Hz),1.40(3H,t,J=7Hz),1.40-1.63(4H,m)5 2.12 (2H, m), 2.15 (3H, s), 2.43 (3H, s), 2.40-2.53 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.10 (2H, q, J= 7 Hz), 4.66 (2H, m), 5.94 (1H, d, J= 4 Hz), 6.59 (1H, d, J= 4 Hz), 6.85 (1H, br), 7.50 (1H, s), 8.40 (1H, d, J= 2 Hz), 8.54 (1H, d, J= 2 Hz). MS(ESI+):m/z437. Example 336 To a solution of ethyl 5-[2-(aminomethyl)-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yI]pentanoate (80 mg) and pyridine (1 mL) in dichloromethane (2 mL) was added methanesulfonyl chloride (34.8 mg) under ice-water cooling and the mixture was stirred at ambient temperature for 1 hour. The solution was diluted with chloroform, washed with saturated sodium bicarbonate solution and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by preparative silica gel column chromatography eluting with a mixture of chloroform and methanol (20:1) to give ethyl 5-(7-ethyl-4-(5-methyl-3-pyridinyl)-2-{[(methylsulfonyl)amino]methyl}pyrrolo[l,2-b]pyridazin-3-yl)pentanoate as yellow oil (62.8 mg) ethyl 5-(7-ethyl-4-(5-methyl-3-pyridinyl)-2-{[(methylsulfonyl)amino]methyl}pyrrolo[l,2- b]pyridazin-3-yl)pentanoate 1H NMR (CDC13) 6 1.23 (3H, t, J= 7 Hz), 1.39 (3H, t, J= 7 Hz), 1.40-1.62 (4H, m), 2.19 (2H, t, J= 7 Hz), 2.44 (3H, s), 2.38-2.51 (2H, m), 3.02 (2H, q, J= 7 Hz), 3.06 (3H, s), 4.08 (2H, q, J= 7 Hz), 4.58 (2H, s), 5.63 (1H, br), 5.97 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.50 (1H, s), 8.41 (1H, d, J= 2 Hz), 8.54 (1H, d, J= 2 Hz). MS(ESl+):m/z473. Example 337 A mixture of ethyl 5-[2-(aminomethyl)-7-etbyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate (75 mg), benzoic acid (27.9 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (54.7 mg) and 1-hydroxybenotriazole (38.5 mg) in dimethylformamide (2 mL) was stirred at ambient temperature for 2 hours. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with saturated sodium bicarbonate solution, water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by preparative silica gel column chromatography eluting with a mixture of chloroform and methanol (20:1) to give ethyl 5-[2-[(benzoylamino)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate as yellow oil (60 mg). ethyl 5-[2-[(benzoylamino)methyl]-7-ethyl-4-(5»methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate 1H NMR (CDC13) 5 1.23 (3H, t, J= 7 Hz), 1.42 (3H, t, J= 7 Hz), 1.42-1.65 (4H, m), 2.17 (2H, t, J= 7 Hz), 2.44 (3H, s), 2.44-2.58 (2H, m), 3.06 (2H, q, J= 7 Hz), 4.08 (2H, q, J= 7 Hz), 4.86 (2H, m), 5.96 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 7.46- 7.59 (4H, m), 7.78 (1H, br), 7.91-7.97 (2H, m), 8.44 (1H, d, J= 2 Hz), 8.56 (1H, d, J= 2 Hz). MS (ES1+): m/z 499. The following compound(s) was(were) obtained in substantially the same manner as that of Example 337. Example 338 ethyl5-(7-ethyl-4-(5-methyl-3-pyridinyl)-2-{[(2-pyrazinylcarbonyl)amino]methyl}pyrrolofl,2-b]pyridazin-3-yl)pentanoate 1H NMR (CDCI3) 5 1.23 (3H,t, J= 7 Hz), 1.41 (3H, t, J= 7 Hz), 1.42-1.64 (4H,m), 2.18 (2H, t, J= 7 Hz), 2.44 (3H, s), 2.47-2.59 (2H, m)> 3.08 (2H, q, J= 7 Hz), 4.09 (2H, q, J= 7 Hz), 4.89 (2H, d, J= 7 Hz), 5.96 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 7.53 (1H, s), 8.43 (1H, d, J= 2 Hz), 8.55 (1H, d, J= 2 Hz), 8.62 (1H, m), 8.79 (1H, m), 9.15 (1H, br), 9.46 (1H, m). MS(ESI+):m/z501. Example 339 To a solution of ethyl 5-[2-(aminomethyl)-7-etbyl-4-(5-methyl-3-pyridinyl)pyrrolo[l ,2-b]pyridazin-3-yl]pentanoate (80 mg) and pyridine (1 mL) in dichloromethane (2 mL) was added methyl chloridocarbonate (34.8 mg) under ice-water cooling and the mixture was stirred at ambient temperature for 2 hours. After evaporation of solvent, the residue was partitioned between ethyl acetate and water. The organic layer was separated, washed with saturated sodium bicarbonate solution and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by preparative silica gel column chromatography eluting with a mixture of chloroform and methanol (20:1) to give ethyl 5-[7-ethyl-2-{[(methoxycarbonyl)amino]methyl}-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate as yellow oil (70 mg). ethyl 5-[7-ethyl-2-{[(methoxycarbonyl)amino]methyl}-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate 1HNMR (CDC13) 6 1.23 (3H, t, J= 7 Hz), 1.39 (3H, t, J= 7 Hz), 1.40-1.63 (4H, m), 2.19 (2H, t, J= 7 Hz), 2.44 (3H, s), 2.40-2.55 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.07 (3H, s), 4.12 (2H, q, J= 7 Hz), 4.57 (2H,m), 5.72 (1H, br), 5.97 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.51 (1H, s), 8.41 (1H, s), 8.56 (1H, s). Example 340 To a solution of ethyl 5-[4-(3-cyanophenyl)-7-ethyl-2-(hydroxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate (70.0 mg) and triethyl amine (18.5 mg) in dichloromethane (1 mL) was added methanesulfonyl chloride (20.9 mg) under an ice bath. After stirring for 1 hour, to the mixture was added 1-methylpiperazine (27.0 mg). The mixture was stirred for 0.5 hour under an ice bath and overnight at room temperature. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over magnesium sulfate, and evaporated. Preparative silicagel thin layer chromatography (chloroform-methanol = 20-1) afforded ethyl 5-{4-(5-bromo-3-pyridinyl)-7-ethyl-2-[(4-methyl-l-piperazinyl)methyl]pyrroIo[l,2-b]pyridazin-3-yljpentanoate as an yellow gum (52.4 mg, 63.5%). ethyl 5-{4-(5-bromo-3-pyridinyl)-7-ethyl-2-[(4-rnethy]-l-piperazinyl)methyI]pyrro]o[l,2- b]pyridazin-3-yl}pentanoate 1H NMR (CDC13): 1.23 (3H, t, J = 7 Hz), 1.33-1.60 (7 H, m), 2.16 (2H, t, J = 7 Hz), 2.29 (3H, s), 2.34-2.65 (6H, m), 3.00 (2H, q, J = 7 Hz), 3.54 (2H, s), 4.08 (2H, q, J = 7 Hz), 5.86 (1H, d, J = 5 Hz), 6.55 (1H, d, J = 5 Hz9,7.87 (1H, m), 8.54 (1H, m),8.77(lH,m). Example 341 To a solution of ethyl 5-[4-(3-cyanophenyl)-7-ethyl-2-(hydroxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate (300 mg, 0.652 mmol) and tetrabromomethane (432 mg, 1.30 mmol) in tetrahydrofuran (3 mL) was added triphenylphosphine (308 mg, 1.17 mmol) over 40 minutes. The mixture was concentrated, and the residue was chromatographed on a flash silica gel column chromatography (ethyl acetate-hexane = 1-8 to 1-5) to afford ethyl 5-[2-(bromomethyl)-4-(5-bromo-3-pyridinyl)-7-ethylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate as an yellow gum (229 mg, 50.4%). ethyl 5-[2-(bromomethyl)-4-(5-bromo-3-pyridinyl)-7-ethylpyrrolo[l,2-b]pyridazin-3- yl]pentanoate 1H NMR (CDC13) 5 1.23 (3H,t, J = 7 Hz), 1.37 (3H, t, J = 7 Hz), 1.41-1.50 (4H,m), 2.19 (2H, t, J = 7 Hz), 2.58 (2H, m), 3.01 (2H, q, J = 7 Hz), 4.08 (2H, q, J = 7 Hz), 4.66 (2H, s), 5.94 (1H, d, J = 5 Hz), 6.63 (1H, d, J = 5 Hz), 7.88 (1H, m), 8.55 (lH,m),8.79(lH,m). Example 342 A mixture of ethyl 5-[2-(bromomethyl)-4-(5-bromo-3-pyridinyl)-7-ethylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate (70.0 mg) and potassium cyanide (13.1 mg) in N,N-dimethylformamide (1 mL) was stirred for 28 hours at room temperature. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with water (two times), brine, dried over magnesium sulfate, and evaporated to give ethyl 5-[4-(5-bromo-3-pyridinyl)-2-(cyanomethyl)-7-ethylpyrrolo[l,2-b]pyridazin-3-yljpentanoate as an yellow gum (28.8 mg, 45.9%). ethyl 5-[4-(5-bromo-3-pyridiny])-2-(cyanomethyl)-7-ethylpyrrolo[l,2-b]pyridazin-3-y]]pentanoate 1H NMR (CDCI3) 6 1.24 (3H,t, J = 7 Hz), 1.46-1.65 (7H,m),2.22 (2H,t, J = 7 Hz), 2.48 (2H, m), 3.04 (2H, q, J = 7 Hz), 3.98 (2H, s), 4.10 (2H, q, J = 7 Hz), 5.98 (1H, d, J = 5 Hz), 6.65 (1H, d, J = 5 Hz), 7.88 (1H, m), 8.55 (1H, m), 8.81 (1H, m). The following compound(s) was(were) obtained in substantially the same manner as that of Example 76. Example 343 [7-ethyl-2-methyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]aceticacid 1H NMR (CDCI3) 6 1.36 (3H, t, J= 7 Hz), 2.45 (3H, s), 2.56 (3H, s), 3.02 (2H, q, J= 7 Hz), 3.28 (1H, d, J= 17 Hz), 3.53 (1H, d, J= 17 Hz), 5.91 (1H, d, J= 4 Hz), 6.52 (1H, d, J= 4 Hz), 7.71 (1H, s), 8.47 (1H, s), 8.59 (1H, s). MS (ESI'): m/z 308, MS (ESI+): m/z 310. Example 344 4-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]butanoic acid 1H NMR (CDCI3) 6 1.38 (3H, t, J= 7 Hz), 1.65-1.85 (2H, m), 2.31 (2H, t, J= 7 Hz), 2.45-2.63 (2H, m), 2.59 (3H, s), 3.03 (2H, q, J= 7 Hz), 5.88 (1H, d, J= 4 Hz), 6.53 (1H, d, J= 4 Hz), 7.90 (1H, s), 8.53 (1H, s), 8.75 (1H, s). MS (ESI"): m/z 400 402, MS (ES1+): m/z 402 404. Example 345 4-[4-(5-acetyl-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]butanoicacid 1H NMR (CDCI3) 6 1.38 (3H, t, J= 7 Hz), 1.68-1.82 (2H, m), 2.26 (2H, t, J= 7 Hz), 2.45-2.58 (2H, m), 2.60 (3H, s), 2.70 (3H, s), 3.03 (2H, q, J= 7 Hz), 5.83 (1H, d, J= 4 Hz), 6.54 (1H, d, J= 4 Hz), 8.28 (1H, m), 8.77 (1H, d, J= 2 Hz), 9.19 (1H, d, J= 2 Hz). Example 346 3-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3- y]]propanoic acid 1H NMR (CDCI3) 8 1.37 (3H, t, J= 7 Hz), 2.49 (2H, t, J= 7 Hz), 2.80-3.00 (2H, m), 3.05 (2H, q, J= 7 Hz), 3.46 (3H, s), 4.66 (2H, s), 5.94 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.88 (1H, s), 8.55 (1H, s), 8.77 (1H, s). MS (ESI"): m/z 416 418, MS (ESI+): m/z 418 420. Example 347 3-[4-(5-acetyl-3-pyridinyl)-7-ethyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]propanoic acid 1H NMR (CDCI3) 8 1.38 (3H, t, J= 7 Hz), 2.48 (2H, t, J= 7 Hz), 2.68 (3H, s), 2.85-2.97 (2H, m), 3.05 (2H, q, J= 7 Hz), 3.47 (3H, s), 4.67 (2H, s), 5.88 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 8.27 (1H, m), 8.78 (1H, d, J= 2 Hz), 9.23 (1H, d, J= 2 Hz). MS (ESI"): m/z 380, MS (ESI+): m/z 382. Example 348 3-[7-ethyl-2-(methoxymethyl)-4-(5-vinyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]propanoic acid 1H NMR (CDCb) 8 1.38 (3H, t, J= 7 Hz), 2.46-2.58 (2H, m), 2.83-3.03 (2H, m), 3.05 (2H, q, J= 7 Hz), 3.47 (3H, s), 4.68 (2H, s), 5.46 (1H, d, J= 11 Hz), 5.88 (1H, d, J= 18 Hz), 5.93 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 6.68-6.82 (1H, dd, J= 11 Hz, 18 Hz), 7.78 (1H, m), 8.47 (1H, d, J= 2 Hz), 8.68 (1H, d, J= 2 Hz). MS (ESI"): m/z 364, MS (ESI+): m/z 366. Example 349 4-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(methoxymethyl)pyrro]o[l,2-b]pyridazin-3-yljbutanoic acid 1H NMR (CDCI3) 8 1.37 (3H, t, J= 7 Hz), 1.68-1.82 (2H, m), 2.29 (2H, t, J= 7 Hz), 2.55-2.75 (2H, m), 3.04 (2H, q, J= 7 Hz), 3.45 (3H, s), 4.64 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.61 (1H,d,J= 4 Hz), 7.91 (1H,m), 8.56 (1H,d, J= 2 Hz), 8.77 (1H,d, J=2Hz). MS (ESI'): m/z 430 432, MS (ESI+): m/z 432 434. Example 350 4-[7-ethyl-2-(methoxymethyl)-4-(5-vinyl-3-pyridinyl)pyrro]o[l,2-b]pyridazin-3-yljbutanoic acid 1H NMR (CDC13) 6 1.38 (3H, t, J= 7 Hz), 1.72-1.87 (2H, m), 2.26 (2H, t, J= 7 Hz), 2.53-2.80 (2H, m), 3.06 (2H, q, J= 7 Hz), 3.46 (3H, s), 4.68 (2H, m), 5.47 (1H, d, J= 11 Hz), 5.88 (1H, d, J= 18 Hz), 5.93 (1H, d, J= 4 Hz), 6.59 (1H, d, J= 4 Hz), 6.72-6.83 (1H, dd, J= 11 Hz, 18 Hz), 7.81 (1H, m), 8.50 (1H, d, J= 2 Hz), 8.63 (lH,d,J=2Hz). MS (ESI): m/z 378, MS (ESI+): m/z 380. Example 351 4-[4-(5-acetyl-3-pyridinyl)-7-ethyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]butanoic acid 2H NMR (CDC13) 6 1.38 (3H, t, J= 7 Hz), 1.66-1.83 (2H, m), 2.26 (2H, t, J= 7 Hz), 2.55-2.70 (2H, m), 2.70 (3H, s), 3.05 (2H, q, J= 7 Hz), 3.46 (3H, s), 4.67 (2H, s), 5.88 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz),8.29 (1H, m), 8.80 (1H, d, J= 2 Hz), 9.22(lH,d,J=2Hz). MS (ESI): m/z 394 , MS (ESI+): m/z 396. Example 352 5-[4-(5-amino-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid :H NMR (CDCI3) 5 1.34 (3H, t, J= 7 Hz), 1.44-1.65 (4H,m), 2.16-2.32 (2H,m), 2.34-2.46 (2H, m), 2.53 (3H, s), 3.02 (2H, q, J= 7 Hz), 5.06 (2H, br), 5.86 (1H, d, J= 4 Hz), 5.98 (1H, d, J= 4 Hz), 7.45 (1H, s), 7.84 (1H, s), 8.58 (1H, s). MS (ESI"): m/z 351, MS (ES1+): m/z 353. Example 353 5-{4-[5-(dimethylamino)-3-pyridinyl]-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl}pentanoic acid 1H NMR (CDCI3) 5 1.37 (3H, t, J= 7 Hz), 1.40-1.70 (4H, m), 2.23 (2H, m), 2.36-2.50 (2H, m), 2.56 (3H, s), 3.03 (2H, q, J= 7 Hz), 3.06 (6H, s), 5.88 (1H, d, J= 4 Hz), 6.53 (1H, d, J= 4 Hz), 7.13 (1H, s), 7.90 (1H, s), 8.14 (1H, m). MS (ES1+): m/z 381. Example 354 3-[4-(5-acetyl-3-pyridinyl)-7-ethy]-2-methy]pyrrolo[l,2-b]pyridazin-3-yl]propanoicacid 1H NMR (CDCI3) 5 1.37 (3H, t, J= 7 Hz), 2.40-2.53 (2H, m), 2.60 (3H, s), 2.68 (3H, s), 2.83 (2H, t, J= 7 Hz), 3.03 (2H, q, J= 7 Hz), 5.83 (1H, d, J= 4 Hz), 6.53 (1H, d, J= 4 Hz), 8.27 (1H, m), 8.78 (1H, d, J= 2 Hz), 9.22 (1H, d, J= 2 Hz). MS (ESI): m/z 350, MS (ESI+): m/z 352. Example 355 5-[2-[(benzyloxy)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid !H NMR (CDCb) 8 1.37 (3H, t, J= 7 Hz), 1.35-1.55 (4H, m), 2.05-2.20 (2H, m), 2.42 (3H, s), 2.40-2.70 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.63 (2H, s), 4.74 (2H, m), 5.88 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.27-7.42 (5H, m), 7.53 (1H, s), 8.40 (1H, s),8.53(lH,s). MS(ESI+):m/z458. Example 356 3-[2-[(benzyloxy)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]propanoic acid 1H NMR (CDCI3) 5 1.38 (3H, t, J= 7 Hz), 2.40 (3H, s), 2.40-2.54 (2H, m), 2.80-3.08 (2H, m), 3.06 (2H, q, J= 7 Hz), 4.65 (2H, s), 4.77 (2H, m), 5.89 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.26-7.42 (5H, m), 7.54 (1H, s), 8.39 (1H, d, J= 2 Hz), 8.48 (lH,d,J=2Hz). MS (ESI"): m/z 428, MS (ESI+): m/z 430. Example 357 5-[2-[(cyclohexyloxy)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3- yl]penlanoic acid 1H NMR (CDCI3) 5 1.20-1.45 (6H, m), 1.36 (3H, t, J= 7 Hz), 1.45-1.63 (4H, m), 1.70-1.83 (2H, m), 1.95-2.08 (2H, m), 2.14-2.28 (2H, m), 2.42 (3H, s), 2.46-2.60 (1H, m), 2.60-2.75 (1H, m), 3.03 (2H, q, J= 7 Hz), 3.42-3.54 (1H, m), 4.72 (2H, m), 5.87 (1H, d, J= 4 Hz), 6.54 (1H, d, J= 4 Hz), 7.55 (1H, s), 8.41 (1H, s), 8.53 (lH,s). MS (ESI"): m/z 448, MS (ESI4): m/z 450. Example 358 5-{4-(5-bromo-3-pyriclinyl)-2-[(cyclohexy]oxy)methyl]-7-ethylpyrro]o[l,2-b]pyridazin-3-yljpentanoicacid 1H NMR (CDC13) 8 1.18-1.60 (10H, m), 1.36 (3H, t, J= 7 Hz), 1.70-1.80 (2H, m), 1.95-2.05 (2H, m), 2.22 (2H, t, J= 7 Hz), 2.50-2.70 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.42-3.53 (1H, m), 4.68 (2H, s), 5.89 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.88 (1H, s), 8.54 (1H, d, J= 2 Hz), 8.77 (1H, d, J= 2 Hz). MS(ESI+):m/z514 516. Example 359 3-[2-[(cyclohexyloxy)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]propanoic acid 1H NMR (CDCI3) 6 1.20-1.45 (5H, m), 1.37 (3H, t, J= 7 Hz), 1.50-1.60 (1H, m), 1.72-1.84 (2H, m), 1.96-2.08 (2H, m), 2.42 (3H, s), 2.48-2.62 (2H, m), 2.80-3.10 . (2H, m), 3.03 (2H, q, J= 7 Hz), 3.44-3.66 (1H, m), 4.73 (2H, s), 5.88 (1H, d, J= 4 Hz), 6.57 (1H, d, J= 4 Hz), 7.55 (1H, s), 8.40 (1H, s), 8.51 (1H, s). MS (ESI+): m/z 422. Example 360 3-{4-(5-bromo-3-pyridinyl)-2-[(cyclohexyloxy)methyl]-7-ethylpyrrolo[l,2-b]pyridazin-3-yl}propanoic acid 1H NMR (CDCI3) 6 1.18-1.47 (5H, m), 1.37 (3H, t, J= 7 Hz), 1.52-1.63 (1H, m), 1.72-1.85 (2H, m), 1.97-2.07 (2H, m), 2.48-2.62 (2H, m), 2.80-3.10 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.44-3.57 (1H, m), 4.73 (2H, s), 5.91 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.88 (1H, t, J= 2 Hz), 8.55 (1H, d, J= 2 Hz), 8.77 (1H, d, J= 2 Hz). MS (ESI"): m/z 484 486, MS (ESI+): m/z 486 488. Example 361 5-[7-ethyl-2-(isopropoxymethyl)-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yljpentanoic acid 1H NMR (CDCI3) 6 1.25 (6H, d, J= 7 Hz), 1.37 (3H, 1, J= 7 Hz), 1.44-1.63 (4H, m), 2.15-2.27 (2H, m), 2.43 (3H, s), 2.47-2.60 (1H, m), 2.60-2.73 (1H, m), 3.03 (2H, q, J= 7 Hz), 3.75-3.87 (1H, m), 4.67 (2H, s), 5.87 (1H, d, J= 4 Hz), 6.56 (1H, d, J= 4 Hz), 7.55 (1H, s), 8.41 (1H, s), 8.53 (1H, s). MS (ESI"): m/z 408, MS (ESI+): m/z 410. Example 362 5-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(isopropoxymethyl)pyrrolo[l,2-b]pyridazin-3-y]]pentanoic kcid 1H NMR (CDCb) 6 1.25 (6H, d, J= 7 Hz), 1.36 (3H, t, J= 7 Hz), 1.45-1.65 (4H, m), 2.23 (2H, t, J= 7 Hz), 2.50-2.60 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.75-3.85 (1H, m), 4.66 (2H, s), 5.89 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.89 (1H, m), 8.54 (1H, d, J= 2 Hz), 8.77 (1H, d, J= 2 Hz). MS (ESI+): m/z 474 476. Example 363 5-[7-ethyl-2-(hydroxymethyl)-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yljpentanoic acid 1HNMR (CDCI3) 6 1.38 (3H, t, J= 7 Hz), 1.40-1.65 (4H, m), 2.22 (2H, t, J= 7 Hz), 2.33-2.45 (2H, m), 2.43 (3H, s), 3.03 (2H, q, J= 7 Hz), 4.87 (2H, s), 5.94 (1H, d, J= 4 Hz), 6.57 (1H, d, J= 4 Hz), 7.56 (1H, s), 8.43 (1H, s), 8.54 (1H, s). MS (ESI): m/z 366, MS (ES1+): m/z 368. Example 364 5-(7-ethyl-4-(5-methyl-3-pyridinyl)-2-{[2-(4-morpholinyl)-2- oxoelhoxy]methyl}pyrrolo[l,2-b]pyridazin-3-yl)pentanoicacid 1H NMR (CDCI3) 5 1.37 (3H, t, J= 7 Hz), 1.40-1.63 (4H, m), 2.22 (2H, t, J= 7 Hz), 2.43 (3H, s), 2.50-2.72 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.51 (2H, m), 3.57-3.75 (6H, m),4.32 (2H, s), 4.70-4.86 (2H, m), 5.90 (1H, d, J= 4 Hz), 6.59 (1H, d, J= 4 Hz), 7.53 (1H, s), 8.42 (1H, s), 8.53 (1H, s). MS (ESI"): m/z 493, MS (ESI+): m/z 495. Example 365 5-[7-ethyl-2-{[2-(methylamino)-2-oxoethoxy]methyl}-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-y]]pentanoic acid 1H NMR (CDCI3) 6 1.37 (3H, t, J= 7 Hz), 1.40-1.65 (4H, m), 2.22 (2H, t, J= 7 Hz), 2.44 (3H, s), 2.45-2.64 (2H5 m), 2.87 (3H, m), 3.03 (2H, q, J= 7 Hz), 4.13 (2H, s), 4.74 (2H, m), 5.93 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 6.83 (1H, br), 7.57 (lH,s), 8.42 (lH,s), 8.53 (lH,s). MS (ESI"): m/z 437, MS (ES1+): m/z 439. Example 366 5-[2-[(cyclopropylmethoxy)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-3]pyridazin-3-yl]pentanoic acid 1H NMR (CDCI3) 6 0.23-0.33 (2H, m), 0.55-0.64 (2H, m), 1.07-1.22 (1H, m), 1.36 (3H, t, J= 7 Hz), 1.45-1.68 (4H, m), 2.19 (2H, t, J= 7 Hz), 2.43 (3H, s), 2.50-2.75 (2H, m), 3.02 (2H, q, J= 7 Hz), 3.40 (2H, d, J= 7 Hz), 4.70 (2H, m), 5.87 (1H, d, J= 4 Hz), 6.56 (1H, d, J= 4 Hz), 7.57 (1H, s), 8.40 (1H, s), 8.54 (1H, s). MS (ESI+): m/z 422. Example 367 5-[2-[(cyclohexylmethoxy)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid 1H NMR (CDCI3) 5 0.87-1.04 (2H, m), 1.10-1.82 (13H, m), 1.37 (3H, t, J= 7 Hz), 2.18 (2H, t, J= 7 Hz), 2.43 (3H, s), 2.47-2.72 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.33 (2H, d, J= 7 Hz), 4.63 (2H, m), 5.87 (1H, d, J= 4 Hz), 6.56 (1H, d, J= 4 Hz), 7.56 (1H, s), 8.42 (1H, s), 8.53 (1H, s). MS (ESI"): m/z 462, MS (ESI+): m/z 464. Example 368 5-{7-ethyl-4-(5-methyl-3-pyridinyl)-2-[(3-pyridinylmethoxy)methyl]pyrrolo[l,2- b]pyridazin-3-yl}pentanoic acid 1H NMR (CDCI3) 6 1.38 (3H, t, J= 7 Hz), 1.35-1.57 (4H, m), 2.13 (2H, t, J= 7 Hz), 2.42 (3H, s), 2.47-2.66 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.68 (2H, s), 4.77 (2H, m), 5.90 (1H, d, J= 4 Hz), 6.59 (1H, d, J= 4 Hz), 7.28-7.36 (1H, m), 7.53 (1H, s), 7.73 (1H, d, J= 8 Hz), 8.41 (1H, d, J= 2 Hz), 8.53 (2H, m), 8.63 (1H, s). MS (ESI"): m/z 457, MS (ES1+): m/z 459. Example 369 5-{7-elhyl-4-(5-methyl-3-pyridiny])-2-[(2-pyridiny]methoxy)methyl]pyrrolo[l,2-b]pyridazin-3-yl}pentanoic acid 1H NMR (CDC13) 6 1.37 (3H, t, J= 7 Hz), 1.45-1.65 (4H, m), 2.23 (2H, t, J= 7 Hz), 2.41 (3H, s), 2.48-2.74 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.80 (2H, s), 4.82 (2H, m), 5.88 (1H, d, J= 4 Hz), 6.57 (1H, d, J= 4 Hz), 7.26 (1H, m), 7.47-7.53 (2H, m), 7.69-7.77 (1H, m), 8.42 (1H, d, J= 2 Hz), 8.50 (1H, d, J= 2 Hz), 8.58 (1H, d, J= 7 Hz). MS (ESI): m/z 457, MS (ESI+): m/z 459. Example 370 5-{7-ethyl-4-(5-methyl-3-pyridinyl)-2-[(4-pyridinylmethoxy)methyl]pyrrolo[l,2- b]pyridazin-3-yl}pentanoic acid 1H NMR (CDCI3) 6 1.38 (3H, t, J= 7 Hz), 1.40-1.62 (4H, m), 2.16 (2H, t, J= 7 Hz), 2.43 (3H, s), 2.48-2.71 (2H, m), 3.02 (2H, q, J= 7 Hz), 4.68 (2H, s), 4.79 (2H, m), 5.91 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 7.32 (2H, d, J= 7 Hz), 7.54 (1H, s), 8.42 (1H, d, J= 2 Hz), 8.54 (1H, d, J= 2 Hz), 8.55 (2H, d, J= 7 Hz). MS (ESI): m/z 457, MS (ESI+): m/z 459. Example 371 5-{7-ethyl-4-(5-methyl-3-pyridinyl)-2-[(2-pyrazinylmethoxy)methyl]pyrroIo[l,2-b]pyridazin-3-yl}pentanoic acid 1H NMR (CDCI3) 6 1.37 (3H, t, J= 7 Hz), 1.45-1.62 (4H, m), 2.18 (2H, t, J= 7 Hz), 2.43 (3H, s), 2.48-2.73 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.83 (2H, s), 4.88 (2H, m), 5.90 (1H, d, J= 4 Hz), 6.59 (1H, d, J= 4 Hz), 7.54 (1H, s), 8.42 (1H, s), 8.48-8.56 (3H,m),8.76(lH,s). MS (ES1+): m/z 458, MS (ESI+): m/z 460. Example 372 5-[2-[(benzylamino)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid 1H NMR (DMSO-d6) 6 1.33 (3H, t, J= 7 Hz), 1.28-3.48 (4H, m), 2.03-2.13 (2H, m), 2.30-2.45 (2H, m), 2.40 (3H, s), 3.06 (2H, q, J= 7 Hz), 4.37 (2H, s), 4.46 (2H, s), 5.92 (1H, d, J= 4 Hz), 6.68 (1H, d, J= 4 Hz), 7.40-7.52 (3H, m), 7.56-7.67 (3H, m), 8.36 (1H, d, J= 2 Hz), 8.57 (1H, d, J= 2 Hz). MS (ESI+): m/z 457. Example 373 5-[2-[(acetylamino)methyl]-7-ethyl-4-(5-methyl-3-pyridiny])pyrro]o[l,2-b]pyiidazin-3-yljpentanoic acid 1H NMR (CDC13) 6 1.40 (3H, t, J= 7 Hz), 1.40-1.64 (4H, m), 2.16 (3H, s), 2.23 (2H, t, J= 7 Hz), 2.35-2.50 (2H, m), 2.43 (3H, s), 3.03 (2H, q, J= 7 Hz), 4.63-4.72 (2H, m), 5.92 (1H, d, J= 4 Hz), 6.57 (1H, d, J= 4 Hz), 6.88-6.97 (1H, br), 7.53 (1H, s), 8.41 (lH,s), 8.53 (lH,s). MS (ESI"): m/z 407, MS (ESI+): m/z 409. Example 374 5-(7-ethyl-4-(5-methyl-3-pyridinyl)-2-{[(methylsulfonyl)amino]methyl}pyrrolo[l,2-b]pyridazin-3-yl)pentanoic acid 1H NMR (CDCI3) 6 1.38 (3H, t, J= 7 Hz), 1.46-1.66 (4H, m), 2.23 (2H, t, J= 7 Hz), 2.44 (3H, s), 2.39-2.53 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.05 (3H, s), 4.57 (2H, s), 5.72 (1H, br), 5.96 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.54 (1H, s), 8.41 (1H, d, J= 2 Hz), 8.55 (1H, d, J= 2 Hz). MS (ESI"): m/z 443, MS (ESI+): m/z 445. Example 375 5-[2-[(benzoylamino)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3- yljpentanoic acid 1H NMR (CDCI3) 6 1.42 (3H, t, J= 7 Hz), 1.50-1.68 (4H, m), 2.25 (2H, t, J= 7 Hz), 2.44 (3H, s), 2.40-2.60 (2H, m), 3.07 (2H, q, J= 7 Hz), 4.89 (2H, m), 5.95 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.46-7.60 (4H, m), 7.83 (1H, br), 7.93 (2H, d, J= 8 Hz), 8.44 (1H, d, J= 2 Hz), 8.56 (1H, d, J= 2 Hz). MS (ESI"): m/z 469, MS (ESI+): m/z 471. Example 376 5-(7-ethyl-4-(5-melhyl-3-pyridiny])-2-{[(2-pyraz-b]pyridazin-3-yl)pentanoic acid 1H NMR (CDCI3) 5 1.41 (3H, I, J= 7 Hz), 1.51-1.72 (4H, m), 2.24 (2H, t, J= 7 Hz), 2.44 (3H, s), 2.45-2.58 (2H, m), 3.10 (2H, q, J= 7 Hz), 4.90 (2H, m), 5.94 (1H, d, J= 4 Hz), 6.59 (1H, d, J= 4 Hz), 7.55 (1H, s), 8.43 (1H, s), 8.53 (1H, s), 8.62 (1H, m), 8.79 (1H, d, J= 2 Hz), 9.20 (1H, br), 9.45 (1H, d, J= 2 Hz). MS (ES1+): m/z 471, MS (ESI+): m/z 473. Example 377 5-[7-ethyl-2-{[(methoxycarbonyl)amino]methyl}-4-(5-methyl-3-pyridinyl)pyrrolo[l,2- b]pyridazin-3-yl]pentanoic acid 1H NMR (CDCI3) 6 1.38 (3H, t, J= 7 Hz), 1.45-1.65 (4H, m), 2.23 (2H, t, J= 7 Hz), 2.40-2.53 (2H, m), 2.44 (3H, s), 3.02 (2H, q, J= 7 Hz), 3.05 (3H, s), 4.58 (2H, s), 5.69 (1H, br), 5.96 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.53 (1H, s), 8.41 (1H, d, J= 2 Hz), 8.54 (1H, d, J= 2 Hz). Example 378 To a solution of ethyl 7-ethyl-2-methyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazine-3-carboxylate (682 mg) in ethanol (20 mL) was added potassium hydroxide (5 g) solution (10 mL) and the mixture was heated under reflux for 1 hour. The solution was acidified with 1 N hydrochloric acid to pH 3-4 and diluted with brine, and extracted with chloroform twice. The organic layer was separated, dried over magnesium sulfate, and evaporated in vacuo. The crude produt was triturated with ethyl acetate to give 7-ethyl-2-methyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazine-3-carboxylic acid as a yellow powder (590 mg) 7-ethyl-2-methyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazine-3-carboxylicacid 1H NMR (CDCI3) 6 1.39 (3H, t, J= 7 Hz), 2.44 (3H, s), 2.69 (3H, s), 3.05 (2H, q, J= 7 Hz), 6.29 (1H, d, J= 4 Hz), 6.67 (1H, d, J= 4 Hz), 7.97 (1H, s), 8.41 (1H, s), 8.58 (lH,s). MS (ESO: m/z 294 , MS (ES1+): m/z 296. The following compound(s) was(were) obtained in substantially the same manner as that of Example 175. Example 379 5-[4-(3-cyanophenyl)-2-(ethoxymethyl)-7-ethylpyrrolo[lJ2-b]pyridazin-3-yl]pentanoic acid 1HNMR(CDCl3)61.25(3H3t3J = 7Hz),134-1.53(7H,m)>2.2()(2H,tJJ = 7Hz), 2.53 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.62 (2H, q, J = 7 Hz), 4.66 (2H, s), 5.33 (1H, d, J = 5 Hz), 6,57 (1H, d, J = 5 Hz), 7.60 (2H, m), 7.66 (1H, s), 7.74 (1H, m) Example 380 5-[2-[(benzyloxy)methyl]-4-(3-cyanophenyl)-7-ethylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid 1H NMR (CDC13) 6 1.30-1.46 (7H, m), 2.11 (2H, t, J = 7 Hz), 2.50 (2H, rn), 3.02 (2H, q, J = 7 Hz), 4.64 (3H, s), 4.71 (3H, s), 5.83 (1H, d, J = 5 Hz), 6.56 (1H, d, J = 5 Hz), 7.25-7.34 (5H, m), 7.57 (2H, d, J = 9 Hz), 7.65 (1H, s), 7.74 (1H, m). MS (ESI+): m/z 468 (M + H) Example 381 4-({[3-(4-carboxybutyl)-4-(3-cyanophenyl)-7-ethylpyrrolo[l,2-b]pyridazin-2-yl]methoxy}methyl)benzoic acid 1H-NMR (CDC13) 6 1.05-1.43 (7H, m), 1.92 (2H, m), 2.31 (2H, m), 3.04 (2H, m), 4.65 (2H, s), 4.72 (2H, s), 5.82 (1H, m), 6.58 (1H, m), 7.46-7.77 (6H, m), 8.09 (2H,d,J = 8Hz). MS(ESI+):m/z510(M-H) Example 381-2 4-({[4-[3-(carbamoyl)phenyl]-3-(4-carboxybutyl)-7-ethylpyrrolo[l,2-b]pyridazin-2-yl]methoxy}methyl)benzoic acid 1H-NMR (CDCI3) 8 1.20-1.45 (7H, m), 2.03 (2H, m), 2.52 (2H, m), 3.03 (2H, q, J = 7 Hz), 4.69 (2H, s), 4.73 (2H, s), 5.36 (1H, d, J = 5 Hz), 6.57 (1H, d, J = 5 Hz), 7.39-7.60 (4H, m), 7.77 (1H, s), 7.93 (1H, d, J = 8 Hz), 7.98 (2H, d,J = 8 Hz). MS(ESI+):m/z528(M-H) The following compound(s) was(were) obtained in substantially the same manner as that of Example 77. Example 382 5-{4-(5-bromo-3-pyridinyl)-7-ethyl-2-[(4-m-b]pyridazin-3-yl}pentanoic acid 1H NMR (CDCb) 6 1.34 (3H, t, J = 7 Hz),1.38-1.59 (4H, m), 2.22 (2H, m), 2.43-2.60 (5H, m), 2.83-3.04 (8H, m), 3.74 (3H, s),5.88 (1H, d, J = 5 Hz), 6.56 (1H, d, J = 5 Hz), 7.87 (1H, m), 8.54 (1H, m), 8.76 (1H, m). Example 383 5-[4-(5-bromo-3-pyridinyl)-2-(cyanomethyl)-7-ethylpyrrolo[l,2-b]pyridazin-3-yljpentanoic acid 1H NMR (CDCb) 5 1.35-1.60 (7H, m), 2.27 (2H, m), 2.46 (2H, m), 3.03 (2H, q, J = 7 Hz), 3.98 (2H, s), 3.97 (1H, d, J = 5 Hz), 6.65 (1H, d, J = 5 Hz), 7.90 (1H, m), 8.54 (lH,s,br), 8.79 (lH,s,br). Example 384 5-[4-(5-brorno-3-pyridinyl)-7-ethyl-2-(hydroxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid 1H NMR (CDCb) 5 1.35-1.60 (7H, m), 2.22 (2H, t, J = 7 Hz), 2.38 (2H, m), 3.02 (2H, q, J = 7 Hz), 4.86 (2H, s), 5.95 (1H, d, J = 5 Hz), 6.60 (1H, d, J = 5 Hz), 7.88 (1H, m), 8.54 (1H, s, br), 8.79 (1H, s, br). Example 385 To a solution of 7-ethyl-2-methyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazine-3-carboxylic acid (70 mg), l-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (68.2 mg) and 1-hydroxybenotriazole (48 mg) in dimethylformamide (2 mL) was added 2-aminoethanoI (17.4 mg) and the mixture was stirred at ambient temperature for 1 hour. The mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with saturated sodium bicarbonate solution, water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of chloroform and methanol (50:1 - 10:1). The crude product was triturated with isopropylether to give 7-ethyl-N-(2-hydroxyethyl)-2-methyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazine- 3-carboxamide as a yellow powder (47 mg). 7-ethyl-N-(2-hydroxyethyl)-2-methyl-4-(5-melhyl-3-pyridinyl)pyrrolo[l32-b] 3-carboxamide 1H NMR (CDCb) 6 1.38 (3H, t, J= 7 Hz), 2.39 (3H, s), 2.57 (3H, s), 3.02 (2H, q, J= 7 Hz), 3.33 (2H, m), 3.45 (2H, m), 6.03 (1H, br), 6.31 (1H, d, J= 4 Hz), 6.66 (1H, d, J= 4 Hz), 7.71 (1H, s), 8.47 (1H, s), 8.58 (1H, s). MS (ESI): m/z 337, MS (ESI+): m/z 339. The following compound(s) was(were) obtained in substantially the same manner as that of Example 385. Example 386 N-butyl-7-ethyl-2-methyl-4-(5"methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazine-3-carboxamide 1H NMR (CDCI3) 8 0.80 (3H, t, J= 7 Hz), 0.96-1.08 (2H, m), 1.08-1.25 (2H, m), 1.38 (3H, t, J= 7 Hz), 2.40 (3H, s), 2.56 (3H, s), 3.03 (2H, q, J= 7 Hz), 3.16 (2H, m), 5.36 (1H, br), 6.31 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.69 (1H, s), 8.53 (1H, s),8.62(lH,s). MS(ESl+):m/z351. Example 387 ethyl 3-({[7-ethyl-2-methyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3- yl]carbonyl}amino)propanoate 1HNMR (CDCI3) 5 1.24 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 2.21 (2H, t, J= 7 Hz), 2.40 (3H, s), 2.55 (3H, s), 3.03 (2H, q, J= 7 Hz), 3.43 (2H, q, J= 7 Hz), 4.04 (2H, q, J= 7 Hz), 6.08 (1H, br), 6.30 (1H, d, J= 4 Hz), 6.65 (1H, d, J= 4 Hz), 7.67 (1H, • s), 8.50 (1H, d, J= 1 Hz), 8.60 (1H, d, J= 1 Hz). MS(ESl+):m/z395. The following compound(s) was(were) obtained in substantially the same manner as that of Preparation 176. Example 388 4-(5-bromo-3-pyridinyl)-7-ethyl-2-methyl-3-[3-(4-morpholinyl)-3-oxopropyl]pyrrolo[l,2- b]pyridazine 1H NMR(CDC13) 5:1H NMR(CDC13) 6:1.37(3H, t, J=7Hz), 2.41(2H, t, J=7Hz), 2.60(3H, s), 2.72-2.82(2H, m), 3.01(2H, q, J=7Hz), 3.19(2H, t, J=5Hz), 3.55(4H, t, J=5Hz), 3.63(2H, t, J=5Hz), 5.89(1H, d, J=4Hz), 6.55(1H, d, J=4Hz), 7.87(1H, t, J=lHz), 8.54(1H, d, J=lHz), 8.77(1H, d, J=lHz) MS(m/z) 457(M+), 459(M++2), 115(bp) mp. 178-180°C Example 389 3-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]-N- tnethylpropanamide 1H NMR(CDC13) 6:1H NMR(CDC13) 5:1.38(3H, t, J=7Hz), 2.20(2H, t, J=7Hz), 2.60(3H, s), 2.75(3H, d, J=6Hz), 2.78-2.89(2H, m), 3.01(2H, q, J=7Hz), 5.21-5.27(1H, m), 5.88(1H, d, J=4Hz), 6.54(1H, d, J=4Hz), 7.86(1H, t, J=lHz), 8.53(1H, d, J=lHz), 8.78(1H, d, J=lHz) MS(m/z) 401(M++1),403(M++1), 115(bp) mp. 172-174- The following compound(s) was(were) obtained in substantially the same manner as that of Example 263. Example 390 N-{3-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-y]]propanoyl}methanesulfonamide 1H NMR(CDC13) 6:1.36(3H, t, J=7Hz), 2.33-2.45(2H, m), 2.58(3H, s), 2.84-2.95(2H, m), 3.01(2H, q, J=7Hz), 3.26(3H,s), 5.89(1H, d, J=4Hz), 6.56(1H, d, J=4Hz), 7.90(1H, s), 8.50(1H, s), 8.77(1H, s) MS(m/z) 465(M+, bp), 467(M+-2, bp) mp. 196.5-197.5r The following compound(s) was(were) obtained in substantially the same manner as that of Example 224. Example 391 2-[{3-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrit>lo[l,2-b]pyridazin-3-yl]propanoyl}(methyl)amino]ethanesulfonic acid 1H NMR (CDCJ3) 6 1.32 (3H, t, J = 7 Hz), 1.90 2H, m), 2.26 (3H, s), 2.57-2.2.78 (4H, m), 2.98 (2H, q, J = 7 Hz), 3.31 (2H, m), 6.00 (1H, d, J = 5 Hz), 6.61 (1H, d, J = 5 Hz), 7.20-7.52 (5H,m). The following compound(s) was(were) obtained in a similar manner to that of Preparation 20. Preparation 217 1-tert-butyl 7-ethyl 2-(isobutoxyacetyl)heptanedioate 1H NMR (300 MHz, CDC13) 6 0.95 (6H, d, J = 7 Hz), 1.27 (3H, t, J = 7 Hz), 1.31-1.41 (2H, m), 1.46 (9H, s), 1.66 (2H, tt, J = 7,7 Hz), 1.75-1.98 (3H, m), 2.31 (2H, t, J = 8 Hz), 3.26 (2H, d, J = 7 Hz), 3.56 (1H, t, J = 7 Hz), 4.06-4.17 (4H, m). Preparation 218 1-tert-butyl 6-ethyl 2-(isobutoxyacetyl)hexanedioate 1H NMR (300 MHz, CDC13) 5 0.93 (6H, d, J = 7 Hz), 1.25 (3H, t, J = 7 Hz), 1.45 (9H, s), 1.59-1.69 (2H, m), 1.80-1.95 (3H, m), 2.32 (2H, t, J = 7 Hz), 2.25 (2H, d, J = 7 Hz), 3.57 (1H, t, J = 7 Hz), 4.10 (2H, s), 4.12 (2H, q, J = 7 Hz). The following compound(s) was(were) obtained in a similar manner to that of Preparation 24. Preparation 219 1 -tert-butyl 6-ethyl 2-acetyl-2-(2-chloroisonicotinoyl)hexanedioate 1H NMR (CDCI3) 6 1.26 (3H, t, J= 7 Hz), 1.34 (9H, s), 1.60-1.73 (2H, m), 2.22-2.32 (2H, m), 2.39 (2H, t, J= 7 Hz), 2.49 (3H, s), 4.12 (2H, q, J= 7 Hz), 7.43 (1H, d, J= 5 Hz), 7.57 (1H, s), 8.50 (1H, d, J= 5 Hz). MS (ESI+): m/z 412. Preparation 220 1 -tert-butyl 5-ethyl 2-acetyl-2-(2-chloroisonicotinoyl)pentanedioate 1H NMR (CDCI3) 6 1.37 (3H, t, J= 7 Hz), 1.72-1.84 (2H, m), 2.33 (2H, t, J= 7 Hz), 2.47-2.57 (2H, m), 2.58 (3H, s), 3.03 (2H, q, J= 7 Hz), 5.88 (1H, d, J= 4 Hz), 6.53 (1H, d, J= 4 Hz), 7.27 (1H, m), 7.38 (1H, s), 8.53 (1H, d, J= 5 Hz). MS (ESI"): m/z 356, MS (ES1+): m/z 358. Preparation 221 1 -tert-buty) 7-ethyl 2-(2-chloroisonicotinoyl)-2-(phenylacetyl)heptanedioate 1H NMR (CDC13) 5 1.24 (3H, t, J= 7 Hz), 1.35 (9H, s), 1.63-1.76 (2H, m), 2.22-2.37 (4H, m), 3.93 (1H, d, J= 17 Hz), 4.12 (2H, q, J= 7 Hz), 4.29 (1H, d, J= 17 Hz), 7.22 (2H, d, J= 8 Hz), 7.26-7.36 (4H, m), 7.50 (1H, s), 8.42 (1H, d, J= 5 Hz). MS (ESI+): m/z 502. Preparation 222 tert-buty] 2-[2-(2-methoxy-2-oxoethoxy)ethyl]-2-[(5-methyl-3-pyridinyl)carbonyl]-3- oxobutanoate 1H NMR (CDCI3) 6 1.33 (9H, s), 2.39 (3H, s), 2.47 (3H, s), 2.62 (2H, t, J= 7 Hz), 3.66 (2H, m), 3.70 (3H, s), 3.90 (2H, s), 7.87 (1H, s), 8.56 (1H, s), 8.75 (1H, s). MS (ESI+): m/z 394. Preparation 223 1-tert-butyl 4-ethyl 2-acetyl-2-[(5-bromo-3-pyridinyl)carbonyl]succinate 1H NMR (CDCI3) 6 1.27 (3H, t, J= 7 Hz), 1.41 (9H, s), 2.45 (3H, s), 3.22 (2H, m), 4.12 (2H, q, J= 7 Hz), 8.22 (1H, m), 8.80 (1H, m), 8.82 (1H, m). MS (ES1+): m/z 428 430. Preparation 224 1-tert-butyl 5-ethyl 2-[(acetyloxy)acetyl]-2-[(5-methyl-3- pyridinyl)carbonyl]pentanedioate 1H NMR (CDC13) 6 1.23 (3H, t, J= 7 Hz), 1.35 (9H, s), 2.14 (3H, s), 2.40 (3H, s), 2.40-2.48 (2H, m), 2.62-2.70 (2H, m), 4.12 (2H, q, J= 7 Hz), 5.12 (1H, d, J= 18 Hz), 5.34 (1H, d, J= 18 Hz), 7.85 (1H, s), 8.58 (1H, s), 8.78 (1H, s). MS (ESI+): m/z 436. Preparation 225 1-tert-butyl 6-ethyl 2-[(acetyloxy)acetyl]-2-[(5-methyl-3-pyridiny])carbonyl1Hexanedioate 1H NMR (CDC13) 5 1.24 (3H, t, J= 7 Hz), 1.34 (9H, s), 1.60-1.75 (2H, m), 2.14 (3H, s), 2.26-2.39 (4H, m), 2.40 (3H, s), 4.12 (2H, q, J= 7 Hz), 5.13 (1H, d, J= 18 Hz), 5.40 (1H, d, J= 18 Hz), 7.86 (1H, s), 8.57 (1H, s), 8.78 (1H, s). MS (ESI+): m/z 450. 'reparation 226 -tert-butyl 7-elhyl 2-[(acetyloxy)acetyl]-2-(3-cyanobenzoyl)heptanedioate - NMR (CDC13) 6 1.24 (3H, t, J= 7 Hz), 1.32 (9H, s), 1.26-1.46 (2H, m), 1.66-1.77 (2H, m), 2.14 (3H, s), 2.26-2.38 (4H, m), 4.12 (2H, q, J= 7 Hz), 5.06 (1H, d, J= 18 Hz), 5.42 (1H, d, J= 18 Hz), 7.57 (1H, t, J= 8 Hz), 7.81 (1H, d, J= 8 Hz), 7.92 (lH,d,J=8Hz),8.09(lH,s). Preparation 227 1-tert-butyl 6-ethyl 2-[(acetyloxy)acetyl]-2-[(5-bromo-3-pyridinyl)carbonyl1Hexanedioate 1H NMR (CDCI3) 0 1.25 (3H, t, J= 7 Hz), 1.36 (9H, s), 1.60-1.74 (2H, m), 1.85-1.96 (2H, m), 2.14 (3H, s), 2.28-2.42 (2H, m), 4.12 (2H, q, J= 7 Hz), 5.12 (1H, d, J= 17 Hz), 5.42 (1H, d, J= 17 Hz), 8.23 (1H, m), 8.81 (1H, m), 8.83 (1H, m). Preparation 228 1-tert-butyl 5-ethyl 2-[(acetyloxy)acetyl]-2-[(5-bromo-3-pyridinyl)carbonyl]pentanedioate 1H NMR (CDCI3) 6 1.25 (3H, t, J= 7 Hz), 1.37 (9H, s), 2.14 (3H, s), 2.41-2.51 (2H, m), 2.66 (2H, t, J= 7 Hz), 4.13 (2H, q, J= 7 Hz), 5.11 (1H, d, J= 18 Hz), 5.33 (1H, d, J= 18 Hz), 8.22 (1H, m), 8.82 (2H, m). MS (ES1+): m/z 500 502. Preparation 229 1-tert-butyl 5-ethyl 2-[(cyclohexylmethoxy)acetyl]-2-[(5-methyl-3- pyridinyl)carbonyl]pentanedioate 1H NMR (CDC13) 5 0.80-0.98 (2H, m), 1.00-1.32 (3H,m), 1.23 (3H, t, J= 7 Hz), 1.38 (9H, s), 1.46-1.62 (6H, m), 2.39 (3H, s), 2.40-2.72 (4H, m), 3.19 (2H, d, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 4.31 (1H, d, J= 17 Hz), 4.39 (1H, d, J= 17 Hz), 7.88 (1H, s), 8.56 (lH,s), 8.77 (lH,s). MS(ESl+):m/z490. Preparation 230 1-tert-buty] 5-ethyl 2-[(5-bromo-3-pyridinyl)carbonyl]-2- [(cyclohexylmethoxy)acetyl]pentanedioate 1H NMR (CDC13) 5 0.78-0.98 (2H, m), 1.10-1.33 (3H, m), 1.25 (3H,1, J= 7 Hz), 1.40 (9H, s), 1.38-1.83 (6H, m), 2.35-2.75 (4H, m), 3.22 (2H, d, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 4.25 (1H, d, J= 17 Hz), 4.37 (1H, d, J= 17 Hz), 8.22 (1H, s), 8.78 (1H, s),8.86(lH,s). MS(ESl+):m/z554 556. Preparation 231 1-tert-butyl 6-ethyl 2-[(5-bromo-3-pyridinyl)carbonyl]-2- [(cyclohexylmethoxy)acetyl1Hexanedioate 1H NMR (CDCI3) 6 0.80-0.97 (2H, m), 1.12-1.35 (3H, m), 1.25 (3H, t, J= 7 Hz), 1.39 (9H, s), 1.46-1.80 (10H, m), 2.22-2.45 (2H,m), 3.20 (2H, d, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 4.30 (1H, d, J= 17 Hz), 4.38 (1H, d, J= 17 Hz), 8.22 (1H, s), 8.78 (1H, s),8.85(lH,s). MS(ESl+):m/z568 570. Preparation 232 1-tert-butyl 6-ethyl 2-[(cyclopropylmethoxy)acetyl]-2-[(5-methyl-3- pyridinyl)carbonyl1Hexanedioate 1H NMR (CDCI3) 6 0.16-0.28 (2H, m), 0.48-0.59 (2H, m), 0.98-1.12 (1H, m), 1.24 (3H, t, J= 7 Hz), 1.37 (9H, s), 1.55-1.80 (4H, m), 2.18-2.40 (2H, m), 2.39 (3H, s), 3.31 (2H, m), 4.12 (2H, q, J= 7 Hz), 4.38 (1H, d, J= 17 Hz), 4.53 (1H, d, J= 17 Hz), 7.88 (1H, s), 8.55 (1H, d, J= 2 Hz), 8.75 (1H, d, J= 2 Hz). MS(ESl+):m/z462. Preparation 233 1-tert-butyl 5-ethyl 2-[(cyclopropy]methoxy)acetyl]-2-[(5-methyl-3- pyridinyl)carbonyl]pentanedioate 1H NMR (CDCI3) 6 0.15-0.23 (2H, m), 0.48-0.56 (2H, m), 0.95-1.10 (1H, m), 1.24 (3H, t, J= 7 Hz), 1.39 (9H, s), 2.39 (3H, s), 2.40-2.68 (4H, m), 3.28 (2H, m), 4.12 (2H, q, J= 7 Hz), 4.36 (1H, d, J= 17 Hz), 4.48 (1H, d, J= 17 Hz), 7.88 (1H, s), 8.55 (1H, s), 8.75 (lH,s). MS(ESl+):m/z448. Preparation 234 1-tert-butyl 5-ethyl 2-[(5-bromo-3-pyridinyl)carbonyl]-2-[(2- methoxyethoxy)acetyl]pentanedioate 1H NMR (CDC13) 5 1.26 (3H, t, J= 7 Hz), 1.46 (9H, s), 2.15-2.25 (2H, m), 2.42-2.72 (2H, m), 3.38 (3H, s), 3.48-3.72 (4H, m), 4.12 (2H, q, J= 7 Hz), 4.43 (1H, d, J= 17 Hz), 4.58 (1H, d, J= 17 Hz), 8.22 (1H, s), 8.78 (1H, s), 8.82 (1H, s). MS(ES1+):m/z516 518. Preparation 235 tert-butyl 2-[(5-bromo-3-pyridinyl)carbonyl]-3-oxobutanoate 1H NMR (CDCI3) 6 1.22,1.30 (9H, s), 2.22,2.45 (3H, s), 7.96, 8.13 (1H, s), 8.66, 8.76-8.80 (2H,m). Preparation 236 1-tert-butyl 6-ethyl 2-[(acetyloxy)acetyl]-2-[(5-chloro-3-pyridinyl)carbonyl1Hexanedioate 1H NMR (300 MHz, CDCI3) 5 1.25 (3H, t, J = 7 Hz), 1.36 (9H, s), 1.63-1.71 (2H, m), 2.14 (3H, s), 2.27-2.40 (4H, m), 4.13 (2H, q, J = 7 Hz), 5.11 (1H, d, J = 18 Hz), 5.38 (1H, d, J = 18 Hz), 8.07 (1H, dd, J = 2 Hz), 8.71 (1H, d, J = 2 Hz), 8.80 (1H, d,J = 2Hz). Preparation 237 1-tert-butyl 7-ethyl 2-[(5-chloro-3-pyridinyl)carbonyl]-2- [(cyclopropylmethoxy)acetyl1Heptanedioate 1H NMR (300 MHz, CDC13) 8 0.15-0.20 (2H, m), 0.49-0.58 (2H, m), 0.95-1.04 (1H, m), 1.24 (3H, t, J = 7 Hz), 1.38 (9H, s), 1.68 (2H, tt, J = 7,7 Hz), 2.14-2.33 (4H, m), 3.26-3.29 (2H, m), 4.07-4.19 (4H, m), 4.31 (1H, d, J = 17 Hz), 4.45 (1H, d, J = 17 Hz), 8.05 (1H, dd, J = 2 Hz), 8.68 (1H, d, J = 2 Hz), 8.78 (1H, d, J = 2 Hz). Preparation 238 1-lert-butyl 6-ethyl 2-[(5-chloro-3-pyridinyl)carbonyl]-2- [(cyclopropy]methoxy)acetyl1Hexanedioate !H NMR (300 MHz, CDC13) 6 0.14-0.21 (2H, m), 0.49-0.55 (2H, m), 0.92-1.04 (1H, m), 1.25 (3H, t, J = 7 Hz), 1.39 (9H, s), 1.62-1.74 (2H, m), 1.82-1.90 (2H, m), 2.21-2.33 (2H, m), 3.27-3.31 (2H, m), 4.12 (2H, q, J = 7 Hz), 4.34 (1H, d, J = 18 Hz), 4.46 (1H, d, J = 18 Hz), 8.07 (1H, dd, J = 2,2 Hz), 8.68 (1H, d, J = 2 Hz), 8.80(lH,d,J = 2Hz). Preparation 239 1-tert-butyl 7-ethyl 2-[(5-bromo-3-pyridinyl)carbonyl]-2-(isobutoxyacetyl)heptanedioate 1H NMR (300 MHz, CDCI3) 6 0.85 (6H, d, J = 7 Hz), 1.24 (3H, t, J = 7 Hz), 1.38 (9H, s), 1.67 (2H, t, J = 7 Hz), 1.75-1.93 (3H, m), 2.24-2.33 (4H, m), 3.17 (2H, d, J = 7 Hz), 4.11 (2H, q, J = 7 Hz), 4.28 (1H, d, J = 17 Hz), 4.38 (1H, d, J = 17 Hz), 8.20 (1H, dd, J = 2, 2 Hz), 8.79 (1H, d, J = 2 Hz), 8.84 (1H, d, J = 2 Hz). Preparation 240 1-tert-butyl 5-ethyl 2-[(5-chloro-3-pyridinyl)carbonyl]-2-(isobutoxyacetyl)pentanedioate 1H NMR (300 MHz, CDCI3) 6 0.84 (6H, d, J = 7 Hz), 1.24 (3H, t, J = 7 Hz), 1.39 (9H, s), 1.80 (1H, qt, J = 7 Hz), 2.34-2.71 (4H, m), 3.17 (2H, d, J = 7 Hz), 4.12 (2H, q, J = 7 Hz), 4.28 (1H, d, J = 18 Hz), 4.36 (1H, d, J = 18 Hz), 8.07 (1H, s), 8.69 (1H, s),8.83(lH,s). Preparation 241 1-tert-butyl 5-ethyl 2-[(acetyloxy)acetyl]-2-(3-chlorobenzoyl)pentanedioate 1H NMR (300 MHz, CDCI3) 8 1.24 (3H, t, J = 7 Hz), 1.34 (9H, s), 2.14 (3H, s), 2.35-2.44 (2H, m), 2.60-2.68 (2H, m), 4.11 (2H, q, J = 7 Hz), 5.11 (1H, d, J = 18 Hz), 5.35 (1H, d, J = 18 Hz), 7.38 (1H, dd, J = 8, 8 Hz), 7.53 (1H, d, J = 8 Hz), 7.60 (lH,d,J = 8Hz),7.79(lH,s). Preparation 242 1-tert-butyl 6-ethyl 2-[(5-bromo-3-pyridinyl)carbonyl]-2-(isobutoxyacetyl)hexanedioate 1H NMR (300 MHz, CDCI3) 5 0.85 (6H, d, J = 7 Hz), 1.25 (3H, t, J = 7 Hz), 1.39 (9H, s), 1.59-1.72 (2H, m), 1.80 (1H, qt, J = 7, 7Hz), 2.19-2.39 (4H, m), 3.18 (2H, d, J = 7 Hz), 4.12 (2H, q, J = 7 Hz), 4.31 (1H, d, J = 17 Hz), 4.40 (1H, d, J = 17 Hz), 8.22 (1H, dd, J = 2,2 Hz), 8.79 (1H, d, J = 2 Hz), 8.85 (1H, d, J = 2 Hz). Preparation 243 tert-butyl 3-(5-bromo-3-pyridinyl)-2-[(5-bromo-3-pyridinyl)carbonyl]-3-oxopropanoate 1H NMR (CDC13) 6 1.05 (9H, s), 7.86 (2H, s), 8.46 (2H, s), 8.61 (2H, s). MS (ESI): m/z 481483 485. Preparation 244 1-tert-butyl 6-ethyl 2-[(acetyloxy)acetyl]-2-(3-chlorobenzoyl)hexanedioate 1H NMR (CDC13) 6 1.24 (3H, t, J = 8 Hz), 1.33 (9H, s), 1.56-1.72 (2H, m), 2.15 (3H, s), 2.20-2.41 (4H, m), 4.11 (2H, q, J = 8 Hz), 5.13 (1H, d, J = 18 Hz), 5.40 (1H, d, J = 18 Hz), 7.38 (1H, t, J = 8 Hz), 7.52 (1H, br d, J = 8 Hz), 7.60 (1H, br d, J = 8 Hz),7.79(lH,brs). Preparation 245 1-tert-butyl 7-ethyl 2-(methoxyacetyl)-2-[(5-methoxy-3-pyridinyl)carbonyl1Heptanedioate 1HNMR (CDCI3) 5 1.23 (3H, t, J = 8 Hz), 1.27-1.43 (11H, m), 1.60-1.74 (2H, m), 2.15-2.34 (4H, m), 3.37 (3H, s), 3.90 (3H, s), 4.10 (2H, q, J = 8 Hz), 4.35 (1H, d, J = 18 Hz), 4.48 (1H, d, J = 18 Hz), 7.58 (1H, m), 8.43 (1H, d, J = 3 Hz), 8.50 (lH,d,J = lHz). MS (ESI4): m/z 452 (M + H). Preparation 246 1-tert-butyl 7-ethyl 2-acetyl-2-[(5-methoxy-3-pyridinyl)carbonyl1Heptanedioate 1H NMR (CDCI3) 5 1.24 (3H, t, J = 8 Hz), 1.27-1.40 (11H, m), 1.60-1.74 (2H, m), 2.15-2.34 (4H, m), 2.44 (3H, s), 3.89 (3H, s), 4.10 (2H, q, J = 8 Hz), 7.61 (1H, m), 8.43 (1H, d, J = 3 Hz), 8.49 (1H, d, J = 1 Hz). MS (ESI+): m/z 422 (M + H). Preparation 247 1-tert-butyl 5-ethyI 2-(methoxyacetyl)-2-[(5-rnethoxy-3-pyridinyl)carbonyl]pentanedioate 1H NMR (CDCI3) 6 1.24 (3H, t, J = 8 Hz), 1.38 (9H, s), 2.36-2.48 (2H, m), 2.53-2.67 (2H, m), 3.37 (3H, s), 3.90 (3H, s), 4.11 (2H, q, J = 8 Hz), 4.33 (1H, d, J = 18 Hz), 4.45 (1H, d, J = 18 Hz), 7.59 (1H, m), 8.43 (1H, d, J = 3 Hz), 8.51 (1H, d, J = 1 Hz). MS (ESI+): m/z 446 (M + + Na). Preparation 248 1 -tert-butyl 6-ethyl 2-(methoxyacetyl)-2-[(5-methoxy-3-pyridinyl)carbonyl1Hexanedioate 1H NMR (CDC13) 6 1.24 (3H, t, J = 8 Hz), 1.37 (9H, s), 1.52-1.75 (2H, m), 2.18-2.39 (4H, m), 3.38 (3H, s), 3.90 (3H, s), 4.11 (2H, q, J = 8 Hz), 4.37 (1H, d, J = 18 Hz), 4.51 (1H, d, J = 18 Hz), 7.60 (1H, m), 8.43 (1H, d, J = 3 Hz), 8.50 (1H, d, J = 1 Hz). MS (ESI+): m/z 438 (M + H). Preparation 249 1-tert-butyl 7-ethyl 2-(methoxyacetyl)-2-(5-pyrimidinylcarbonyl)heptanedioate 1H NMR (CDCI3) 6 1.24 (3H, t, J = 8 Hz), 1.30-1.44 (llH,m), 1.62-1.75 (2H,m), 2.16-2.35 (4H, m), 3.35 (3H, s), 4.11 (2H, q, J = 8 Hz), 4.20 (1H, d, J = 18 Hz), 4.33 (1H, d, J = 18 Hz), 9.01 (2H, s), 9.31 (1H, s). MS (ESI+): m/z 423 (M + H). Preparation 250 1-tert-butyl 6-ethyl 2-[(5-chloro-3-pyridinyl)carbonyl]-2-(rnethoxyacetyl)hexanedioate 1H NMR (CDCI3) 6 1.26 (3H, t, J = 8 Hz), 1.39 (9H, s), 1.57-1.74 (2H, m), 1.78 (2H, br t, J = 8 Hz), 2.23-2.41 (2H, m), 3.38 (3H, s), 4.14 (2H, q, J = 8 Hz), 4.33 (1H, d, J = 18 Hz), 4.45 (1H, d, J = 18 Hz), 8.07 (1H, m), 8.71 (1H, br s), 8.80 (1H, br s). MS(ES1+):m/z442(M + H). Preparation 251 1 -tert-butyl 5-ethyl 2-[(5-chloro-3-pyridinyl)carbonyl]-2-(methoxyacetyl)pentanedioate 1H NMR (CDCI3) 6 1.25 (3H, t, J = 8 Hz), 1.39 (9H, s), 2.37-2.48 (2H, m), 2.53-2.65 (2H, m), 3.36 (3H, s), 4.13 (2H, q, J = 8 Hz), 4.26 (1H, d, J = 18 Hz), 4.40 (1H, d, J = 18 Hz), 8.06 (1H, br s), 8.70 (1H, br s), 8.80 (1H, br s). MS(ESI+):m/z428(M + H). Preparation 252 1-tert-butyl 7-ethyl 2-[(5-chloro-3-pyridinyl)carbonyl]-2-(methoxyacety])heptaneclioate 1H NMR (CDCI3) 5 1.24 (3H, t, J = 8 Hz), 1.31-1.48 (11H, m), 1.55-1.75 (2H, m), 2.15-2.35 (4H, m), 3.36 (3H, s), 4.10 (2H, q, J = 8 Hz), 4.27 (1H, d, J = 18 Hz), 4.43 (1H, d, J = 18 Hz), 8.03 (1H, t, J = 2 Hz), 8.69 (1H, d, J = 2 Hz), 8.77 (1H, d, J = 2 Hz). MS (ESI+): m/z 456 (M + H). Preparation 253 methyl 4-(acetyloxy)-2-[(5-bromo-3-pyridinyl)carbonyl]-3-oxobutanoate 1HNMR (CDCI3) 6 2.21 (3H, s), 3.58 (3H, br s), 4.87 (1H, br s), 5.19 (2H, br s), 7.98 (1H, br s), 8.58 (1H, br s), 8.79 (1H, br s). MS (ES1+): m/z 358,360 (M + H). Preparation 254 tert-butyl 2-(2-{2-[2-(acetyloxy)ethoxy]ethoxy}ethyl)-2-[(5-methyl-3- pyridinyl)carbonyl]-3-oxobutanoate 1H-NMR (CDCI3) 6 1.32 (9H, s), 2.07 (3H, s), 2.38 (3H, s), 2.45 (3H, s), 2.57 (2H, t, J = 7 Hz), 3.43 (4H, m), 3.57 (4H, m), 4.16 (2H, m), 7.84 (1H, m), 8.53 (1H, m), 8.75 (lH,m). Preparation 255 1-tert-butyl 6-ethyl 2-[(5-bromo-3-pyridinyl)carbonyl]-2-(methoxyacetyl)hexanedioate H NMR (CDCI3) 6 1.26 (3H, t, J= 7 Hz), 1.39 (9H, s), 1.55-1.75 (2H, m), 2.23-2.45 (4H, m), 3.38 (3H, s), 4.12 (2H, q, J= 7 Hz), 4.34 (1H, d, J= 18 Hz), 4.47 (1H, d, J= 18 Hz), 8.22 (1H, m), 8.81 (1H, d, J= 2 Hz), 8.83 (1H, d, J= 2 Hz). MS (ES1+): m/z 486 488. Preparation 256 ethyl 2-(2-chloroisonicotinoyl)-3-oxobutanoate 1H NMR (CDCI3) 5 0.91-1.00 (3H, m), 2.24 (1.2H, s), 2.48 (1.8H, s), 4.02 (1.2H, q, J = 8 Hz), 4.10 (0.8H, q J = 8 Hz), 7.24 (0.6H, m), 7.39 (0.6H, s), 7.45 (0.4H, m), 7.54 (lH,s), 8.49 (lH,m). MS (ES1+): m/z 298 (M + H). The following compound(s) was(were) obtained in a similar manner to that of Preparation 78. Preparation 257 ethyl 5-(2-chloroisonicotinoyl)-6-oxoheptanoate 1H NMR (CDC1-0 5 1.25 (3H, t, J= 7 Hz), 1.60-1.73 (2H, m), 1.98-2.10 (2H, m), 2.20 (3H, s), 2.35 (2H, t, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 4.37 (1H, t, J= 7 Hz), 7.67 (1H, d, J= 5 Hz), 7.77 (1H, s), 8.59 (1H, d, J= 5 Hz). MS (ESI+): m/z 312 . Preparation 258 ethyl 4-(2-chloroisonicotinoyl)-5-oxohexanoate 1H NMR (CDC13) 5 1.26 (3H, t, J= 7 Hz), 2.21 (3H, s), 2.22-2.35 (2H, m), 2.36-2.47 (2H, m), 4.12 (2H, q, J= 7 Hz), 4.57 (1H, t, J= 7 Hz), 7.76 (1H, dd, J= 2 Hz, 5 Hz), 7.83 (1H, d, J= 2 Hz), 8.61 (1H, d, J= 5 Hz). MS (ES1+): m/z 298. Preparation 259 ethyl 6-(2-chloroisonicotinoyl)-7-oxo-8-phenyloctanoate 1H NMR (CDCI3) 6 1.24 (3H, t, J= 7 Hz), 1.20-1.38 (2H, m), 1.60-1.72 (2H, m), 1.95-2.06 (2H, m), 2.28 (2H, t, J= 7 Hz), 3.71 (1H, d, J= 17 Hz), 3.80 (1H, d, J= 17 Hz), 4.12 (2H, q, J= 7 Hz), 4.41 (1H, t, J= 7 Hz), 7.10 (2H, m), 7.20-7.33 (4H, m), 7.39 (1H, s), 8.42 (1H, d, J= 5 Hz). Preparation 260 methyl ({3-[(5-methyl-3-pyridinyl)carbonyl]-4-oxopentyl}oxy)acetate 1H NMR (CDCI3) o 2.23 (3H, s), 2.23-2.40 (2H,m), 2.44 (3H, s), 3.58 (2H, m), 3.71 (3H, s), 4.02 (2H, s), 4.89 (1H, t, J= 7 Hz), 8.12 (1H, s), 8.64 (1H, s), 9.07 (1H, s). MS (ESI+): m/z 294. Preparation 261 methyl (4-oxo-4-phenylbutoxy)acetate 1H NMR (CDCI3) 6 2.04-2.16 (2H, m), 3.15 (2H, t, J= 7 Hz), 3.64 (2H, t, J= 7 Hz), 3.73 (3H, s), 4.09 (2H, s), 7.46 (2H, t, J= 8 Hz), 7.56 (1H, t, J= 8 Hz), 7.99 (2H, cl, J= 8 Hz). MS(ES1+):m/z237. The following compound(s) was(were) obtained in a similar manner to that of Preparation 78. Preparation 262 ethyl 3-[(5-bromo-3-pyridinyl)carbonyl]-4-oxopentanoate 1H NMR (CDCI3) 8 1.24 (3H, t, J= 7 Hz), 2.22 (3H, s), 2.97-3.17 (2H, m), 4.12 (2H, q, J= 7 Hz), 4.91 (1H, m), 8.41 (1H, m), 8.88 (1H, m), 9.12 (1H, m). MS (ESI+): m/z 328 330. Preparation 263 ethyl 6-(acetyloxy)-4-[(5-methyl-3-pyridinyl)carbonyl]-5-oxohexanoate 1H NMR (CDCI3) 6 1.25 (3H, t, J= 7 Hz), 1.98 (3H, s), 2.23-2.34 (2H, m), 2.40-2.50 (2H, m), 2.45 (3H, s), 4.12 (2H, q, J= 7 Hz), 4.69 (2H, m), 4.82 (1H, t, J= 7 Hz), 8.14 (1H, s), 8.67 (1H, s), 9.07 (1H, s). MS(ESI+):m/z336. Preparation 264 ethyl 7-(acetyloxy)-5-[(5-methyl-3-pyridinyl)carbonyl]-6-oxoheptanoate 1H NMR (CDCI3) 6 1.25 (3H, t, J= 7 Hz), 1.60-1.80 (2H, m), 2.02 (3H, s), 1.97-2.13 (2H, m), 2.35 (2H, t, J= 7 Hz), 2.45 (3H, s), 4.12 (2H, q, J= 7 Hz), 4.56 (1H, t, J= 7 Hz), 4.69 (1H, d, J= 17 Hz), 4.78 (1H, d, J= 17 Hz), 8.06 (1H, s), 8.66 (1H, s), 9.00 (lH,s). MS (ESI+): m/z 350. Preparation 265 ethyl 8-(acetyloxy)-6-(3-cyanobenzoyl)-7-oxooctanoate 1H NMR (CDCI3) 0 1 -24 (3H, t, J= 7 Hz), 1.35-1.50 (2H, m), 1.60-1.78 (2H, m), 2.04 (3H, s), 2.00-2.12 (2H, m), 2.29 (2H, t, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 4.49 (1H, I, J= 7 Hz), 4.68 (1H, d, J= 17 Hz), 4.75 (1H, d, J= 17 Hz), 7.66 (1H, t, J= 8 Hz), 7.88 (1H, d, J= 8 Hz), 8.16 (1H, d, J= 8 Hz), 8.26 (1H, s). MS (ESP): m/z 372. Preparation 266 ethyl 7-(acetyloxy)-5-[(5-bromo-3-pyridinyl)carbonyl]-6-oxoheptanoate 1H NMR (CDC13) 5 1.25 (3H, t, J= 7 Hz), 1.60-1.82 (2H, m), 2.04 (3H, s), 2.03-2.15 (2H, m), 2.35 (2H, t, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 4.51 (1H, t, J= 7 Hz), 4.70 (1H, d, J= 17 Hz), 4.75 (1H, d, J= 17 Hz), 8.39 (1H, m), 8.88 (1H, s), 9.07 (1H, s). MS (ESI): m/z 414 416, MS (ESI+): m/z 414 416. Preparation 267 ethyl 6-(acetyloxy)-4-[(5-bromo-3-pyridinyl)carbonyl]-5-oxohexanoate 1H NMR (CDCI3) 6-1.26 (3H, t, J= 7 Hz), 2.00 (3H, s), 2.22-2.36 (2H, m), 2.43-2.53 (2H, m), 4.13 (2H, q, J= 7 Hz), 4.70 (2H, m), 4.80 (1H, t, J= 7 Hz), 8.48 (1H, s), 8.90 (lH,s), 9.19 (lH.s). MS (ESI+): m/z 400 402. Preparation 268 ethyl 6-(cyclohexylmethoxy)-4-[(5-methyl-3-pyridinyl)carbonyl]-5-oxohexanoate 1H NMR (CDCI3) 6 0.60-0.82 (2H, m), 0.93-1.10 (3H, m), 1.12-1.65 (6H, m), 1.25 (3H, t, J= 7 Hz), 2.07-2.17 (1H, m), 2.22-2.35 (1H, m), 2.42 (2H, m), 2.44 (3H, s), 3.05-3.23 (2H, m), 3.96 (2H, s), 4.12 (2H, q, J= 7 Hz), 4.92 (1H, m), 8.16 (1H, s), 8.66 (lH,s), 9.08 (lH,s). MS (ESI+): m/z 390. Preparation 269 ethyl 4-[(5-bromo-3-pyridinyl)carbonyl]-6-(cyclohexylmethoxy)-5-oxohexanoate 1H NMR (CDCI3) 6 0.63-0.84 (2H, m), 0.93-1.88 (3H, m), 1.25 (3H, t, J= 7 Hz), 1.35-1.90 (6H, m), 2.02-2.14 (1H, m), 2.20-2.36 (1H, m), 2.44 (2H, t, J= 7 Hz), 3.04-3.20 (2H, m), 3.95 (2H, s), 4.13 (2H, q, J= 7 Hz), 4.85-4.93 (1H, m), 8.50 (1H, m), 8.88 (1H, d, J= 2 Hz), 9.20 (1H, d, J= 2 Hz). MS(ESl+):m/z454 456. Preparation 270 ethyl 5-[(5-bromo-3-pyridinyl)carbonyl]-7-(cyclohexylmethoxy)-6-oxoheptanoate 1H NMR (300 MHz, CDCI3) 6 0.75-0.86 (2H, m), 0.95-1.15 (3H, m), 1.24 (3H, t, J= 7 Hz), 1.40-1.90 (10H, m), 2.36 (2H, t, J= 7 Hz), 3.12 (2H, q, J= 7 Hz), 3.97 (2H, s), 4.12 (2H, q, J= 7 Hz), 4.71 (1H, t, J= 7 Hz), 8.41 (1H, s), 8.88 (1H, s), 9.12 (lH,s). MS(ES1+):m/z468 470. Preparation 271 ethyl 7-(cyclopropylmethoxy)-5-[(5-methyl-3-pyridinyl)carbonyl]-6-oxoheptanoate 1H NMR (CDC13) 6 -0.08-0.00 (1H, m), 0.00-0.15 (1H, m), 0.28-0.49 (2H, m), 0.72-0.87 (1H, m), 1.23 (3H, t, J= 7 Hz), 1.58-2.13 (4H, m), 2.32 (2H, t, J= 7 Hz), 2.44 (3H, s), 3.10-3.26 (2H, m), 4.02 (2H, m), 4.12 (2H, q, J= 7 Hz), 4.77 (1H, t, J= 7 Hz), 8.07 (1H, s), 8.63 (1H, s), 9.03 (1H, s). MS (ESI+): m/z 362. Preparation 272 ethyl 6-(cyclopropylmethoxy)-4-[(5-methyl-3-pyridinyl)carbonyl]-5-oxohexanoate 1H NMR (CDCI3) 6 -0.08-0.00 (1H, m), 0.00-0.13 (1H, m), 0.23-0.47 (2H, m), 0.68-0.84 (1H, m), 1.24 (3H, t, J= 7 Hz), 2.03-2.17 (1H, m), 2.22-2.36 (1H, m), 2.40 (2H, m), 2.44 (3H, s), 3.12 (2H, m), 3.98 (1H, d, J= 17 Hz), 4.06 (1H, d, J= 17 Hz), 4.12 (2H, q, J= 7 Hz), 4.93 (1H, m), 8.12 (1H, s), 8.65 (1H, s), 9.08 (1H, s). MS (ESI+): m/z 348. Preparation 273 ethyl 4-[(5-bromo-3-pyridinyl)carbonyl]-6-(2-methoxyethoxy)-5-oxohexanoate 1H NMR (CDCI3) 6 1.25 (3H, t, J= 7 Hz), 1.90-2.37 (2H, m), 2.43 (2H, t, J= 7 Hz), 3.18 (3H, s), 3.16-3.73 (4H, m), 4.06 (2H, q, J= 7 Hz), 4.10-4.24 (2H, m), 4.86-4.93 (1H, m), 8.51 (1H, m), 8.87 (1H, d, J= 2 Hz), 9.20 (1H, d, J= 2 Hz). MS (EST): m/z 414 416, MS (ESI+): m/z 416 418. Preparation 274 l-(5-bromo-3-pyridinyl)-l,3-butanedione 1H NMR (CDCI3) 6 2.25 (3H, s), 6.18 (1H, s), 8.31 (1H, s), 8.78 (1H, s), 8.96 (1H, s). MS(ESI+):m/z242 244. Preparation 275 ethyl 7-(acetyloxy)-5-[(5-chloro-3-pyridinyl)carbonyl]-6-oxoheptanoate 1H NMR (300 MHz, CDC13) 6 1.25 (3H, t, J = 7 Hz), 1.60-1.70 (4H, m), 2.04 (3H, s), 2.35 (2H, t, J = 6 Hz), 4.12 (2H, q, J = 7 Hz), 4.52 (1H, t, J = 7 Hz), 4.69 (1H, d, J = 18 Hz), 4.78 (1H, d, J = 18 Hz), 8.24 (1H, s), 8.78 (1H, s), 9.05 (1H, s). Preparation 276 ethyl 6-[(5-chloro-3-pyridinyl)carbonyl]-8-(cyclopropylmethoxy)-7-oxooctanoate 1H NMR (300 MHz, CDCI3) 5 -0.09-0.11 (2H, m), 0.25-0.35 (1H, m), 0.37-0.46 (1H, m), 0.70-0.79 (1H, m), 1.24 (3H, t, J = 7 Hz), 1.29-1.41 (2H, m), 1.64 (2H, t, J = 7 Hz), 1.72-1.84 (1H, m), 1.96-2.08 (1H, m), 2.28 (2H, t, J = 7 Hz), 3.12 (1H, dd, J = 10,7 Hz), 3.21 (1H, dd, J = 10,7 Hz), 3.97 (1H, d, J = 12 Hz), 4.05 (1H, d, J = 12 Hz), 4.11 (2H, q, J = 7 Hz), 4.70 (1H, t, J = 7 Hz), 8.26 (1H, dd, J = 2, 2 Hz), 8.77 (1H, dd, J = 2 Hz), 9.09 (1H, dd, J = 2 Hz). Preparation 277 ethyl 5-[(5-chloro-3-pyridinyl)carbonyl]-7-(cyclopropylmethoxy)-6-oxoheptanoate 1H NMR (300 MHz, CDCI3) 8 -0.07-0.09 (2H, m), 0.24-0.46 (2H, m), 0.68-0.79 (1H, m), 1.23 (3H, t, J = 7 Hz), 1.47-1.84 (3H, m), 1.98-2.10 (1H, m), 2.33 (2H, t, J = 7 Hz), 3.12 (1H, dd, J = 10,7 Hz), 3.21 (1H, dd, J = 10,7 Hz), 3.97 (1H, d, J = 17 Hz), 4.06 (1H, d, J = 17 Hz), 4.10 (2H, q, J = 7 Hz), 4.73 (1H, t, J = 6 Hz), 8.27 (1H, dd, J = 2,2 Hz), 8.77 (1H, d, J = 2 Hz), 9.10 (1H, d, J = 2 Hz). Preparation 278 ethyl 6-[(5-bromo-3-pyridinyl)carbonyl]-8-isobutoxy-7-oxooctanoate 1H NMR (300 MHz, CDCI3) 6 0.72 (3H, d, J = 7 Hz), 0.77 (3H, d, J = 7 Hz), 1.24 (3H, t, J = 7 Hz), 1.30-1.42 (2H, m), 1.54-1.70 (3H, m), 1.75-1.87 (1H, m), 1.95-2.08 (1H, m), 2.28 (2H, t, J = 8 Hz), 3.10 (1H, dd, J = 9,7 Hz), 3.14 (1H, dd, J = 9,7 Hz), 3.98 (2H, s), 4.11 (2H, q, J = 7 Hz), 4.70 (1H, t, J = 6 Hz), 8.39 (1H, dd, J = 2 Hz), 8.87 (1H, d, J = 2 Hz), 9.08 (1H, d, J = 2 Hz). Preparation 279 ethy] 4-[(5-chloro-3-pyridiny])carbonyl]-6-isobutoxy-5-oxohexanoale 1H NMR (300 MHz, CDC13) 6 0.68 (3H, d, J = 7 Hz), 0.72 (3H, d, J = 7 Hz), 1.25 (3H, t, J = 7 Hz), 1.52 (1H, qt, J = 7, 7 Hz), 2.02-2.13 (1H, m), 2.20-2.32 (1H, m), 2.44 (2H, t, J = 7 Hz), 3.07 (1H, dd, J = 9,7 Hz), 3.12 (1H, dd, J = 9, 7 Hz), 3.98 (2H, s), 4.14 (2H, q, J = 7 Hz), 4.90 (1H, d, J = 9 Hz), 4.92 (1H, d, J = 9 Hz), 8.34 (1H, dd, J = 2 Hz), 8.78 (1H, d, J = 2 Hz), 9.15 (1H, d, J = 2 Hz). Preparation 280 ethyl 6-(acetyloxy)-4-(3-chlorobenzoyl)-5-oxohexanoate 1H NMR (300 MHz, CDC13) 6 1.26 (3H, t, J = 7 Hz), 1.95 (3H, s), 2.20-2.29 (2H, m), 2.41-2.47 (2H, m), 4.15 (2H, q, J = 7 Hz), 4.64 (1H, d, J = 17 Hz), 4.71 (1H, d, J = 17 Hz), 4.78 (1H, t, J = 6 Hz), 7.48 (1H, dd, J = 8, 8 Hz), 7.60 (1H, d, J = 8 Hz), 7.96 (1H, d, J = 8 Hz), 8.04 (1H, s). Preparation 281 ethyl 5-[(5-bromo-3-pyridinyl)carbonyl]-7-isobutoxy-6-oxoheptanoate 1H NMR (300 MHz, CDCI3) 6 0.72 (3H, d, J = 7 Hz), 0.77 (3H, d, J = 7 Hz), 1.23 (3H, t, J = 7 Hz), 1.61-1.73 (3H, m), 1.77-1.88 (1H, m), 1.98-2.10 (1H, m), 2.33 (2H, t, J = 7 Hz), 3.10 (1H, dd, J = 9,7 Hz), 3.15 (1H, dd, J = 9, 7 Hz), 3.99 (2H, s), 4.11 (2H, q, J = 7 Hz), 4.73 (1H, t, J = 7 Hz), 8.40 (1H, dd, J = 2,2 Hz), 8.87 (1H, d, J = 2 Hz), 9.10 (1H, d, J = 2 Hz). Preparation 282 1,3-bis(5-bromo-3-pyridinyl)-l ,3-propanedione 1H NMR (DMSO-d6) 5 7.60 (1H, s), 8.78 (2H, s), 8.88 (2H, s), 9.30 (2H, s). Preparation 283 ethyl 7-(acetyloxy)-5-(3-chlorobenzoyl)-6-oxoheptanoate 1H NMR (CDCI3) 0 1.24 (3H, t, J = 8 Hz), 1.57-1.75 (2H,m), 1.90-2.12 (5H,m), 2.34 (2H, t, J = 8 Hz), 4.11 (2H, q, J = 8 Hz), 4.52 (1H, t, J = 8 Hz), 4.71 (2H, q, J = 8 Hz), 4.65 (1H,d,J = 16 Hz), 4.75 (1H, d, J = 16 Hz), 7.43 (1 H, t, J = 8 Hz), 7.60 (1H, br d, J = 8 Hz), 7.84 (1H, br d, J = 8 Hz), 7.96 (1H, br s). Preparation 284 ethyl 8-methoxy-6-[(5-mcthoxy-3-pyridinyl)carbonyl]-7-oxooctanoate 1H NMR (CDCb) 6 1.23 (3H, t, J = 8 Hz), 1.27-1.43 (2H, m), 1.55-1.70 (2H, in), 1.84 (1H, m), 2.00 (1H,m), 2.27 (2H, d, J = 8 Hz), 3.26 (3H, s), 3.92 (3H, s), 3.98 (2H, d, J = 5 Hz), 4.10 (2H, q, J = 8 Hz), 4.67 (1H, t, J = 8 Hz), 7.71 (1H, m), 8.50 (1H, d, J = 3 Hz), 8.78 (1H, br s). MS(ESl+):m/z352(M + H). Preparation 285 ethyl 6-[(5-methoxy-3-pyridinyl)carbonyl]-7-oxooctanoate 1H NMR (CDC13) 5 1.24 (3H, t, J = 8 Hz), 1.27-1.41 (2H, m), 1.60-1.73 (2H, m), 1.90-2.14 (2H, m), 2.18 (3H, s), 2.24-2.84 (2H, m), 3.26 (3H, s), 3.92 (3H, s), 4.10 (2H, q, J = 8 Hz), 4.40 (1H, t, J = 8 Hz), 7.71 (1H, m), 8.51 (1H, d, J = 3 Hz), 8.78(lH,brs). Preparation 286 ethyl 6-methoxy-4-[(5-methoxy-3-pyridinyl)carbonyl]-5-oxohexanoate 1H NMR (CDC13) o 1.24 (3H, t, J = 8 Hz), 2.10 (1H, m), 2.25 (1H, m), 2.38-2.47 (2H, m), 3.24 (3H, s), 3.94 (3H, s), 3.95 (1H, d, J = 16 Hz), 4.00 (1H, d, J = 16 Hz), 4.12 (2H, q, J = 8 Hz), 4.38 (1H, m), 7.83 (1H, m), 8.52 (1H, d, J = 3 Hz), 8.87 (lH,d,J = lHz). MS (ESI+): m/z 346 (M+ + Na). Preparation 287 ethyl 7-methoxy-5-[(5-melhoxy-3-pyridinyl)carbonyl]-6-oxoheptanoale 1H NMR (CDCI3) 5 1.23 (3H, t, J = 8 Hz), 1.54-1.74 (2H, m), 1.84 (1H, m), 2.02 (1H, m), 2.32 (2H, d, J = 8 Hz), 3.26 (3H, s), 3.92 (3H, s), 3.99 (2H, d, J = 5 Hz), 4.10 (2H, q, J = 8 Hz), 4.70 (1H, t, J = 8 Hz), 7.71 (1H, m), 8.51 (1H, d, J = 3 Hz), 8.79(lH,brs). MS (ESI+): m/z 338 (M + H). Preparation 288 ethyl 8-melhoxy-7-oxo-6-(5-pyrimidinylcarbonyl)octanoate 1H NMR (CDCl3) 0 1.23 (3H, t, J = 8 Hz), 1.25-1.45 (2H, m), 1.55-1.70 (2H, m), 1.81 (1H, m), 2.03 (1H, m), 2.28 (2H, t, J = 8 Hz), 3.24 (3H, s), 3.92 (1H, d, J = 18 Hz), 4.01 (1H, d, J = 18 Hz), 4.10 (2H, q, J = 8 Hz), 9.26 (2H, s), 9.40 (1H, s). MS (ES1+): m/z 323 (M + H). Preparation 289 ethyl 5-[(5-chloro-3-pyridinyl)carbonyl]-7-methoxy-6-oxoheptanoate 1H NMR (CDCI3) 6 1.24 (3H, t, J = 8 Hz), 1.52-1.74 (2H, m), 1.83 (1H, m), 2.02 (1H, m), 2.34-2.40 (2H, m), 3.25 (3H, s), 3.92 (1H, d, J = 16 Hz), 4.01 (1H, d, J = 16 Hz), 4.11 (2H, q, J = 8 Hz), 4.68 (1H, t, J = 8 Hz), 8.23 (1H, br s), 8.78 (1H, br s), 9.05(lH,brs). MS (ESI+): m/z 342 (M + H). Preparation 290 ethyl 4-[(5-chloro-3-pyridinyl)carbony]]-6-methoxy-5-oxohexanoate !H NMR (CDCb) 6 1.25 (3H, t, J = 8 Hz), 2.09 (1H, m), 2.25 (1H, m), 2.38-2.49 (2H, m), 3.22 (3H, s), 3.91 (1H, d, J = 18 Hz), 4.00 (1H, d, J = 18 Hz), 4.14 (2H, q, J = 8 Hz), 4.85 (1H, m), 8.33 (1H, br s), 8.78 (1H, br s), 9.14 (1H, br s). MS (ES1+): m/z 328 (M+ H). Preparation 291 ethyl 6-[(5-chloro-3-pyridinyl)carbonyl]-8-methoxy-7-oxooctanoate 1H NMR (CDCI3) 6 1.23 (3H,t, J = 8 Hz), 1.27-1.43 (2H,m), 1.50-1.71 (2H, m), 1.82 (1H,m), 2.00 (1H, m), 2.27 (2H, d, J = 8 Hz), 3.25 (3H, s), 3.92 (1H, d, J = 16 Hz), 4.02 (1H, d, J = 16 Hz), 4.10 (2H, q,J = 8 Hz), 4.63 (1H, t, J = 8 Hz), 8.23 (1H, br s), 8.78 (1H, br s), 9.03 (1H, br s). MS (ES1+): m/z 356 (M + H). Preparation 292 2-[2-({3-[(5-methyl-3-pyridinyl)carbonyl]-4-oxopentyl}oxy)ethoxy]elhyl acetate trifluoroacctale 1H-NMR (CDCI3) 5 2.06 (3H, s), 2.28 (3H, s), 2.33 (2H, m), 2.65 (3H, s), 3.47-3.67 (8H, m), 4.17 (2H, m), 4.71 (1H, t, J = 7 Hz), 8.66 (1H, m), 8.88 (1H, m), 9.31 (lH,m). reparation 293 hyl 5-[(5-bromo-3-pyridinyl)carbonyl]-7-rnethoxy-6-oxoheptanoale 1H NMR (CDCI3) 5 1.23 (3H, t, J= 7 Hz), 1.56-1.73 (2H, m), 1.77-1.92 (1H, m), 1.96-2.10 (1H, m), 2.32 (2H, t, J= 7 Hz), 3.25 (3H, s), 3.92 (1H, d, J= 17 Hz), 4.02 (1H, d, J= 17 Hz), 4.12 (2H, q, J= 7 Hz), 4.67 (1H, t, J= 7 Hz), 8.39 (1H, m), 8.87 (1H, d, J= 2 Hz), 9.09 (1H, d, J= 2 Hz). MS(ESI+):m/z386 388. The following compound(s) was(were) obtained in a similar manner to that of Preparation 129 and 130. Preparation 294 tert-butyl 3-oxo-4-phenylbutanoate 1H NMR (CDCI3) 6 1.46 (9H, s), 3.37 (2H, s), 3.82 (2H, s), 7.21 (2H, d, J= 8 Hz), 7.25-7.37 (3H,m). Preparation 295 tert-butyl 3-oxo-3-phenylpropanoate 1H NMR (CDC13) 5 1.43 (9H, s), 3.81 (2H, s), 7.40-7.52 (2H, m), 7.56-7.63 (1H, m), 7.94(2H,d,J=8Hz). Preparation 296 tert-butyl 4-(cyclohexylmethoxy)-3-oxobutanoate 1H NMR (CDCI3) 6 0.89-1.07 (2H,m), 1.13-1.40 (3H,m), 1.47 (9H, s), 1.60-1.83 (6H, m), 3.28 (2H, d, J= 7 Hz), 3.45 (2H, s), 4.06 (2H, s). Preparation 297 tert-butyl 4-(cyclopropylmethoxy)-3-oxobutanoate 1H NMR (CDCI3) 5 0.20-0.28 (2H, m), 0.55-0.64 (2H, m), 1.03-1.17 (1H, m), 1.47 (9H, s), 3.36 (2H, d, J= 7 Hz), 3.45 (2H, s), 4.15 (2H, s). Preparation 298 lert-bulyl 4-(2-methoxyethoxy)-3-oxobutanoate 1H NMR (CDC13) 5 1.47 (9H, s), 3.38 (3H, s), 3.44 (2H, s), 3.57 (2H, m), 3.70 (2H, m),4.20(2H,s). Preparation 299 lert-butyl 4-isobutoxy-3-oxobutanoate !H NMR (300 MHz, CDCI3) 8 0.93 (6H, d, J = 7 Hz), 145 (9H, s), 1.91 (1H, qt, J = 7, 7 Hz), 3.26 (2H, d, J = 7 Hz), 3.45 (2H, s), 4.07 (2H, s). Preparation 300 tert-butyl 3-(3-methyl-2-thienyl)-3-oxopropanoate !H-NMR (CDCI3) 6 1.47 (9H, s),2.57 (3H, s), 3.79 (2H, s), 6.96 (1H, d, J = 5 Hz), 7.44(lH,d,J=5Hz). Preparation 301 tert-butyl 3-(5-methyl-3-isoxazolyl)-3-oxopropanoate 1H-NMR (CDCI3) 6 1.475-1.57 (9H, m), 2.49 (3H, m), 3.95 (2H, s), 6.40 (1H, s). The following cornpound(s) was(were) obtained in a similar manner to that of Preparation 132. Preparation 302 ethyl (2E)-5-(3-cyanobenzoyl)-6-oxo-2-heptenoate 5H-NMR (CDCI3) 5 1.28 (3H, t, J = 7 Hz), 2.20 (3H, s), 2.88 (2H, m), 4.16 (2H, q, J = 7 Hz), 4.54 (1H, t, J = 7 Hz), 5.88 (1H, d, J = 16 Hz), 6.82 (1H, dt, J = 7 and 16 Hz), 7.65 (1H, t, J = 8Hz), 7.89 (1H, d, J = 8 Hz), 8.20 (1H, d, J = 8 Hz), 8.27 (1H, s). MS (ES1+): m/z 300.14 (M + H) Preparation 303 1-tert-butyl 7-ethyl 2-[(3-methyl-2-thienyl)carbonyl1Heptanedioate 1H-NMR (CDCb) 6 1.25 (3H,t J = 7 Hz), 1.35-1.51 (UH,m), 1.65 (2H, m), 1.96 (2H,m),230(2H,t,J = 7Hz),258(3H,s),3.94(lH,l,J = 7Hz),4.12(2H,q,J = 7 Hz),6.97 (1H, d, J = 5 Hz), 7.44 (1H, d, J = 5 Hz). Reparation 304 -tert-butyl 7-elhyl 2-[(5-methyl-3-isoxazolyl)carbonyl1Heptanedioate 1H-NMR (CDC13) 5 11.24 (3H, t, J = 7 Hz), 1.39 (9H,s), 1.67 (2H, m), 1.98 (2H,m), 2.49 (3H, s), 4.10 (2H, q, J = 7 Hz), 4.26 (1H, t, J = 7 Hz), 6.37 (1H, s). The following compound(s) was(were) obtained in a similar manner to that of Preparation 152. Preparation 305 methyl 7-oxo-7-(2-thienyl)heptanoate 1H-NMR (CDCb) 6 1.41 (2H, m), 1.63-1.82 (4H, m), 2.33 (2H, t, J = 7 Hz), 2.91 (2H, t, J = 7 Hz), 3.67 (3H, s), 1.73 (1H, m), 7.62 (1H, m), 7.70 (1H, m). The following compound(s) was(were) obtained in a similar manner to that of Preparation 153. Preparation 306 5-methoxynicotinoyl chloride hydrochloride Preparation 307 5-pyrimidinecarbonyl chloride hydrochloride Preparation 308 5-chloronicotinoyl chloride hydrochloride Preparation 309 methyl 2-bromo-4-(chlorocarbonyl)benzoate The following compound(s) was(were) obtained in a similar manner to that of Praparation 159. Preparation 310 1-terl-butyl 7-ethyl 2-(phenylacelyl)heptanedioate 1H NMR (CDCb) 6 1.24 (3H, t, J= 7 Hz), 1.18-1.50 (2H, m), 1.46 (9H, s), 1 .50-1.75 (2H, m), 1.75-1.88 (2H, m), 2.24 (2H, 1, J= 7 Hz), 3.47 (1H, t, J= 7 Hz), 3.81 (2H, s), 4.10 (2H, q, J= 7 Hz), 7.20 (2H, d, J= 8 Hz), 7.25-7.37 (3H, m). Preparation 311 tert-butyl 2-[2-(2-methoxy-2-oxoethoxy)ethyl]-3-oxobutanoate 1H NMR (CDCI3) 6 1.46 (9H, s), 2.04-2.23 (2H, m), 2.29 (3H, s), 3.54 (2H, t, J= 7 Hz), 3.69 (1H, t, J= 7 Hz), 3.74 (3H, s), 4.04 (2H, s). Preparation 312 tert-butyl 2-benzoyl-4-(2-methoxy-2-oxoethoxy)butanoate 1H NMR (CDCI3) 5 1-34 (9H, s), 2.26-2.40 (2H, m), 3.55-3.67 (2H, m), 3.70 (3H, s), 4.04 (2H, s), 4.57 (1H, t, J= 7 Hz), 7.47 (2H, t, J= 8 Hz), 7.56 (1H, m), 8.01 (2H, d,J=8Hz). Preparation 313 1-tert-butyl 6-ethyl 2-[(acetyloxy)acetyl1Hexanedioate 1H NMR (CDCI3) 6 1.25 (3H, t, J= 7 Hz), 1.48 (9H, s), 1.60-1.73 (2H, m), 1.82-1.95 (2H, m), 2.17 (3H, s), 2.32 (2H, t, 3= 7 Hz), 3.43 (1H, t, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 4.72 (1H, d, J= 17 Hz), 4.83 (1H, d, J= 17 Hz). Preparation 314 1-tert-butyl 5-ethyl 2-[(cyclohexylmethoxy)acetyl]pentanedioate 1H NMR (CDCI3) 6 0.85-1.06 (2H, m), 1.13-1.34 (3H, m), 1.26 (3H, t, J= 7 Hz), 1.45 (9H, s), 1.60-1.85 (6H, m), 2.08-2.23 (2H, m), 2.36 (2H, t, J= 7 Hz), 3.27 (2H, d, J= 7 Hz), 3.67 (1H, t, J= 7 Hz), 4.10 (2H, s), 4.12 (2H, q, J= 7 Hz). Preparation 315 1-tert-butyl 6-ethyl 2-[(cyclohexylmethoxy)acelyl1Hexanedioate 1H NMR (CDCI3) 6 0.88-1.06 (2H, m), 1.12-1.34 (3H, m), 1.25 (3H, t, J= 7 Hz), 1.45 (9H, s), 1.54-1.94 (10H, m), 2.32 (2H, t, J= 7 Hz), 3.27 (2H, d, J= 7 Hz), 3.56 (1H, t, J= 7 Hz), 4.09 (2H, s), 4.11 (2H, q, J= 7 Hz). MS(ESl+):m/z385. Reparation 316 1 -terl-butyl 6-ethyl 2-[(cyclopropylmethoxy)acetyl1Hexanedioate 1H NMR (CDCI3) 5 0.22-0.33 (2H, m), 0.54-0.64 (2H, m), 1.04-1.18 (1H, m), 1.25 (3H, t, J= 7 Hz), 1.45 (9H, s), 1.60-1.73 (2H, m), 1.83-1.95 (2H, m), 2.33 (2H, t, J= 7 Hz), 3.33 (2H, d, J= 7 Hz), 3.53 (1H, t, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 4.18 (2H,m). MS(ESI+):m/z343. Preparation 317 1 -tert-butyl 5-elhyl 2-[(cyclopropylmethoxy)acetyl]pentanedioate 1H NMR (CDCI3) 5 0.20-0.35 (2H, m), 0.56-0.64 (2H, m), 1.04-1.16 (1H, m), 1.26 (3H, t, J= 7 Hz), 1.45 (9H, s), 2.12-2.24 (2H, m), 2.38 (2H, t, J= 7 Hz), 3.36 (2H, m), 3.65 (1H, t, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 4.19 (2H, s). Preparation 318 1-tert-butyl 5-ethyl 2-[(2-methoxyethoxy)acetyl]pentanedioate 1H NMR (CDCI3) 6 1.25 (3H, t, J= 7 Hz), 1.46 (9H, s), 2.10-2.23 (2H, m), 2.38 (2H, t, J= 7 Hz), 3.37 (3H, s), 3.60 (2H, m), 3.62 (1H, t, J= 7 Hz), 3.70 (2H, m), 4.12 (2H, q, J= 7 Hz), 4.23 (1H, d, J= 17 Hz), 4.30 (1H, d, J= 17 Hz). MS(ESl+):m/z333. Preparation 319 1-tert-butyl 5-ethyl 2-(isobutoxyacetyl)pentanedioate 1H NMR (300 MHz, CDCI3) 5 0.93 (6H, d, J = 7 Hz), 1.26 (3H, t, J = 7 Hz), 1.45 (9H, s), 1.91 (1H, qt, J = 7,7 Hz), 2.13 (2H, m), 2.37 (2H, t, J = 7 Hz), 3.25 (2H, d, J = 7 Hz), 3.67 (1H, t, J = 7 Hz), 4.12 (2H, s), 4.13 (2H, q, J = 7 Hz). The following compound(s) was(were) obtained in a similar manner to that of Preparation 164. Preparation 320 methyl 2-bromo-4-[(5-ethyl-lH-pyrrol-2-yl)carbonyl]benzoate 1H-NMR (CDC13) 5 1 32 (3H, i, J = 7 Hz), 2.72 (2H, q, J = 7 Hz), 3.97 (3H, s), 6,10 (1H,m),6.77(lH,m),7.81(lH,d,J = 8Hz),7.85(1H,d,J = 8Hz),8.110H,s), 9.32QH,s,br). The following compound(s) was(were) obtained in a similar manner to that of Preparation 165. Preparation 321 tert-butyl 2-(2-{2-[2-(acetyloxy)ethoxy]ethoxy}ethyl)-3-oxobutanoate 1H-NMR (CDC13) 6 1.46 (9H, s), 2.00-2.17 (5H, m), 2.25 (3H, s), 3.45-3.70 (10H, m), 4.22 (2H,m). The following compound(s) was(were) obtained in a similar manner to that of Preparation 178. Preparation 322 isobutoxyacetic acid 1H NMR (300 MHz, CDCfe) 6 0.94 (6H, ds J = 7 Hz), 1.93 (1H, qt, J = 7,7 Hz), 3.34 (2H,d,J = 7Hz),4.12(2H,s). Preparation 323 To a suspension of 60% NaH (2.66 g) in DMF (20 mL) was added methyl hydroxyacetate (5.00 g) under ice-water cooling, and the mixture was stirred at 0 "C for 0.5 hour. To this was added 2-(2-bromoethoxy)tetrahydro-2H-pyran (12.8 g) under ice-water cooling, and the mixture was stirred at ambient temperature for 2 hours. The mixture was partitioned between AcOEt and water. The organic layer was separated, washed with water and brine, dried over MgSC>4, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and AcOEt (10:1 - 3:1) to give methyl [2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]acetate pale yellow oil (4.45 g). methyl [2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]acetate 1H NMR (CDCI3) 5 1.48-1.95 (6H, m), 3.46-3.57 (2H, m), 3.64-3.75 (2H, m), 3.76 (3H, s), 3.82-3.97 (2H, m), 4.20 (2H, s), 4.66 (1H, m). Preparation 324 A mixture of methyl [2-(tetr1Hydro-2H-pyran-2-yloxy)ethoxy]acetate (1.07 g) and pyridinium p-toluenesulfonate (24.6 mg) in MeOH (10 mL) was heated under reflux for 2 hours. After evaporation of solvent, the residue was purified by silica gel column chromatography eluting with a mixture of hexane and AcOEt (10:1 -1:3) to give methyl (2-hydroxyethoxy)acetate as colorless oil (555 mg). methyl (2-hydroxyethoxy)acetate 1H NMR (CDC13) 5 3.69 (2H, m), 3.76 (2H, m), 3.78 (3H, s), 4.16 (2H, s). Preparation 325 To solution of methyl (2-hydroxyethoxy)acetate (540 mg), imidazole (411 mg) and triphenylphosphine (1.37 g) in ether (2 mL) and CH3CN (1 mL) was added iodine (1.43 g) under ice-water cooling and the mixture was stirred at 0 for 2 hours. After insolubles were filterred off, the filtrates were diluted with AcOEt, washed with aq NaoSO3 solution and brine, dried over MgSO4, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and AcOEt (20:1 - 5:1) to give methyl (2-iodoethoxy)acetate as colorless oil (898 mg). methyl (2-iodoethoxy)acetate ]H NMR (CDCl3) 6 3.30 (2H, t, J= 7 Hz), 3.77 (3H, s), 3.84 (2H, t, J= 7 Hz), 4.17 (2H,s). Preparation 326 To a suspension of 60% N1H (1.02 g) in THF (50 mL) was added tert-butyl 4-(acetyloxy)-3-oxobutanoate (5.00 g) under ice-water cooling and the mixture was stirred at 0 °C for 0.5 hour. To this added ethyl 3-iodopropanoate (5.54 g) and the mixture was stirred at 50 C for 8 hours. The mixture was partitioned between AcOEt and water. The organic layer was separated, washed with brine, dried over MgS04, and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and AcOEt (20:1 - 3:1) to give 1-tert-butyl 5-ethyl 2-[(acetyloxy)acetyl]pentanedioale as yellow oil (4.27 g). 1-tert-butyl 5-ethyl 2-[(acetyloxy)acetyl]pentanedioate 1H NMR (CDCl3) 5 1.26 (3H, t, J= 7 Hz), 1.46 (9H, s), 2.14-2.24 (2H, m), 2.17 (3H, s), 2.36 (2H, U J= 7 Hz), 3.60 (1H, t, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 4.73 (1H, d, J= 18 Hz), 4.83 (1H, d, J= 18 Hz). Preparation 327 To a solution of benzyl 4-thiomorpholinecarboxylate (4.8 g) in methanol (30 mL) and H2O (20 mL) was added oxone (16.2 g) under ice water cooling and the mixture was stirred at ambient temperature for 2 hours. The solution was evaporated in vacuo and partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc. The combined organic layer was washed with water and brine, dried over MgS04 and evaporated in vacuo. The residue was purified by silica gel column chromatography eluting with a mixture of hexane and EtOAc to give benzyl 4-thiomorpholinecarboxylate 1,1-dioxide as a colorless solid (3.8 g). benzyl 4-thiomorpholinecarboxylate l?l-dioxide 1H NMR (300 MHz, CDC13) 5 3.02 (4H, br s), 4.01 (4H, t, J = 5 Hz), 5.16 (2H, s), 7.33-7.40 (1H,m). Preparation 328 To a solution of thiomorpholine (2 g) in IN NaOH (11.6 mL) was added benzyl chloridocarbonate (1.66 mL) under ice water cooling and the mixture was stirred at ambient temperature for 2 hours. The solution was neutrolized with IN HC1 and extracted with EtOAc twice. The combined organic layer was washed with water and brine, dried over MgS04 and evaporated in vacuo. The residue was purified by silica gel column chromatography to give benzyl 4-thiomorpholinecarboxylate as a colorless solid (4.8 g). benzyl 4-thiomorpholinecarboxylate 1H NMR (300 MHz, CDC13) 6 2.59 (4H, br s), 3.77 (4H, t, J = 5 Hz), 5.14 (2H, s), 7.30-7.41 (1H,m). Preparation 329 To a solution of benzyl 4-thiomorpholinecarboxylate 1,1 -dioxide (3.8 g) in methanol (32 mL) and 1,4-dioxane (8 mL) was added Palladium, 10 wt. % on activated carbon (380 mg) at ambient temperature. The mixture was stirred at ambient temperature for 4 hours under H2 (3.4 atom). The mixture was filtered and evaporated in vacuo to give thiomorpholine 1,1-dioxide as a colorless solid (2.22 g). thiomorpholine 1,1-dioxide 1H NMR (300 MHz, CDC13) 5 3.03 (4H, t, J = 5 Hz), 3.33 (4H, t, J = 5 Hz). MS(m/z)136(M+H). Preparation 330 To a suspension of [(5-chloro-4-mercapto~6-methyl-3-pyridinyl)oxy]acetic acid (10 g) in dichloromelhane (100 mL) was added Et3N (14 mL) in ice-MeOH bath. To this was added trifluoromethanesulfonic anhydride (143 mL) dropwise below lO'C over 30 min. After 2 hours the mixture was partitioned between CHCl3 and water. The aqueous layer was extracted with CHCl3 twice. The combined organic layer was dried over MgSO4 and evaporated in vacuo to give brown oil. The residue was purified by silica gel column chromatography (silica gel, 100 mL) eluted with hexane-EtOAc = 15-1 and 10-1 to give 5-chloro-3-pyridinyl trifluoromethanesulfonate (15.8 g) as a pale brown oil. 5-chloro-3-pyridinyl trifluoromethanesulfonate 1H NMR (300 MHz, CDC13) 8 7.69 (1H, dd, J = 4,4 Hz), 8.52 (1H, d, J = 4 Hz), 8.65 (lH,d,J=4Hz). Preparation 331 To ethanol (66 mL) and DMF (66 mL) was added Et3N (29.4 mL), 1,3-propanediylbis(diphenylphosphine) (3.48 g) and palladium acetate (1.9 g) in ice-water bath. To this was added 5-chloro-3-pyridinyl trifluoromethanesulfonate (22.1 g) at the temperature. The mixture was stirred at 50˚C for 4 hours under CO (1 atom). The mixture was partitioned betwwen ElOAc and water. The aqueous layer was extracted with EtOAc. The combined organic layer was washed with water three times, dried over MgSO4 and evaporated in vacuo. The residue was purified by silica gel column chromatography (silica gel, 200 mL) eluted with hexane-EtOAc = 15-1 and 10-1 to give ethyl 5- chloronicolinale (10.5 g) as a pale brown oil. ethyl 5-chloronicotinate 1HNMR(300MHz5CDCl3)5l.42(3H,t,J = 7Hz),4.43(2H,q3J = 7Hz),8.28(lH, dd, J = 3,3 Hz), 8.74 (1H, d, J = 3 Hz), 9.09 (1H, d, J = 3 Hz). Preparation 332 To 5-chloronicotinate (10.5 g) was added IN NaOH (84.9 mL) at ambient temperature. The mixture was heated at 60°C for 1 hour. The reaction mixture was adjusted to pH 4-5 with HC1. The precipitate was filtered to give 5-chloronicotinic acid (6.9 g) a colorless solid. 1H NMR (300 MHz, DMSO-d6) 6 8.30 (1H, dd, J = 3 Hz), 8.88 (1H, d, J = 3 Hz), 9.01 (1H, d, J = 3 Hz), 13.8 (1H, br s). 5-chloronicotinic acid 1H NMR (300 MHz, DMSO-d6) 5 8.30 (1H, dd, J = 3,3 Hz), 8.88 (1H, d, J = 3 Hz), 9.01 (1H, d, J = 3 Hz), 13.8 (1H, br s). The following compound(s) was(were) obtained in a similar manner to that of Preparation 332. Preparation 333 5-methoxynicotinic acid 1H NMR (DMSO-d6) 8 3.87 (3H, s), 7.73 (1H, m), 8.48 (1H, d, J = 3 Hz), 8.65 (1H, d, J = 1 Hz). MS(ESl+):m/zl54(M + H). Preparation 334 5-pyrimidinecarboxylic acid 1H NMR (DMSO-d6) 6 9.20 (2H, s), 9.37 (1H, s). MS (ESI+): m/z 148 (M+ + Na). Preparation 335 To a solution of diisopropylamine (5.41 g) in THF (30 mL) was added 1.5 M n- butyllithium hexane solution (35 mL) under dryice acetone cooling and the mixture was stirred at -78 °C for 10 minutes. To this was added lert-butyl acetate (5.87 g) under dryice acetone cooling and the mixture was stirred at -78 ˚C for 10 minutes and added dropwise to a solution of 5-bromonicotinic acid (3.00 g) and N, N-carbonyldiimidazole (2.65 g) in THF (30 mL) under dryice acetone cooling. The mixture was stirred at -78 °C for 0.5 hour. The mixture was partitioned between ethyl acetate and aq NH4CI solution. The organic layer was separated, washed with aq N1HC03 solution and brine, dried over MgS04, and evaporated in vacuo. The residue was triturated with isopropyl ether to give tert-butyl 3-(5-bromo-3-pyridinyl)-3-oxopropanoate as a colorless powder (3.71 g). tert-butyl 3-(5-bromo-3-pyridinyl)-3-oxopropanoate Enol form:1H NMR (CDCl3) 6 1.54 (9H, s), 5.62 (1H, s), 8.19 (1H, m), 8.72 (1H, d, J= 2 Hz), 8.86 (1H, d, J= 2 Hz). Keto form:1H NMR (CDCl3) 8 1.44 (9H, s), 3.90 (2H, s), 8.37 (1H, m), 8.86 (1H, d, J= 2 Hz), 9.03 (1H, d, J= 2 Hz). MS (ESf): m/z 300 302. Preparation 336 To a suspension of N1H in DMF (50 mL) which was washed with hexane 3 times was added methyl 5-hydroxynicotinate (10.2 g) portionwise below lO'C in an ice-water bath under nitrogen atmosphere. After 30 min, methyl iodide (4.56 mL) was added dropwise therein. The precipitate appeared and the mixture was hard to be stirred. DMF (30 mL) was added. After 20 min, the mixture was stirred at ambient temperature for 3 h. The reaction mixture was quenched with MeOH and was concentrated in vacuo. To the residue was added CHCl3, sat. N1HCO3, and brine. The organic layer was separated and the aqueous layer was extracted with CHCl3. The combined organic layer was dried over MgSCU and was evaporated in vacuo. The residue was purified by flash silica gel chromatography (silica gel, 200 mL) eluted with hexane-AcOEt - 5-1 and 3-1 to give methyl 5-methoxynicotinate (3.47 g) as a pale brown solid . methyl 5-methoxynicotinate 1H NMR (CDCl3) 6 3.91 (3H, s), 3.96 (3H, s), 7.76 (1H, m), 8.47 (1H, d, J = 3 Hz), 8.83 (1H, d, J = 1 Hz). MS(ESl+):m/zl68(M + H). Preparation 337 To a solution of methyl 2-bromo-4-[(5-ethyl-lH-pyrrol»2-yl)carbonyl]benzoate (330 mg) in N,N-dimethylformamide (5 mL) was added 60% sodium hydride in oil (58.4 mg) in an ice-bath over 5 miutes. After stirring for 1 hour, (aminooxy)(diphenyl)phosphine oxide (340 mg) was added portionwise over 40 minutes. The resulting mixture was stirred for 1 hour in the bath. The reaction was quenched by adding water (10 mL). The mixture was partitioned between ethyl acetate and water. The organic layer was washed with water (two times) and brine, dried over magnesium sulfate, and evaporated. The residue was dissolved in ethyl acetatec-hexane (1-5), and to the solution was added silicagel. The mixture was filtered, and the filtrate was evaporated to give methyl 4-[(l-amino-5-ethyl-lH-pyrrol-2-yl)carbonyl]-2-bromobenzoate as an orange solid (310 mg). methyl 4-[(l-amino-5-ethyl-lH-pyrrol-2-yl)carbonyl]-2-bromobenzoate 1H-NMR (CDCl3) 6 1.29 (3H, t, J = 7 Hz), 2,76 (2H, q, J = 7 Hz), 3.97 (3H, s), 5.73 (2H, s, br), 5.93 (1H, d, J = 5 Hz), 6.62 (1H, d, J = 5 Hz), 7.73 (1H, d, J = 8 Hz), 7.84 (lH, d, J = 8 Hz), 8.02 (1H, s). Preparation 338 To a solution of dimethyl 2-bromoterephthalate (1.04 g) in methanol (10 mL) was added 1 N sodium hydroxide (5.71 mL) at room temperature. After stirring for 1.5 hour, the reaction was quenched by adding 1 N hydrochloric acid (7 mL). White crystals were formed. Water (10 mL) was added to aid crystalyzation. The crystals were collected by filtration, washed with water, and dried in the air. 3-Bromo-4-(methoxycarbonyl)benzoic acid was obtained as white crystals (532 mg). 3-bromo-4-(methoxycarbonyI)benzoicacid 'H-NMR (DMSO-d6) 5 3.89 (3H, s), 7.87 (1H, d, J ˚ 8 Hz), 8.01 (1H, d, J = 8 Hz), 8.17 (lH,s). Preparation 339 A mixture of 2-[2-(2-ch]oroethoxy)ethoxy]ethyl acetate (6.23 g) and sodium iodide (22.2 g) in acetone (60 mL) was refluxed for 4 hours. The mixture was further refluxed for 4 hours after adding sodium iodide (J 1.0 g). The solvent was evaporated off, and the residue was partitioend between EtOAc (50 mL) and water (50 mL). The aqueous layer was washed with 10% sodium thiosulfate and brine, dried over MgSO4, and evaporated to give 2-[2-(2-iodoethoxy)ethoxy]ethyl acetate as a pale yellow oil (9.74 g)- 2-[2-(2-iodoethoxy)ethoxy]ethyl acetate 'H-NMR (CDC13) 6 2.09 (3H, s), 3.27 (2H, t, J = 7 Hz), 3.65-3.78 (8H, m), 4.24 (2H, m). Preparation 340 A solution of 1-tert-butyl 7-ethyl 2-[(5-metbyl-3~ isoxazolyl)carbonyl1Heptanedioate (126 mg) in trifluoroacetic acid (1 mL) was stirred for 1.5 hour at room temperature. The volatile was evaporated off, and azeotroped with toluene to give 7-ethoxy-2-[(5-methyl-3-isoxazolyl)carbonyl]-7-oxoheptanoic acid as a pale orange oil (106 mg). 7-ethoxy-2-[(5-methyl-3-isoxazolyl)carbonyl]-7-oxoheptanoic acid 'H-NMR (CDCl3) 6 1.24 (3H, t, J = 7 Hz), 1.41 (2H, m), 1.65 (2H, m), 2.02 (2H, m), 2.30 (2H, m), 2.50 (3H, s), 2.55 (1H, s, br), 4.10 (2H, q, J = 7 Hz), 4.47 (1H, t, J = 7Hz),6.40(lH,s). MS (ESI+): m/z 296.22 (M-H) and 593.52 (2M-H) Preparation 341 To a suspension of dimethyl sulfone (5.43 g) in tetr1Hydrofuran (10 mL) was addded 1.59 M n-butyl lithium (36.3 mL) in a dryice-acetone bath under a nitrogen atmosphere. After stirring for 0.5 hour, a solution of methyl methoxyacetate (2.00 g) in tetr1Hydrofuran (5 mL) was added. The resulting mixture was stirred for 2 hours in the bath and allowed to warm to room temperature over 2 hours. The mixture was partitioned between EtOAc and 4 N hydrochloric acid. The reaction was quenched by adding 4 N hydrochloric acid in EtOAc (15 mL). The mixture was partitioned between EtOAc (100 mL) and brine (100 mL). The aqueous layer was washed with EtOAc (100 mL, five times). The organic layer was combined, and the combined extracts were dried over MgS04, and evaporated. Flash silicagel column chromatography (EtOAc-hexane = 50-200 to 300-100) afforded 2-(methylsulfonyl)-l~methoxyethanone as a colorless oil (2.24 g). l-methoxy-3-(methylsulfonyl)acetone 1H-NMR (CDC13) 6 2.99 (3H, s), 3.08 (2H, s), 3.47 (3H, s), 4.19 (2H, s). The following compound(s) was(were) obtained in a similar manner to that of Example 1. Example 392 ethyl 4-[3-bromo-4-(methoxycarbonyl)phenyl]-7-ethyl-2-methylpyrrolo[l,2-b]pyridazine-3-carboxylate 1H-NMR (CDCl3) 6 0.98 (3H, t, J = 7 Hz), 1.38 (3H, t, J = 7 Hz), 2.61 (3H, s), 3.04 (2H, q, J = 7 Hz), 3.98 (3H, s), 4.05 (2H, q, J = 7 Hz), 6.29 (1H, d, J = 5 Hz), 6.67 (1H, d, J = 7 Hz), 7.44 (1H, d, J = 8 Hz), 7.76 (1H, s), 7.89 (1H, d, J = 8 Hz). Example 393 3-[7-ethyI-2-(methoxymethyl)-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazin-4- yl]benzonitrile 1H-NMR (CDCl3) 6 1.38 (3H, t, J = 7 Hz), 2.98 (2H, q, J = 7 Hz), 3.18 (3H, s), 3.45 (3H, s), 4.59 (2H, s), 6.25 (1H, d, J = 5 Hz), 6.71 (1H, d, J = 5 Hz), 7.65 (1H, t, J = 8 Hz), 7.78 (1H, d, J = 8 Hz), 7.94 (1H, d, J = 8 Hz), 7.99 (1H, s). MS(ESI+):m/z370(M + H) The following compound(s) was(were) obtained in a similar manner to that of Example 16. Example 394 5-{4-[3-(aminocarbonyl)phenyl]-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl}pentanoic acid 1H-NMRCCDCL2) 6 1.02 (4H,m), 1.28 (3H,t, J = 7 Hz), 1.70 (2H,m), 2.37 (2H,m), 2.92 (2H, q, J = 7 Hz), 5.87 (1H, d, J = 5 Hz), 6.66 (1H, d, J = 5 Hz), 7.46-7.67 (1H,m), 7.96-8.08 (3H,m). The following compound(s) was(were) obtained in a similar manner to that of Example 21. Example 395 ethyl 4-[4-(2-chloro-4-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]butanoate 1H NMR (CDC13) 8 1.21 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.65-1.78 (2H, m), 2.22 (2H, t, J= 7 Hz), 2.40-2.52 (2H, m), 2.58 (3H, s), 3.03 (2H, q, J= 7 Hz), 4.05 (2H, q, J= 7 Hz), 5.86 (1H, d, J= 4 Hz), 6.53 (1H, d, J= 4 Hz), 7.25 (1H, d, J= 5 Hz), 7.36 (1H, s), 8.53 (1H, d, J= 5 Hz). MS (ESI+): m/z 386 . Example 396 ethyl 3-[4-(2-chloro-4-pyridinyl)-7-ethyl-2-methylpyrrolo[l ,2-b]pyridazin-3- yl]propanoate 1H NMR (CDCl3) 5 1.24 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 2.30-2.39 (2H, m), 2.57 (3H, s), 2.74-2.83 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 5.88 (1H, d, J= 4 Hz), 6.55 (1H, d, J= 4 Hz), 7.24 (1H, d, J= 5 Hz), 7.35 (1H, s), 8.53 (lH,d,J=1Hz). MS (ESI+): m/z 372. Example 397 ethyl 5-[2-benzyl-4-(2-chloro-4-pyridinyl)-7-ethylpyrrolo[l,2-b]pyridazin-3- yl]pentanoate 1H NMR (CDCl3) 6 1.23 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 1.30-1.50 (4H, m), 2.10 (2H, t, J= 7 Hz), 2.23-2.35 (2H, m), 3.04 (2H, q, J= 7 Hz), 4.09 (2H, q, J= 7 Hz), 4.21 (2H, s), 5.88 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.14-7.32 (7H, m), 8.50(lH,d,J=1Hz). Example 398 methyl {2-[7-ethyl-2-methyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3- yl]ethoxy}acetate 1H NMR (CDCl3) 5 137 (3H, t, J= 7 Hz), 2.42 (3H, s), 2.61 (3H, s), 2.78-2.88 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.46-3.57 (2H, m), 3.71 (3H, s), 3.95 (2H, s), 5.87 (1H, d, J= 4 Hz), 6.52 (1H,d,J= 4 Hz), 7.54 (1H, s), 8.43 (1H, d, J= 2 Hz), 8.53 (JH, d, J=2Hz). MS (ES1+): m/z 368. Example 399 ithyl [4-(5-bromo-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]acetate1H NMR (CDCl3) 6 1.26 (3H, t, J= 7 Hz), 1.38 (3H, t, J= 7 Hz), 2.51 (3H, s), 3.03 (2H, q, J= 7 Hz), 3.43 (2H, s), 4.12 (2H, q, J= 7 Hz), 5.99 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.94 (1H, m), 8.58 (1H, d, J= 2 Hz), 8.78 (1H, d, J= 2 Hz). MS(ESl+):m/z402 404. Example 400 ethyl 3-[2-[(acetyloxy)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin- 3-yl]propanoate 1H NMR (CDCl3) 5 1.24 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 2.16 (3H, s), 2.32-2.42 (2H, m), 2.44 (3H, s), 2.77-2.90 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 5.31 (2H, s), 5.96 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.53 (1H, s), 8.42 (1H, d, J=2 Hz), 8.55 (1H, d, J= 2 Hz). MS (ESI+): m/z 410. Example 401 ethyl 4-[2-[(acetyloxy)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin- 3-yl]butanoate 1H NMR (CDC13) 5 1.25 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.64-1.78 (2H, m), 2.10-2.23 (2H, m), 2.17 (3H, s), 2.43 (3H, s), 2.43-2.58 (2H, m), 3.02 (2H, q, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 5.33 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 7.53 (1H, s), 8.43 (1H, s), 8.55 (1H, s). MS (ES1+): m/z 424. Example 402 ethyl 5-[2-[(acetyloxy)methyl]-4-(3-cyanophenyl)-7-ethylpyrrolo[l,2-b]pyridazin-3- yljpentanoate 1HNMR (CDC13) 6 1.24 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.40-1.60 (4H, m), 2.16 (2H, t, J= 7 Hz), 2.17 (3H, s), 2.40-2.52 (2H,m), 3.03 (2H, q, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 5.29 (2H, s), 5.88 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.60- 7.68 (3H,m), 7.75-7.83 (lH,m). MS(ESl+):m/z448. Example 403 ethyl 4-[2-[(acetyloxy)methyl]-4-(5-bromo-3-pyridinyl)-7-ethylpyrrolo[ 1,2-b]pyridazin-3- yl]butanoate 1H NMR (CDCl3) 6 1.22 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.65-1.82 (2H, m), 2.17 (3H, s), 2.21 (2H, t, J= 7 Hz), 2.45-2.63 (2H, m), 3.02 (2H, q, J= 7 Hz), 4.05 (2H, q, J= 7 Hz), 5.33 (2H, s), 5.95 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.90 (1H, m), 8.57 (1H, d, J= 2 Hz), 8.80 (1H, d, J= 2 Hz). MS (ESI+): m/z 488 490. Example 404 ethyl 3-[2-[(acetyloxy)methyl]-4-(5-bromo-3-pyridinyl)-7-ethylpyrrolo[l,2-b]pyridazin-3- yl]propanoate 1H NMR (CDC13) 8 1.23 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 2.16 (3H, s), 2.36 (2H, t, J= 7 Hz), 2.77-2.95 (2H, m), 3.02 (2H, q, J= 7 Hz), 4.06 (2H, q, J= 7 Hz), 5.31 (2H, s), 5.96 (1H, d, J= 4 Hz), 6.64 (1H, d, J= 4 Hz), 7.88 (1H, s), 8.56 (1H, m),8.80(lH,m). MS(ESl+):m/z474 476. Example 405 ethyl 3-[2-[(cyclohexylmethoxy)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2- b]pyridazin-3-yl]propanoate 1H NMR (CDCl3) 8 0.88-1.06 (2H, m), 1.19 (3H, t, J= 7 Hz), 1.15-1.36 (3H, m), 1.37 (3H, t, J= 7 Hz), 1.58-1.85 (6H, m), 2.42 (2H, m), 2.43 (3H, s), 2.83-2.97 (2H, m), 3.05 (2H, q, J= 7 Hz), 3.38 (2H, d, J= 7 Hz), 4.06 (2H, q, J= 7 Hz), 4.66 (2H, s), 5.91 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.52 (1H, s), 8.42 (1H, d, J= 2 Hz), 8.54(lH,d,J=2Hz). Example 406 hyl 3-{4-(5-bromo-3-pyridinyl)-2-[(cyclohexylmelhoxy)melhyJ]-7-ethy]pyrrolo[ 1,2-|pyiidazin-3-yl}propanoate1H NMR (CDCb) 6 0.85-1.06 (2H, m), 1.20 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), J .1 6-1.46 (3H, m), 1.55-1.84 (6H, m), 2.43 (2H, t, J= 7 Hz), 2.82-3.00 (2H, m), 3.06 (2H, q, J= 7 Hz), 3.37 (2H,d, J= 7 Hz), 4.06 (2H, q, J= 7 Hz), 4.66 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.87 (1H, m), 8.55 (1H, d, J= 2 Hz), 8.78(lH,d,J=2Hz). MS (ES1+): m/z 528 530. Example 407 ;thyl 4-{4-(5-bromo-3-pyridinyl)-2-[(cyciohexylmethoxy)methy]]-7-ethylpyrrolo[l,2- 3]pyridazin-3-yl}butanoate 1H NMR (CDC13) 6 0.87-1.06 (2H, m), 1.21 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.16-1.46 (3H, m), 1.50-1.85 (8H, m), 2.23 (2H, t, J= 7 Hz), 2.55-2.75 (2H, m), 3.04 (2H, q, J= 7 Hz), 3.38 (2H, d, J= 7 Hz), 4.08 (2H, q, J= 7 Hz), 4.67 (2H, s), 5.92 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 7.89 (1H,m), 8.56 (1H, d, J= 2 Hz), 8.79(lH,d,J=2Hz). MS(ESI+):m/z542 544. Example 408 ethyl 4-[2-[(cyclopropylmethoxy)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2- b]pyridazin-3-yl]butanoate 1H NMR (CDC13) 6 0.22-0.32 (2H, m), 0.53-0.65 (2H, m), 1.10-1.20 (1H, m), 1.19 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 1.65-1.80 (2H, m), 2.14-2.30 (2H, m), 2.43 (3H, s), 2.57-2.74 (2H, m), 3.05 (2H, q, J= 7 Hz), 3.43 (2H, d, J= 7 Hz), 4.03 (2H, q, J= 7 Hz), 4.74 (2H, s), 5.90 (1H, d, J= 4 Hz), 6.57 (1H, d, J= 4 Hz), 7.53 (1H, s), 8.43 (lH,s), 8.54 (lH,s). MS (ES1+): m/z 436. Example 409 clhy] 3-[2-[(cyclopropylmethoxy)methyl]-7-ethyl-4-(5-methyl-3-pyriclinyl)pyrro]ol],2-b]pyridazin-3-yl]propanoate 1H NMR (CDCb) 5 0.22-0.32 (2H, m), 0.54-0.63 (2H, m), J .10-1.20 (1H, m), 1.21 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 2.40-2.50 (2H, m), 2.43 (3H, s), 2.86-2.98 (2H, m), 3.05 (2H, q, J= 7 Hz), 3.42 (2H, d, J= 7 Hz), 4.06 (2H, q, J= 7 Hz), 4.71 (2H, s), 5.92 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 7.52 (1H, s), 8.42 (1H, s), 8.54 (1H, s). MS (ESI+): m/z 422. Example 410 ethyl 3-{4-(5-bromo-3-pyridinyl)-7-ethyl-2-[(2-methoxyethoxy)methyl]pyrrolo[l,2- b]pyridazin-3-yl}propanoate 1H NMR (CDC13) 6 1.20 (3H, t, J= 7 Hz), 1.37 (3H, t, J= 7 Hz), 2.44 (2H, t, J= 7 Hz), 2.82-2.98 (2H, m), 3.05 (2H, q, J= 7 Hz), 3.38 (3H, s), 3.58 (2H, m), 3.76 (2H, m), 4.05 (2H, q, J= 7 Hz), 4.76 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.87 (1H, m), 8.54 (1H, s), 8.79 (1H, s). MS (ESI+): m/z 490 492. Example 411 4-(5-bromo-3-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazine 1H NMR (CDC13) 5 1.39 (3H, t, J= 7 Hz), 2.54 (3H, s), 3.04 (2H, q, J= 7 Hz), 6.39 (1H, s), 6.51 (1H, d, J= 4 Hz), 6.67 (1H, d, J= 4 Hz), 8.17 (1H, m), 8.76 (1H, d, J=2Hz),8.86(lH,d,J=2Hz). MS(ESI+):m/z316 318. Example 412 ethyl 4-[2-[(acetyloxy)methyl]-4-(5-chloro-3-pyridinyl)-7-ethylpyrrolo[l,2-b]pyridazin-3- yl]butanoate 1H NMR (300 MHz, CDCl3) 5 1.20 (3H, t, J = 7 Hz), 1.37 (3H, t, J = 7 Hz), 1.70 (2H, tt, J = 7,7 Hz), 2.17 (3H, s), 2.20 (2H, t, J = 7 Hz), 2.45-2.54 (2H, m), 3.02 (2H, q, J = 7 Hz), 4.04 (2H, q, J = 7 Hz), 5.33 (2H, s), 5.94 (1H, d, J = 4 Hz), 6.63 (1H, d, J = 4 Hz), 7.74 (1H, dd, J = 2,2 Hz), 8.53 (1H, d, J = 2 Hz), 8.70 (1H, d, J = 2 Hz). Example 413 ethyl 5-{4~(5-ch]oro-3-pyridiny])-2-[(cyclopropylmethoxy)methyl]-7-ethy]pyrrolo[l,2- b]pyridazin-3-yl}pentanoate 1H NMR (300 MHz, CDC13) 6 0.23-0.26 (2H, m), 0.54-0.59 (2H, m), 1.07-1.16 (1H, m), 1.23 (3H, t, J = 7 Hz), 1.37 (3H, t, J = 7 Hz), 1.41-1.56 (4H, m), 2.17 (2H, t, J = 7 Hz), 2.53-2.64 (2H, m), 3.03 (2H, q, J =7 Hz), 3.41 (2H, d, J = 7 Hz), 4.09 (2H, q, J = 7 Hz), 4.70 (2H, s), 5.90 (1H,d, .1 = 5 Hz), 6.58 (1H, d, J = 5 Hz), 7.72 (lH,s),8.51 (1H,S),8.68(1H,S). Example 414 ethyl 4-{4-(5-chloro-3-pyridinyl)-2-[(cyclopropylmethoxy)methyl]-7-ethylpyrrolo[l,2- b]pyridazin-3-yl}butanoate 1H NMR (300 MHz, CDCl3) 6 0.24 (2H, dt, J = 7,7 Hz), 0.56 (2H, dt, J = 7, 7 Hz), l.07-1.15 (lH,m), 1.20 (3H,t, J = 7 Hz), 1.37 (3H,t, J = 7 Hz), 1.72 (2H, tt, J = 7, 7 Hz), 2.21 (2H, t, J = 7 Hz), 2.55-2.66 (2H, m), 3.02 (2H, q, J = 7 Hz), 3.43 (2H, d, J = 7 Hz), 4.04 (2H, q, J = 7 Hz), 4.73 (2H, s), 5.91 (1H, d, J = 5 Hz), 6.59 (1H, d, J = 5 Hz), 7.74 (1H, dd, J = 2, 2 Hz), 8.52 (1H, d, J = 2 Hz), 8.68 (1H, d, J = 2 Hz). Example 415 ethyl 5-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(isobutoxymethyl)pynolo[l,2-b]pyridazin-3- yljpentanoate 1H NMR (300 MHz, CDCb) 6 0.92 (6 H, d, J = 7 Hz), 1.26 (3H, t, J = 7 Hz), 1.34 (3H, t, J = 7 Hz), 1.38-1.56 (4H, m), 1.92 (1H, qt, J = 7, 7 Hz), 2.15 (2H, 1, J = 7 Hz), 2.51-2.63 (2H, m), 3.03 (2H, q, J = 7 Hz), 3.33 (2H, d, J = 7 Hz), 4.09 (2H, q, J = 7 Hz), 4.65 (2H, s), 5.90 (1H, d, J = 7 Hz), 6.59 (1H, d, J = 7 Hz), 7.88 (1H, dd, J = 2,2 Hz), 8.55 (1H, d, J = 2 Hz), 8.77 (1H, d, J = 2 Hz). Example 416 ethyl 3-[4-(5-chloro-3-pyridinyI)-7-ethyl-2-(isobutoxymethyl)pyrrolo[l,2-b]pyridazin-3- yl]propanoate 1H NMR (300 MHz, CDCl3) 5 0.92 (6H, d, J = 7 Hz), 1.19 (3H, t, J = 7 Hz), 1.37 (3H, I, J = 7 Hz), 1.91 (1H, ql, J = 7,7 Hz), 2.41 (2H, t, J = 8 Hz), 2.84-2.94 (2H, m), 3.03 (2H, q, J = 7 Hz), 3.35 (2H, d, J = 7 H), 4.05 (2H, q, J = 7 Hz), 4.68 (2H, s), 5.92 (1H, d, J = 4 Hz), 6.61 (1H, d, J =4 Hz), 7.72 (1H, dd, J = 2,2 Hz), 8.51 (1H, d, J = 2 Hz), 8.69 (1H, d, J = 2 Hz). Example 417 hyl 3-[2-[(acelyloxy)methyl]-4-(3-chlorophenyl)-7-ethylpyrrolo[l,2-b]pyridazin-3-l]propanoate 1H NMR (300 MHz, CDC13) 6 1.19 (3H, t, J = 7 Hz), 1.36 (3H, t, J = 7 Hz), 2.15 (3H, s), 2.33 (2H, t, J = 8 Hz), 2.82 (2H, t, J = 8 Hz), 3.02 (2H, q, J = 7 Hz), 4.06 (2H, q, J = 7 Hz), 5.31 (2H, s), 5.97 (1H, d, J = 4 Hz), 6.61 (1H, d, J = 4 Hz), 7.23-7.26 (1H, m), 7.37 (1H, s), 7.44-7.46 (2H, m). Example 418 :thyl 4-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(isobutoxymethyl)pyrrolo[l,2-b]pyridazin-3- /ljbutanoate 1H NMR (300 MHz, CDC13) 6 0.92 (6H, d, J = 7 Hz), 1.20 (3H, t, J = 7 Hz), 1.37 (3H, t, J = 7 Hz), 1.71 (2H, tt, J = 8, 8 Hz), 1.91 (1H, qt, J = 7, 7 Hz), 2.20 (2H, t, J = 8 Hz), 2.56-2.66 (2H, m), 3.03 (2H, q, J = 7 Hz), 3.34 (2H, d, J = 7 Hz), 4.05 (2H, q, J = 7 Hz), 4.69 (2H, s), 5.91 (1H, d, J = 5 Hz), 6.60 (1H, d, J = 5 Hz), 7.89 (1H, s), 8.56 (1H, d, J = 2 Hz), 8.78 (1H, d, J = 2 Hz). Example 419 2,4-bis(5-bromo-3-pyridinyl)-7-ethylpyrrolo[l,2-b]pyridazine 1H NMR (CDCl3) 6 1.45 (3H, t, J= 7 Hz), 3.14 (2H, q, J= 7 Hz), 6.66 (1H, d, J= 4 Hz), 6.86 (1H, d, J= 4 Hz), 6.91 (1H, s), 8.23 (1H, m), 8.48 (1H, m), 8.77 (1H, m), 8.83 (1H, m), 8.94 (1H, d, J= 2 Hz), 9.18 (1H, d, J= 2 Hz). Example 420 ethyl 4-[2-[(acetyloxy)methyl]-4-(3-chlorophenyl)-7-elhylpyrrolo[l,2-b]pyridazin-3- yl]butanoate 1H NMR (CDCl3) 6 1.19 (3H, t, J = 8 Hz), 1.34 (3H, t, J = 8 Hz), 1.63-1.76 (2H, m), 2.10-2.22 (1H, m), 2.45-2.55 (2H, m), 3.01 (2H, q, J = 8 Hz), 4.04 (2H, q, J = 8 Hz), 5.32 (2H, s), 5.95 (1H, d, J = 5 Hz), 6.59 (1H, d, J = 5 Hz), 7.21-7.29 (1H, overlappled with CDC1,), 7.36 (1H, br s), 7.38-7.46 (2H, m). MS (ESI+): m/z 443 (M + H). Example 421 elhyl 5-[7-ethyl-2-(methoxymethy])-4-(5-methoxy-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]propanoate 1H NMR (CDC13) 6 1.23 (3H, t, J = 8 Hz), 1.33-1.60 (7H, m), 1.55-1.70 (2H, m), 2.17 (2H, t, J = 8 Hz), 2.46-2.64 (2H, m), 3.04 (2H, d, J = 8 Hz), 3.46 (3H, s), 3.90 (3H, s), 4.09 (2H, q, J = 8 Hz), 4.62 (2H, s), 5.93 (1H, d, J = 5 Hz), 6.59 (1H, d, J = 5 Hz), 7.23 (1H, m), 8.22 (1H, d, J = 1 Hz), 8.40 (1H, d, J = 3 Hz). MS(ESI+):m/z426(M + H). Example 422 ethyl 5-[7-ethyl-4-(5-methoxy-3-pyridinyl)-2-methylpyrrolo[l,2-b]pyridazin-3- yl]pentanoate 1H NMR (CDCl3) 5 1.23 (3H, t, J = 8 Hz), 1.33-1.62 (7H, m), 2.18 (2H, t, J = 8 Hz), 2.38-2.49 (2H, m), 2.56 (3H, s), 3.01 (2H, q, J = 8 Hz), 3.90 (3H, s), 4.08 (2H, q, J = 8 Hz), 5.89 (1H, d, J = 5 Hz), 6.51 (1H, d, J = 5 Hz), 7.21 (1H, m), 8.21 (1H, d, J = 1 Hz), 8.40 (1H, d, J = 3 Hz). MS(ESI+):m/z396(M + H). Example 423 ethyl 3-[7-ethyl-2-(methoxymethyl)-4-(5-methoxy-3-pyridinyl)pyrrolo[l,2-b]pyndazin-3- yl]propanoate 1H NMR (CDCb) 5 1.20 (3H, t, J = 8 Hz), 1.38 (3H, t, J = 8 Hz), 2.40 (2H, t, J = 8 Hz), 2.81-2.96 (2H, m), 3.04 (2H, d, J = 8 Hz), 3.47 (3H, s), 3.90 (3H, s), 4.05 (2H, q, J = 8 Hz), 4.65 (2H, s), 5.96 (1H, d, J = 5 Hz), 6.60 (1H, d, J = 5 Hz), 7.21 (1H, m), 8.23 (1H, br s), 8.40 (1H, d, J = 3 Hz). MS (ES1+): m/z 398 (M + H). Example 424 ethyl 4-[7-ethyl-2-(methoxymethyl)-4-(5-methoxy-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3- yl]butanoafe 1H NMR (CDCl3) 6 1 -20 (1H, 1, J = 8 Hz), J .38 (1H, t, J = 8 Hz), 1.64-1.79 (2H, m), 2.14-2.24 (2H, m), 2.53-2.66 (2H, m), 3.04 (2H, d, J = 8 Hz), 3.47 (1H, s), 3.90 (1H, s), 4.04 (2H, q, J = 8 Hz), 4.67 (2H, br s), 5.94 (1H, d, J = 5 Hz), 6.59 (1H, d, J = 5 Hz), 7.23 (1H, m), 8.22 (1H, d, J = 1 Hz), 8.40 (1H, d, J = 3 Hz). MS(ESl+):m/z412(M+H). ;ample 425 Nyl 5-[7-ethyl-2-(methoxymethyl)-4-(5-pyrimidinyl)pyrrolo[l,2-b]pyridazin-3- Ipentanoate 1H NMR (CDCl3) 6 1.23 (1H, t, J = 8 Hz), 1.30-1.62 (7H, m), 2.19 (2H, t, J = 8 Hz), 2.46-2.60 (2H, m), 3.04 (2H, d, J = 8 Hz), 3.47 (1H, s), 3.90 (1H, s), 4.09 (2H, q, J = 8 Hz), 4.63 (2H, s), 5.90 (1H, d, J = 5 Hz), 6.61 (1H, d, J = 5 Hz), 8.80 (2H, s), 9.34 (lH,s). MS (ESI+): m/z 397 (M + H). ixample 426 thyl4-[4-(5-chloio-3-pyridinyl)-7-elhyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3- l]butanoate 1H NMR (CDCl3) 6 1.21 (1H, t, J = 8 Hz), 1.37 (1H, t, J = 8 Hz), 1.62-1.76 (2H, m), 2.21 (2H, t, J = 8 Hz), 2.49-2.67 (2H, m), 3.04 (2H, d, J = 8 Hz), 3.46 (1H, s), 4.06 (2H, q, J = 8 Hz), 4.67 (2H, br s), 5.92 (1H, d, J = 5 Hz), 6.61 (1H, d, J = 5 Hz), 7.74 (1H, m), 8.53 (1H, d, J = 1 Hz), 8.69 (1H, d, J = 2 Hz). MS(ESl+):m/z414(M-H). Example 427 ethyl 3-[4-(5-chloro-3-pyridinyl)-7-ethyl-2-(melhoxymethyl)pyrrolo[l,2-b]pyridazin-3- yl]propanoale 1H NMR (CDCl3) 6 1 -20 (1H, t, J = 8 Hz), 1.38 (1H, t, J = 8 Hz), 2.40 (2H, t, J = 8 Hz), 2.82-2.94 (2H, m), 3.04 (2H, d, J = 8 Hz), 3.47 (1H, s), 4.06 (2H, q, J = 8 Hz), 4.65 (2H, s), 5.93 (1H, d, J = 5 Hz), 6.67 (1H, d, J = 5 Hz), 7.73 (1H, br s), 8.51 (lH.br s), 8.70 (lH.br s). MS(ESl+):m/z402(M+H). Example 428 ethyl 5-[4-(5-chloro-3-pyridinyl)-7-ethyl-2-(methoxymelhyl)pyrrolo[l,2-b]pyricl'izin-3-]pentanoate 1H NMR (CDCL3) 6 1.23 (1H, t, J = 8 Hz), 1.34-1.60 (7H, m), 2.19 (2H, t, J = 8 Hz), 2.47-2.64 (2H, m), 3.04 (2H, d, J = 8 Hz), 3.46 (1H, s), 4.10 (2H, q, J = 8 Hz), 4.62 (2H, s), 5.90 (1H, d, J = 5 Hz), 6.60 (1H, d, J = 5 Hz), 7.73 (1H, m), 8.51 (lH,brs),8.68(lH,brs). MS (ESI+): m/z 426 (M + H). Example 429 nethyl 2-[(acetyloxy)methyl]-4-(5-bromo-3-pyridinyl)-7-ethylpyrrolo[l,2-b]pyridazine- 8-carboxylate up 122-123 deg. 1H NMR (CDCl3) 5 1.38 (1H, t, J = 8 Hz), 2.12 (1H, s), 3.06 (2H, t, J = 8 Hz), 3.61 (1H, s), 5.43 (2H, s), 6.37 (1H, d, J = 5 Hz), 6.78 (1H, d, J = 5 Hz), 7.93 (1H, t, J = 1 Hz), 8.57 (1H, d, J = 1 Hz), 8.78 (1H, d, J = 1 Hz). MS (ES1+): m/z 432,434 (M + H). Example 430 2-(2-{2-[7-ethyl-2-methyl-4-(5-melhyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3- yl]ethoxy}ethoxy)ethyl acetate 1H-NMR (CDCl3) 5 1.37 (1H, t ,J = 7 Hz), 2.05 (1H, s), 2.42 (1H, s), 2.59 (1H, s), 2.75 (2H, m), 3.00 (2H, q, J = 7 Hz), 3.39-3.48 (4H, m), 3.54 (2H, m), 3.63 (2H, m), 4.16 (2H, m), 5.86 (1H, d, J = 5 Hz), 6.52 (1H, d, J = 5 Hz), 7.50 (1H, m), 8.43 (lH,m), 8.52 (lH,m). Example 431 ethyl (2E)-4-[4-(3-cyanophenyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]-2- butenoate 1H-NMR (CDCl3) 6 1.27 (1H, t, J = 7 Hz), 1.36 (1H, t, J = 7 Hz), 2.49 (1H, s), 3.02 (2H, q, J = 7 Hz), 3.30 (2H, m), 4.16 (2H, q, J = 7 Hz), 5.58 (1H, d, J = 16 Hz), 5.90 (1H, d, J = 5 Hz), 6.56 (1H, d, J = 5 Hz), 6.97 (1H, dt, J = 7 and 16 Hz), 7.58 (2H, m), 7.65 (1H, s), 7.75 (1H, m). Example 432 ethyl 4-[4-(5-bromo-3-pyridinyi)-7-elhyl-2-(methoxymethy])pyrrolo[l,2-b]pyridazin-3- yljbutanoate 1H NMR (300 MHz, CDC13) 6 1.23 (1H, t, J= 7 Hz), 1.37 (1H, t, J= 7 Hz), 1.65-1.78 (2H, m), 2.23 (2H, t, J= 7 Hz), 2.54-2.72 (2H, m), 3.04 (2H, q, J= 7 Hz), 3.46 (1H, s), 4.06 (2H, q, J= 7 Hz), 4.66 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.89 (1H, m), 8.55 (1H, d, J= 2 Hz), 8.77 (1H, d, J= 2 Hz). MS (ES1+): m/z 460 462. Example 433 ethyl 4-(2-chloro-4-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazine-3-carboxylate1H NMR (CDCl3) 6 0.99 (1H, t, J = 8 Hz), 1.38 (1H, t, J = 8 Hz), 2.63 (1H, s), 3.05 (2H, q, J = 8 Hz), 4.07 (2H, q, J = 8 Hz), 6.27 (1H, d, J = 5 Hz), 6.70 (1H, d, J = 5 Hz), 7.30 (1H, dd, J = 5,1 Hz), 7.41 (1H, br s), 8.49 (1H, d, J = 5 Hz). MS (ES1+): m/z 344 (M + H). The following compound(s) was(were) obtained in a similar manner to that of Example 76. Example 434 4-[4-(2-chloro-4-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]butanoicacid1H NMR (CDCl3) 5 1.37 (1H, t, J= 7 Hz), 1.72-1.84 (2H, m), 2.33 (2H, t, J= 7 Hz), 2.47-2.57 (2H, m), 2.58 (1H, s), 3.03 (2H, q, J= 7 Hz), 5.88 (1H, d, J= 4 Hz), 6.53 (1H, d, J= 4 Hz), 7.27 (1H, m), 7.38 (1H, s), 8.53 (1H, d, J= 5 Hz). MS (ESI-): m/z 356, MS (ES1+): m/z 358. Example 435 3-[4-(2-chloro-4-pyridinyl)-7-ethyl-2-methylpyrrolo[l ,2-b]pyridazin-3-yl]propanoic acid 1H NMR (CDCl3) 6 137 (1H, t, J= 7 Hz), 2.36-2.47 (2H, m), 2.58 (1H, s), 2.76-2.88 (2H, m), 3.03 (2H, q, J= 7 Hz), 5.89 (1H, d, J= 4 Hz), 6.55 (1H, d, J= 4 Hz), 7.25 (1H, d, J= 5 Hz), 7.35 (1H, s), 8.53 (1H, d, J= 5 Hz). Example 436 4-[4-(2-chloro-4-pyridiny])-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]butanoicacid1H NMR (CDCl3) 6 1.24 (1H, t, J= 7 Hz), 1.30-1.42 (2H, m), 1.35 (9H, s), 1.63-1.76 (2H, m), 2.22-2.37 (4H, m), 3.93 (1H, d, J= 17 Hz), 4.12 (2H, q, J= 7 Hz), 4.29 (1H, d, J= 17 Hz), 7.22 (2H, d, J= 8 Hz), 7.26-7.36 (4H, m), 7.50 (1H, s), 8.42 (lH,d,J=z). MS (ESF): m/z 418, MS (ESI+): m/z 420. Example 437 3-[4-(2-chloro-4-pyridinyl)-7-ethyl-2-phenylpyrrolo[l,2'b]pyridazin-3-yl]propanoicacid1H NMR (CDCl3) 6 1.36 (1H, t, J= 7 Hz), 2.06 (2H, t, J= 7 Hz), 2.78 (2H, t, J= 7 Hz), 3.04 (2H, q, J= 7 Hz), 5.99 (1H, d, J= 4 Hz), 6.67 (1H, d, J= 4 Hz), 7.28 (1H, d, J= 5 Hz), 7.41 (1H, s), 7.45-7.55 (, m), 8.53 (1H, d, J= 5 Hz). MS (ESf): m/z 404, MS (ESI+): m/z 406. Example 438 5-[2-benzyl-4-(2-chloro-4-pyridinyl)-7-ethylpyrrolo[l,2-b]pyridazin-3-yl]pentanoicacid NMR (CDCl3) 6 1.16-1.32 (2H, m), 1.39 (1H, t, J= 7 Hz), 1.38-1.53 (2H, m), 2.15 (2H, 1, J= 7 Hz), 2.30-2.40 (2H, m), 3.06 (2H, q, J= 7 Hz), 4.21 (2H, s), 5.88 (1H, d, J= 4 Hz), 6.58 (lH,d, J= 4 Hz), 7.18-7.35 (7H,m), 8.49 (1H, d, J= 5 Hz). MS (ESI-): m/z 446, MS (ESf): m/z 448. Example 439 {2-[7-ethyl-2-methyl-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]ethoxy}acetic acid 1H NMR (CDCh) 5 137 (1H, t, J= 7 Hz), 2.44 (1H, s), 2.59 (1H, s), 2.74-2.92 (2H, m),3.02(2H,q,J=7Hz),3.54-3.66(2H,m),3.93(2H,m),5.82(lH,d,J=4Hz), 6.53 (1H, d, J= 4 Hz), 7.63 (1H, s), 8.52 (1H, s), 8.56 (1H, s). F.-x ample 440 {2-[4-(2-chloro-4-pyridinyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]ethoxy}acetic acid ,H NMR (CDCl3) 6 137 (1H, (, J= 7 Hz), 2.80 (2H, t, J= 7 Hz), 3.03 (2H, q, J= 7 Hz), 3.20 (2H, t, J= 7 Hz), 3.72 (1H, s), 6.01 (1H, d, .1= 4 Hz), 6.67 (1H, d, J= 4 Hz), 7.42 (1H, d, J= 5 Hz), 7.45-7.60 (6H, m), 8.57 (J H, d, J= 5 Hz). Example 441 [4-(5-bromo-3-pyridiny])-7-e{hyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]aceticacid 1H NMR (CDC1.0 6 1 -37 (1H, t, J= 7 Hz), 2.55 (1H, s), 2.97-3.10 (2H, m), 3.30-3.62 (2H, m), 5.97 (1H, m), 6.57 (1H, m), 8.03 (1H, s), 8.69 (1H, s), 8.77 (1H, s). MS(ESl+):m/z374 376. Example 442 3-{7-ethyl-4-(5-methyl-3-pyridinyl)-2-[(4-pyridinylmethoxy)methyl]pyrro]o[l,2-b]pyridazin-3-yl}propanoic acid 1H NMR (CDCfe) 6 1.38 (1H, t, J= 7 Hz), 2.33-2.50 (2H, m), 2.42 (1H, s), 2.80-3.00 (2H, m), 3.06 (2H, q, J= 7 Hz), 4.72 (2H, s), 4.83 (2H, s), 5.92 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.36 (2H, d, J= 7 Hz), 7.55 (1H, s), 8.41 (1H, s), 8.44 (2H, d,J=7Hz),8.53(lH,s). MS(ESl+):m/z429 431. Example 443 3-{7-ethyl-4-(5-methyl-3-pyridinyl)-2-[(2-pyrazinylmethoxy)methyl]pyrrolo[l,2-b]pyridazin-3-yl}propanoic acid 1H NMR (CDC13) 6 1.38 (1H, t, J= 7 Hz), 2.42 (1H, s), 2.40-2.55 (2H, m), 2.83-3.12 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.84 (2H, s), 4.91 (2H, m), 5.92 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.57 (1H, s), 8.42 (1H, s), 8.48-8.55 (1H, m), 8.76 (1H, s). MS (ES1+): m/z 432. Example 444 3-{7-ethyl-4-(5-methyl-3-pyridinyl)-2-[(2-pyridinylmethoxy)methyl]pyrrolo[l,2- b]pyridazin-3-yl}propanoic acid 1H NMR (CDCl3) 6 1.37 (1H, t, J= 7 Hz), 2.43 (1H, s), 2.50-2.60 (2H, m), 2.88-3.05 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.81 (2H, s), 4.87 (2H, s), 5.82 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.27 (1H, m), 7.48 (1H, d, J= 8 Hz), 7.56 (1H, s), 7.77 (1H, t, J= 8 Hz), 8.43 (1H, s), 8.54 (2H, m). Example 445 4-{7-elhyl-4-(5-methyl-3-pyridinyl)-2-[(4-pyridinylinelhoxy)melhyl]pyrro]o[l,2-b]pyridazin-3-yl}butanoic acid 1H NMR (CDCl3) 6 1.40 (1H, t, J= 7 Hz), 1.70-1.85 (2H, m), 2.16-2.31 (2H, m), 2.44 (1H, s), 2.53-2.83 (2H, m), 3.05 (2H, q, J= 7 Hz), 4.72 (2H, s), 4.83-4.98 (2H, m), 5.92 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.30 (2H, d, J= 7 Hz), 7.57 (1H, s), 8.38-8.55 (4H,m). MS (ESI-): m/z 443, MS (ESI+): m/z 445. Example 446 5-{4-(5-bromo-3-pyridinyl)-7-ethyl-2-[(4-pyridiny]melhoxy)methyl]pyrrolo[l,2- b]pyridazin-3-yl}pentanoic acid 1H NMR (CDCl3) 5 1.38 (1H, t, J= 7 Hz), 1.40-1.63 (4H, m), 2.20 (2H, t, J= 7 Hz), 2.52-2.68 (2H, m), 3.04 (2H, q, J= 7 Hz), 4.69 (2H, s), 4.78 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.35 (2H, d, J= 6 Hz), 7.88 (1H, m), 8.54 (2H, d, J= 6 Hz), 8.55 (1H, m), 8.79 (1H, m). Example 447 5-{4-(5-bromo-3-pyridinyl)-7-ethy]-2-[(3-pyridiny]methoxy)methyl]pyrrolo[l,2-b]pyridazin-3-yl}pentanoic acid 1H NMR (CDC13) 6 1.38 (1H, t, J= 7 Hz), 1.40-1.62 (4H, m), 2.17 (2H, t, J= 7 Hz), 2.50-2.67 (2H, m), 3.04 (2H, q, J= 7 Hz), 4.69 (2H, s), 4.76 (2H, s), 5.92 (1H, d, J= 4 Hz), 6.61 (1H, d, i= 4 Hz), 7.32-7.38 (1H, m), 7.77 (1H, d, J= 8 Hz), 7.88 (1H, m), 8.55 (2H, m), 8.65 (1H, m), 8.78 (1H, m). MS (ESI-): m/z 521 523, MS (ESI+): m/z 523 525. Example 448 5-{4-(5-bromo-3-pyridinyl)-7-ethyl-2-[(2-pyridinylmethoxy)methyl]pyrrolo[l,2- b]pyridazin-3-yl}penlanoic acid 1H NMR (CDCl3) 6 1.37 (1H, t, J= 7 Hz), 1.48-1.67 (4H, m), 2.26 (2H, t, J= 7 Hz), 2.53-2.75 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.82 (2H, s), 4.83 (2H, s), 5.90 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.26-7.34 (1H, m), 7.53 (1H, d, J= 8 Hz), 7.75- 7.83 (1H, m), 7.87 (1H, m), 8.55 (] H, d, J= 2 Hz), 8.62 (1H, m), 8.77 (1H, d, J= 2 Hz). MS(ESI+):m/z523 525. Example 449 5-{4-(5-bromo-3-pyridinyl)-7-ethyl-2-[(2-pyrazinylmethoxy)methy]]pynolo[J,2-b]pyridazin-3-yl}pentanoic acid 1H NMR (CDC13) 5 1 -38 (1H51, J= 7 Hz), 1.45-1.64 (4H, m), 2.23 (2H, t, J= 7 Hz), 2.53-2.72 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.83 (2H, s), 4.87 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.88 (1H, m), 8.53 (1H, m), 8.77 (2H, m). MS (ESI˚): m/z 522 524, MS (ESI+): m/z 524 526. Example 450 4-{4-(5-bromo-3-pyridinyl)-7-ethyl-2-[(4-pyridinylmethoxy)methyl]pyrrolo[l,2-b]pyridazin-3-yl}butanoic acid 1H NMR (CDCl3) 6 1.39 (1H, t, J= 7 Hz), 1.69-1.84 (2H, m), 2.27 (2H, t, J= 7 Hz), 2.56-2.80 (2H, m), 3.02 (2H, q, J= 7 Hz), 4.73 (2H, s), 4.92 (2H, m), 5.94 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.31 (2H, d, J= 6 Hz), 7.90 (1H, m), 8.46 (2H, d, J= 6 Hz), 8.57 (1H, d, J= 2 Hz), 8.78 (1H, d, J= 2 Hz). MS (ESI-): m/z 507 509, MS (ES1+): m/z 509 511. Example 451 4-{4-(5-bromo-3-pyridinyl)-7-ethyl-2-[(3-pyridinylmethoxy)methyl]pyrrolo[l,2-b]pyridazin-3-yl}butanoic acid NMR (CDCl3) 6 1.38 (1H, t, J= 7 Hz), 1.66-1.83 (2H, m), 2.26 (2H, t, J= 7 Hz), 2.53-2.77 (2H, m), 3.04 (2H, q, J= 7 Hz), 4.71 (2H, s), 4.86 (2H, m), 5.92 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.33 (1H, m), 7.78 (1H, d, J= 8 Hz), 7.90 (1H, m), 8.50 (1H, m), 8.56 (1H, d, J= 2 Hz), 8.60 (1H, s), 8.78 (1H, d, J= 2 Hz). MS(ES]+):m/z509 511. Example 452 4-{4-(5-bromo-3-pyridinyl)-7-ethyl-2-[(2-pyridinylmelhoxy)methyl]pyrroIo[l,2-b]pyridazin-3-yl}butanoic acid f 1H NMR (CDCl3) 5 1.37 (1H, t, J= 7 Hz), 1.70-1.85 (2H, m), 2.23-2.34 (2H, m), 2.57-2.76 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.81 (2H, s), 4.90 (2H, m), 5.91 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.28 (1H, m), 7.49 (1H, d, J= 7 Hz), 7.77 (1H, t, J= 8 Hz), 7.88 (1H, m), 8.55 (1H, d, J= 2 Hz), 8.57 (1H, m), 8.74 (1H, d, J= 2 Hz). MS(ESl+):m/z509 511. Example 453 4-{4-(5-bromo-3-pyridinyl)-2-[(cyclopropylmethoxy)methyl]-7-ethylpynolo[l,2-,]pyridazin-3-yl}butanoic acid 1H NMR (CDC13) 6 0.22 (2H, m), 0.57 (2H, m), 1.07-1.22 (1H, m), 1.37 (1H, t, J= 7 Hz), 1.72-1.87 (2H, m), 2.28 (2H, t, J= 7 Hz), 2.58-2.77 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.41 (2H, d, J= 7 Hz), 4.72 (2H, s), 5.92 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 7.93 (1H, m), 8.56 (1H, d, J= 2 Hz), 8.77 (1H, d, J= 2 Hz). MS (ESI'): m/z 470 472, MS (ESI+): m/z 472 474. Example 454 4-{4-(5-bromo-3-pyridinyl)-7-ethyl-2-[(2-pyrazinylmethoxy)methyl]pyrrolo[l,2-b]pyridazin-3-yl}butanoic acid 1H NMR (CDCl3) 6 1.38 (1H, t, J= 7 Hz), 1.68-1.83 (2H, m), 2.27 (2H, t, J= 7 Hz), 2.56-2.78 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.84 (2H, s), 4.92 (2H, m), 5.94 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.91 (1H, m), 8.51 (2H, m), 8.56 (1H, d, J= 2 Hz), 8.76 (2H,m). MS (ESI'): m/z 508 510, MS (ES1+): m/z 510 512. Example 455 3-{4-(5-bromo-3-pyridinyl)-7-ethyl-2-[(4-pyridinylmelhoxy)methyl]pyrrolo[l,2-b]pyridazin-3-yl} propanoic acid NMR (CDCl3) 5 1.39 (1H, t, J= 7 Hz), 2.38 (2H, t, J= 7 Hz), 2.83-2.98 (2H, m), 3.07 (2H, q, J= 7 Hz), 4.74 (2H, s), 4.83 (2H, s), 5.95 (1H, d, J= 4 Hz), 6.65 (1H, d, J= 4 Hz), 7.38 (2H, d, J= 6 Hz), 7.88 (1H, s), 8.43 (2H, d, J= 6 Hz), 8.55 (1H, s),8.78(lH,s). MS (ESI'): m/z 493 495, MS (ESI+): m/z 495 497. Example 456 4-{4-(5-bi-omo-3-pyriclinyJ)-7-ethyl-2-[(2-hydroxyethoxy)methyl]pyrro]o[l,2- b]pyridazin-3-yl}butanoic acid 1H NMR (CDCl3) 5 1.37 (1H, t, J= 7 Hz), 1.68-1.83 (2H, m), 2.28 (2H, t, J= 7 Hz), 2.53-2.76 (2H, m), 3.02 (2H, q, J= 7 Hz), 3.75 (2H, m), 3.79 (2H, m), 4.78 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.90 (1H, s), 8.56 (1H, s), 8.78 (JH, s). MS (ESI'): m/z 460 462, MS (ESI+): m/z 462 464. Example 457 3-[2-[(cyclohexylmethoxy)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pynolo[l,2-b]pyridazin-3-yl]propanoic acid 1H NMR (CDCl3) 6 0.88-1.06 (2H, m), 1.10-1.36 (1H, m), 1.37 (1H, t, J= 7 Hz), 1.58-1.85 (6H, m), 2.42 (1H, s), 2.48-2.60 (2H, m), 2.80-3.02 (2H, m), 3.04 (2H, q, J= 7 Hz), 3.39 (2H, d, J= 7 Hz), 4.67 (2H, m), 5.89 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.57 (1H, s), 8.42 (1H, s), 8.53 (1H, s). MS (ESI˚): m/z 434, MS (ES1+): m/z 436. Example 458 3-{4-(5-bromo-3-pyridinyl)-2-[(cyclohexy]methoxy)methyl]-7-ethylpyrrolo[l,2-b]pyridazin-3-yl}propanoic acid JH NMR (CDCl3) 6 0.88-1.05 (2H, m), 1.10-1.36 (1H,m), 1.37 (1H, t, J= 7 Hz), 1.56-1.83 (6H, m), 2.51 (2H, t, J= 7 Hz), 2.80-3.07 (2H, m), 3.06 (2H, q, J= 7 Hz), 3.37 (2H, d, J= 7 Hz), 4.67 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.89 (1H, m), 8.55 (1H, s), 8.79 (1H, s). MS (ESI-): m/z 498 500, MS (ESI+): m/z 500 502. Example 459 4-{4-(5-bromo-3-pyridinyl)-2-[(cyclohexylmethoxy)methyl]-7-ethylpyrrolo[l,2-b]pyridazin-3-yl}butanoic acid 1H NMR (CDCl3) 6 0.86-1.03 (2H, m), 1.10-1.35 (1H, m), 1.37 (1H, t, J= 7 Hz), 1.60-1.82 (8H, m), 2.28 (2H, t, J= 7 Hz), 2.55-2.76 (2H, m), 3.05 (2H, q, J= 7 Hz), 3.36 (2H, d, J= 7 Hz), 4.67 (2H, s), 5.92 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.91 (1H, m), 8.55 (1H, d, J= 2 Hz), 8.76 (1H, d, J= 2 Hz). MS (ESI'): m/z 512 514, MS (ES1+): m/z 514 516. Example 460 4-[2-[(cyclopropylmethoxy)methyl]-7-elhyl-4-(5-methyI-3-pyridinyJ)pyrrolo[l,2-b]pyridazin-3-yl]butanoic acid 1H NMR (CDC13) 6 0.22-0.32 (2H,m), 0.55-0.63 (2H,m), 1.10-1.22 (lH,m), 1.37 (1H, t, J= 7 Hz), 1.73-1.86 (2H, m), 2.20-2.35 (2H, m), 2.46 (1H, s), 2.55-2.86 (2H, m), 3.04 (2H, q, J= 7 Hz), 3.43 (2H, d, J= 7 Hz), 4.70-4.85 (2H, m), 5.88 (1H, d, J= 4 Hz), 6.57 (1H, d, J= 4 Hz), 7.62 (1H, s), 8.42 (1H, s), 8.46 (1H, s). MS (ESI+): m/z 408. Example 461 3-[2-[(cyclopropylmethoxy)methyl]-7-ethyl-4-(5-methyl-3-pyridinyl)pyrro]o[l,2-b]pyridazin-3-yl]propanoic acid 1H NMR (CDC13) 5 0.23-0.35 (2H, m), 0.54-0.65 (2H, m), 1.08-1.24 (1H, m), 1.37 (1H, t, J= 7 Hz), 2.43 (1H, s), 2.50-2.65 (2H, m), 2.70-3.05 (2H, m), 3.04 (2H, q, J= 7 Hz), 3.44 (2H, d, J= 7 Hz), 4.74 (2H, s), 5.89 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.56 (1H, s), 8.42 (1H, s), 8.53 (1H, s). MS (ESI-): m/z 392, MS (ESI+): m/z 394. Example 462 3-{4-(5-bromo-3-pyridinyl)-7-ethyl-2-[(2-methoxyethoxy)methyl]pyrrolo[l,2-b]pyridazin-3-yl}propanoic acid 1H NMR (CDC13) 6 1.37 (1H, t, J= 7 Hz), 2.48-2.62 (2H, m), 2.83-3.02 (2H, m), 3.02 (2H, q, J= 7 Hz), 3.37 (1H, s), 3.60 (2H, m), 3.73 (2H, m), 4.75 (2H, s), 5.92 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.89 (1H, m), 8.55 (1H, d, J= 2 Hz), 8.78 (1H, d,J=2Hz). MS (ESI-): m/z 460 462, MS (ES1+): m/z 462 464. Example 463 5-(4-(5-bromo-3-pyridinyl)-7-ethyl-2-{[(4-moiphoIinylcarbonyl)oxy]methyl}pyrrolo[l,2-b]pyridazin-3-yl)pentanoic acid 1H NMR (CDCl3) 6 1.37 (1H, 1, J= 7 Hz), 1.35-1.65 (4H, m), 2.23 (2H, t, J= 7 Hz), 2.40-2.56 (2H, m), 3.02 (2H, q, J= 7 Hz), 3.48-3.57 (4H, m), 3.60-3.78 (4H, m), 5.33 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.89 (1H, m), 8.56 (1H, d, J= 2 Hz), 8.79 (1H, d, J= 2 Hz). Example 464 5-[4-(5-bromo-3-pyridinyl)-2-({[(dimethylamino)carbonyl]oxy}methyl)-7-elhy]pyrrolo[l ,2-b]pyridazin-3-yl]pentanoic acid 1H NMR (CDCl3) 5 1.36 (1H, t, J= 7 Hz), 1.45-1.65 (4H, m), 2.22 (2H, t, J= 7 Hz), 2.42-257 (2H, m), 2.97 (6H, s), 3.03 (2H, q, J= 7 Hz), 5.30 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.89 (1H, s), 8.54 (1H, s), 8.78 (1H, s). MS(ESl+):m/z503 505. Example 465 5-(4-(5-bromo-3-pyridinyl)-7-ethyl-2-{[(l-pyrrolidinylcarbonyl)oxy]methyl}pyrrolo[l,2-b]pyridazin-3-yl)pentanoic acid 1H NMR (CDCl3) 5 1.36 (1H, t, J= 7 Hz), 1.40-1.63 (4H, m), 1.82-1.97 (4H, m), 2.23 (2H, t, J= 7 Hz), 2.43-2.58 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.37-3.52 (4H, m), 5.31 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 7.88 (1H, m), 8.54 (1H, d, J= 2 Hz), 8.78 (1H, d, J= 2 Hz). MS (ESI-): m/z 527 529, MS (ES1+): m/z 529 531. Example 466 5-{4-(5-bromo-3-pyridinyl)-7-ethyl-2- [({[methyl(phenyl)amino]carbonyl}oxy)methyl]pyrrolo[l,2-b]pyridazin-3-yl}penlanoic acid 1H NMR (CDCl3) 6 1.38 (1H, t, J= 7 Hz), 1.40-1.58 (4H, m), 2.18 (2H, t, J= 7 Hz), 2.32-2.53 (2H, m), 3.04 (2H, q, J= 7 Hz), 3.37 (1H, s), 5.36 (2H, s), 5.92 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.16-7.40 (, m), 7.87 (1H, s), 8.52 (1H, s), 8.79 (lH.s). Example 467 4-(4-(5-bromo-3-pyiidl3iyl)-7-ethyl-2-{[(4-morpholinylcarbonyr)oxy]melhyl}pyrrolo[l,2- b]pyiidazin-3-yI)butanoic acid 1H NMR (CDC13) 5 J .37 (1H, t, J= 7 Hz), J .65-1.84 (2H, m), 2.27 (2H, t, J= 7 Hz), 2.45-2.68 (2H, m), 3.04 (2H, q, J= 7 Hz), 3.53 (4H, m), 3.69 (4H, m), 5.36 (2H, s), 5.95(lH,d,J=4Hz),6.63(lH,d,J=4Hz),7.91 (lH,m), 8.55 (1H, d, J= 2 Hz), 8.78(lH,d,J=2Hz). Example 468 4-[4-(5-bromo-3-pyridinyl)-2-({[(dimethylamino)carbonyl]oxy}methyl)-7- ethylpyrrolo[l ,2-b]pyridazin-3-yl]butanoic acid 1H NMR (CDC13) 5 1.36 (1H, t, J= 7 Hz), 1.66-1.82 (2H, m), 2.27 (2H, t, J= 7 Hz), 2.46-2.68 (2H, m), 2.97 (6H, s), 3.04 (2H, q, J= 7 Hz), 5.33 (2H, s), 5.94 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.92 (1H, m), 8.56 (1H, d, J= 2 Hz), 8.78 (1H, d, J= 2 Hz). Example 469 3-[4-(5-bromo-3-pyridinyl)-2-({[(dimethylamino)carbonyl]oxy}methyl)-7-ethylpyrroIo[l ,2-b]pyridazin-3-yl]propanoic acid 1H NMR (CDC13) 6 1.36 (1H, t, J= 7 Hz), 2.45 (2H, t, J= 7 Hz), 2.82-2.96 (2H, m), 2.97 (6H, s), 3.03 (2H, q, J= 7 Hz), 5.33 (2H, s), 5.96 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.89 (1H, m), 8.55 (1H, d, J= 2 Hz), 8.78 (1H, d, J= 2 Hz). MS (ESI-): m/z 473 475, MS (ESI+): m/z 475 477. Example 470 5-{4-(5-bromo-3-pyridinyl)-2-[(l,l-dioxido-4-thiori-»orpholinyl)methy]]-7-ethylpyrrolo[l ,2-b]pyridazin-3-yl}pentanoic acid JH NMR (300 MHz, CDC13) 5 1.36 (1H, t, J = 7 Hz), 1.42-1.56 (4H, m), 2.26 (2H, l, J = 7 Hz), 2.48-2.61 (2H, m), 3.01 (2H, q, J = 7 Hz), 3.10 (4H, t, J = 6 Hz), 3.19 (4H, t, J = 6 Hz), 3.85 (2H, s), 5.92 (1H, d, J = 4 Hz), 6.61 (1H, d, J = 4 Hz), 7.89 (1H, dd, J = 2, 2 Hz), 8.56 (1H, d, J = 2 Hz), 8.78 (1H, d, J = 2 Hz). MS(m/z)550(M+H). Example 471 5-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(4-thiomO]pho]iny]melhy])pyrrolo[l,2-b]pyridazin- 3-y]]penlanoic acid 1H NMR (300 MHz, CDCl3) 6 ] .37 (1H, t, J = 7 Hz), ] .43-1.58 (4H, m), 2.24 (2H, t, J = 7 Hz), 2.49-2.61 (2H, m), 2.66 (4H, t, J = 4 Hz), 2.86 (4H, 1, J = 4 Hz), 3.02 (2H, q, J = 7 Hz), 3.68 (2H, s), 5.89 (1H, d, J = 5 Hz), 6.58 (1H, d, J = 5 Hz), 7.90 (lH,s), 8.56 (lH,s), 8.79 (lH,s). MS(m/z)518(M+H). Example 472 5-(4-(5-bromo-3-pyridinyI)-7-ethyl-2-{[4-(2-hydroxyethy])-l- piperazinyl]methyl}pyrrolo[l,2-b]pyridazin-3-y])pentanoicacid 1H NMR (300 MHz, CDCl3) 6 1.34 (1H, t, J = 7 Hz), 1.41-1.57 (4H, m), 2.21 (2H, t, J = 6 Hz), 2.43-2.57 (2H, m), 2.80-2.84 (4H, m), 2.91-3.00 (6H, m), 3.65 (2H, s), 3.83 (2H, m), 5.88 (1H, d, J = 5 Hz), 6.57 (1H, d, J = 5 Hz), 7.88 (1H, s), 8.55 (1H,s),8.77(lH,s). MS (m/z) 545 (M+H). Example 473 4-[4-(5-chloro-3-pyridinyl)-7-ethyl-2-(4-thiomorpholiny]melhy])pyrrolo[l,2-b]pyridazin-3-yl]butanoic acid 1H NMR (300 MHz, CDCl3) 6 1.37 (1H, t, J = 7 Hz), 1.72 (2H, tt, J = 7, 7 Hz), 2.26 (2H, t, J = 7 Hz), 2.53-2.68 (6H, m), 2.87-2.90 (4H, m), 3.02 (2H, q, J = 7 Hz), 3.72 (2H, s), 5.91 (1H, d, J = 4 Hz), 6.59 (1H, d, J = 4 Hz), 7.78 (1H, dd, J = 2,2 Hz), 8.52 (1H, d, J = 2 Hz), 8.68 (1H, d, J = 2 Hz). MS (m/z) 460 (M+H). Example 474 4-{4.(5-chloro-3-pyridinyl)-7-ethyl-2-[(4-pyridinyImethoxy)methy]]pyrrolo[l,2- b]pyridazin-3-yl}butanoic acid NMR (300 MHz, CDC13) § 1.38 (1H, t, J = 7 Hz), 1.73 (2H, tt, J = 7, 7 Hz), 2.25 (2H, t, J = 7 Hz), 2.57-2.73 (2H, m), 3.04 (2H, q, J = 7 Hz), 4.72 (2H, s), 4.89 (2H, s), 5.93 (1H, d, J =5 Hz), 6.63 (1H, d, J =5 Hz), 7.31 (2H, d, J = 6 Hz), 7.76 (1H, dd, J = 2,2 Hz), 8.46 (2H, d, J = 6 Hz), 8.53 (1H, d, J = 2 Hz), 8.67 (1H, d, J = 2 Hz). MS (m/z) 465 (M+H). Example 475 4-[4-(5-chloro-3-pyridinyl)-7-ethy]-2-(4-morpholiny]methyl)pyrrolo[l,2-b]pyridazin-3- yl]butanoic acid 1H NMR (300 MHz, CDC13) 6 1.37 (1H, I, J = 7 Hz), 1.73 (2H, tl, J = 7, 7 Hz), 2.26 (2H, l, J = 7 Hz), 2.54-2.72 (6H, m), 3.03 (2H, q, J = 7 Hz), 3.66-3.73 (6H, m), 5.90 (1H, d, J = 4 Hz), 6.59 (1H, d, J = 4 Hz), 7.79 (1H, s), 8.53 (1H, s), 8.67 (JH, s). MS (m/z) 443 (M+H). Example 476 5-{4-(5-chloro-3-pyridinyl)-2-[(cyc]opropylmethoxy)methyl]-7-ethylpynolo[l,2-b]pyridazin-3-yl}pentanoic acid 1H NMR (300 MHz, CDC13) 8 0.24 (2H, dt, J = 7, 7 Hz), 0.57 (2H, dt, J = 7, 7 Hz), 1.07-1.17 (lH,m), 1.38 (1H, t, J = 7 Hz), 1.45-1.61 (4H,m), 2.23 (2H, 1, J = 7 Hz), 2.52-2.66 (2H, m), 3.02 (2H, q, J = 7 Hz), 3.41 (2H, d, J = 7 Hz), 4.70 (2H, s), 5.90 (1H, d, J = 4 Hz), 6.59 (1H, d, J = 4 Hz), 7.74 (1H, dd, J = 2, 2 Hz), 8.52 (1H, d, J = 2 Hz), 8.68 (1H, d, J = 2 Hz). MS (m/z) 442 (M+H). Example 477 4-{4-(5-chloro-3-pyridinyl)-2-[(cyclopropylmethoxy)methyl]-7-ethy3pyrrolo[l,2-b]pyridazin-3-yl}butanoic acid 1H NMR (300 MHz, CDCl3) 8 0.23 (2H, dt, J = 6, 6 Hz), 0.56 (2H, dt, J = 6, 6 Hz), 1.05-1.17 (1H, m), 1.37 (1H, t, J = 7 Hz), 1.75 (2H, tt, J = 7, 7 Hz), 2.28 (2H, t, J = 7 Hz), 2.57-2.70 (2H, m), 3.03 (2H, q, J = 7 Hz), 3.42 (2H, d, J = 7 Hz), 4.73 (2H, s), 5.91 (1H, d, J = 5 Hz), 6.60 (1H, d, J = 5 Hz), 7.77 (1H, dd, J = 2,2 Hz), 8.52 (1H, d, J = 2 Hz), 8.66 (1H, d, J = 2 Hz). MS (m/z) 428 (M+H). Example 478 5-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(isobutoxymethyl)pynolo[l,2-b]pyridazin-3- yl]pentanoic acid 1H NMR (300 MHz, CDC13) 5 0.93 (6H, d, J = 7 Hz), 1.37 (1H, t, J = 7 Hz), 1.42- 1.59 (4H, m), 1.92 (1H, qt, J = 7,7 Hz), 2.24 (2H, 1, J = 7 Hz), 2.48-2.69 (2H, m), 3.03 (2H, q, J = 7 Hz), 3.33 (2H, d, J = 7 Hz), 4.66 (2H, s), 5.91 (1H, d, J = 4 Hz), 6.59 (1H, d, J = 4 Hz), 7.90 (1H, dd, J = 2,2 Hz), 8.56 (1H, d, J = 2 Hz), 8.77 (1H, d,J = 2Hz). MS(m/z)489(M+H). Example 479 3-[4-(5-ch]oro-3-pyridinyl)-7-ethyl-2-(isobutoxymelhyl)pyrrolo[l,2-b]pyridazin-3-y]]propanoic acid NMR (300 MHz, CDGh) 5 0.92 (6H, d, J = 7 Hz), 1.37 (1H, 1, J = 7 Hz), 1.91 (1H, qt, J = 7, 7 Hz), 2.49 (2H, t, J = 8 Hz), 2.82-2.98 (2H, m), 3.03 (2H, q, J = 7 Hz), 3.35 (2H, d, J = 7 Hz), 4.69 (2H, s), 5.92 (1H, d, J = 4 Hz), 6.61 (1H, d, J = 4 Hz), 7.72 (1H, dd, J = 2, 2 Hz), 8.51 (1H, d, J = 2 Hz), 8.69 (1H, d, J = 2 Hz). MS (m/z) 416 (M+H). Example 480 3-[4-(5-bromo-3-pyridinyI)-7-ethyl-2-(4-moipholinylmethyl)pyrroIo[l,2-b]pyridazin-3-yl]propanoic acid 1H NMR (300 MHz, CDC13) 5 1.36 (1H, 1, J = 7 Hz), 2.55 (2H, t, J = 8 Hz), 2.66 (4H, br s), 2.79-2.97 (2H, m), 3.02 (2H, q, J = 7 Hz), 3.70-3.74 (6H, m), 5.92 (1H, d, J = 4 Hz), 6.61 (1H, d, J = 4 Hz), 7.90 (1H, dd, J = 2, 2 Hz), 8.55 (1H, d, J = 2 Hz), 8.79(lH,d,J = 2Hz). MS (m/z) 474 (M+H). Example 481 4-[4-(5-bromo-3-pyridinyl)-7-e(hyl-2-(4-moipholinylmethyl)pyrrolo[l,2-b]pyridazin-3- yl]butanoic acid 1H NMR (300 MHz, CDC13) 6 1.36 (1H, 1, J = 7 Hz), 1.73 (2H, tt, J = 7, 7 Hz), 2.26 (2H, t, J = 7 Hz), 2.57-2.70 (6H,m), 3.02 (2H, q, J = 7 Hz), 3.69 (6H, m), 5.90 (1H, d, J = 4 Hz), 6.58 (1H, d, J = 4 Hz), 7.93 (1H, dd, J = 2, 2 Hz), 8.57 (1H, d, J = 2Hz),8.77(lH,d,J = 2Hz). MS (m/z) 488 (M+H). Example 482 4-{4-(5-ch]oro-3-pyricliny])-2-[(cyclopropylamino)methy]]-7-cthy]pyrrolo[l,2-b]pyridazin-3-yl}butanoic acid 1H NMR (300 MHz, CDC13) 6 0.54-0.60 (2H, m), 0.74-0.79 (2H, m), 1.38 (1H, t, J = 7 Hz), 1.65 (2H, tt, J = 6, 6 Hz), 2.21 (2H, t, J = 6 Hz), 2.45-2.55 (2H, m), 3.03 (2H, q, J = 7 Hz), 4.30 (2H, s), 5.04 (1H, br s), 5.93 (1H, d, J = 5 Hz), 6.60 (1H, d, J = 5 Hz), 7.73 (1H, dd, J = 2,2 Hz), 8.52 (1H, d, J = 2 Hz), 8.69 (1H, d, J = 2 Hz). MS (m/z) 413 (M+H). Example 483 5-(4-(5-bromo-3-pyridinyl)-7-ethyl-2-{[(2-phenoxyethyl)amino]methyl}pyrrolo[l,2-b]pyridazin-3-yl)pentanoic acid 1H NMR (300 MHz, CDCl3) 6 1.36 (1H, t, J = 7 Hz), 1.42-1.56 (4H, m), 2.22 (2H, br s), 2.34-2.48 (2H, m), 3.03 (2H, q, J = 7 Hz), 3.38-3.43 (2H, br s), 4.23-4.50 (4H, m), 5.93 (1H, d, J = 4 Hz), 6.60 (1H, d, J = 4 Hz), 6.89-6.97 (1H, m), 7.23-7.30 (2H, m), 7.85 (1H, s), 8.52 (1H, s), 8.78 (1H, s). MS (m/z) 552 (M+H). Example 484 5-(4-(5-bromo-3-pyridinyl)-7-ethyl-2-{[(2- hydroxyethyl)(methyl)amino]methyl}pyrrolo[l,2-b]pyridazin-3-yl)pentanoic acid 1H NMR (300 MHz, CDC13) 6 1.36 (1H, t, J = 7 Hz), 1.34-1.54 (4H, m), 2.15-2.26 (2H, m), 2.33-2.52 (2H, m), 2.98 (2H, q, J = 7 Hz), 3.16 (1H, s), 3.59-3.72 (2H, m), 3.99-4.10 (2H, m), 4.70 (2H, s), 5.94 (1H, d, J = 4 Hz), 6.59 (1H, d, J = 4 Hz), 7.85 (1H, s), 8.51 (1H, s), 8.73 (1H, s). MS (m/z) 490 (M+H). Example 485 5-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(l-piperidinylmethyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid 1H NMR (300 MHz, CDCl3) 6 1.36 (1H, t, J = 7 Hz), 1.39-1.51 (6H,m), 1.62-1.71 (4H, m), 2.19 (2H, I, J = 6 Hz), 2.52-2.65 (2H, m), 2.78-2.91 (4H, m), 3.10 (2H, q, J = 7 Hz), 3.65 (2H, s), 5.89 (1H, d, J = 5 Hz), 6.58 (1H, d, J = 5 Hz), 7.88 (JH, s), 8.55 (lH,s), 8.76 (lH,s). MS(m/z)5()0(M+H). Example 486 3-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(4-lhiomoq')holinylmethyl)pyrrolo[l,2-b]pyridazin-3-yl]propanoic acid ]U NMR (300 MHz, CDCl3) 6 1.37 (1H, t, J = 7 Hz), 2.52 (2H, t, J = 8 Hz), 2.68 (4H, t, J = 5 Hz), 2.81-2.95 (6H, m), 3.02 (2H, q, J = 7 Hz), 3.74 (2H, s), 5.92 (1H, d, J = 5 Hz), 6.61 (1H, d, J = 5 Hz), 7.89 (1H, dd, J = 2,2 Hz), 8.55 (1H, d, J = 2 Hz), 8.79(lH,d,J = 2Hz). MS(m/z)490(M+H). Example 487 3-(4-(5-bromo-3-pyridinyl)-7-ethyl-2-{[4-(2-hydroxyethyl)-l-piperazinyl]methyl}pyrrolo[l,2-b]pyridazin-3-yl)propanoic acid 1H NMR (300 MHz, DMSO-d6) 5 1.32 (1H, t, J = 7 Hz), 2.40-2.56 (12H, m), 2.58-2.65 (2H, m), 2.94 (2H, q, J = 7 Hz), 3.52 (2H, t, J = 5 Hz), 3.67 (2H, s), 5.83 (1H, d, J = 5 Hz), 6.62 (1H, d, J = 5 Hz), 8.25 (1H, dd, J = 2,2 Hz), 8.63 (1H, d, J = 2 Hz),8.86(lH,d,J = 2Hz). MS (m/z) 517 (M+H). Example 488 4-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(isobutoxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]butanoic acid 1H NMR (300 MHz, CDC13) 8 0.91 (6H, d, J = 7 Hz), 1.37 (1H, t, J = 7 Hz), 1.74 (2H, tt, J = 8, 8 Hz), 1.91 (1H, qt, J = 7,7 Hz), 2.27 (2H, t, J = 8 Hz), 2.56-2.73 (2H, m), 3.03 (2H, q, J = 7 Hz), 3.33 (2H, d, J = 7 Hz), 4.68 (2H, s), 5.92 (1H, d, J = 5 Hz), 6.60 (1H, d, J = 5 Hz), 7.92 (1H, dd, J = 7, 7 Hz), 8.56 (1H, d, J = 2 Hz), 8.77(lH,d,J=2Hz). MS (m/z) 475 (M+H). Example 489 5-[2-{[2-(benzylamino)-2-oxoethoxy]methyl}-7-ethyl-4-(5-methyl-3-pyridiny])pyrrolo[l ,2-b]pyridazin-3-y]]penlanoic acid 1H NMR (CDCl3) 6 1 -33 (1H, t, J= 7 Hz), 1.39-1.60 (4H, m), 2.15 (2H, t, J= 7 Hz), 2.42 (1H, s), 2.40-2.58 (2H, m), 2.95 (2H, q, J= 7 Hz), 4.19 (2H, s), 4.50 (2H, d, J= 7 Hz), 4.75 (2H, m), 5.91 (1H, d, J= 4 Hz), 6.59 (1H, d, J= 4 Hz), 7.07 (1H, br), 7.22-7.34 (, m), 7.54 (1H, s), 8.40 (1H, s), 8.53 (1H, s). MS (ESI): m/z 513, MS (ESI+): m/z 515. Example 490 5-(7-ethyl-4-(5-methyl-3-pyridinyl)-2-{[(phenylsulfonyl)amino]methyl}pyrrolo[l,2-b]pyridazin-3-yl)pentanoic acid 1H NMR (CDCb) 6 1.36 (1H, t, J= 7 Hz), 1.23-1.60 (4H, m), 2.19 (2H, t, J= 7 Hz), 2.28-2.46 (2H, m), 2.42 (1H, s), 2.97 (2H, q, J= 7 Hz), 4.37 (2H, m), 5.89 (1H, d, J= 4 Hz), 5.90 (1H, m), 6.57 (1H, d, J= 4 Hz), 7.42-7.53 (4H, m), 7.90 (2H, d, J= 8 Hz), 8.34 (1H, s), 8.53 (1H, s). MS (ESI): m/z 505, MS (ESI+): m/z 507. Example 491 5-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(l-pyrrolidinylmethyl)pyrrolo[l,2-b]pyridazin-3-yl]penlanoic acid 1H NMR (300 MHz, CDCl3) 6 1.35 (1H, t, J = 7 Hz), 1.39-1.57 (4H, m), 1.79-1.88 (4H, m), 2.18 (2H, t, J = 7 Hz), 2.84-2.89 (6H, m), 3.00 (2H, q, J = 7 Hz), 3.89- 4.02 (2H, m), 5.88 (1H, d, J = 5 Hz), 6.56 (1H, d, J = 5 Hz), 7.87 (1H, s), 8.55 (1H,S),8.75(1H,S). MS (m/z) 486 (M+H). Example 492 3-[4-(3-chlorophenyl)-7-ethyl-2-(methoxymethyl)pynolo[l,2-b]pyridazin-3-yl]propanoic acid 1H NMR (CDCl3) 8 1.37 (1H, t, J = 8 Hz), 2.39-2.48 (2H, m), 2.83-2.94 (2H, m), 3.03 (2H, q, J = 8 Hz), 3.45 (1H, s), 4.65 (2H, s), 5.95 (1H, d, J = 5 Hz), 6.60 (1H, d, J = 5 Hz), 7.24 (1H, m), 7.35 (1H, br s), 7.40-7.46 (2H, m). MS(ESl+):m/z373(M + H). Example 493 4-[4-(3-chlorophenyl)-7-elhyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]bulanoic acid 1H NMR (CDC13) 6 1.37 (1H, t, J = 8 Hz), 1.64-1.78 (2H, m), 2.24 (2H, t, J = 8 Hz), 2.56-2.66 (2H, m), 3.04 (2H, q, J = 8 Hz), 3.45 (1H, s), 4.65 (2H, s), 5.94 (1H, d, J = 5 Hz), 6.59 (1H, d, J = 5 Hz), 7.21-7.29 (1H, overlapped with CDCl3), 7.36 (lH.br s), 7.39-7.46 (2H,m). MS (ESI+): m/z 387 (M + H). Example 494 5-{4-(5-bromo-3-pyridinyl)-7-ethyl-2-[(4-phenyl-l-piperazinyl)methyl]pyrrolo[l,2- b]pyridazin-3-yl}pentanoic acid 1H NMR (300 MHz, CDC13) 6 1.37 (1H, t, J = 7 Hz), 1.41-1.61 (4H, m), 2.22 (2H, t, J = 7 Hz), 2.49-2.67 (2H, m), 2.76 (4H, t, J = 5 Hz), 3.03 (2H, q, J = 7 Hz), 3.20 (4H, t, J = 5 Hz), 3.73 (2H, s), 5.89 (1H, d, J = 5 Hz), 6.58 (1H, d, J = 5 Hz), 6.85 (1H, dd, J = 8,8 Hz), 6.93 (2H, J = 8 Hz), 7.25 (2H, J = 8 Hz), 7.90 (1H, dd, J = 2, 2 Hz), 8.56 (1H, d, J = 2 Hz), 8.77 (1H, d, J = 2 Hz). Example 495 5-(4-(5-bromo-3-pyridinyl)-7-ethyl-2-{[(2-methoxyethyl)amino]melhyl}pyrrolo[l,2- b]pyridazin-3-yl)pentanoic acid 1H NMR (300 MHz, CDCl3) 6 1.28 (1H, t, J = 7 Hz), 1.32-1.43 (4H, m), 2.03-2.17 (2H, m), 2.23-2.41 (2H, m), 2.49-2.88 (2H, m), 2.98 (2H, q, J = 7 Hz), 3.37 (1H, s), 3.89-3.99 (2H, m), 4.51 (2H, s), 5.91 (1H, d, J = 5 Hz), 6.57 (1H, d, J = 5 Hz), 7.82 (1H, s), 8.47 (1H, s), 8.72 (1H, s). Example 496 5-[7-ethyl-2-(methoxymethyl)-4-(5-methoxy-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid mp 111-112°C 1H NMR (CDCl3) 6 1.37 (1H, t, J = 8 Hz), J .41-1.60 (4H, m), 2.21 (2H, br 1, J = 8 Hz), 2.30-2.70 (2H, m), 3.04 (2H, d, J = 8 Hz), 3.46 (1H, s), 3.90 (1H, s), 4.63 (2H, br d, J = 5 Hz), 5.92 (1H, d, J = 5 Hz), 6.58 (2H, d, J = 8 Hz), 7.25 (1H, m), 8.22 (1H, d, J = 1 Hz), 8.40 (1H, d, J = 3 Hz). MS (ESI+): m/z 398 (M + H). Example 497 5-[7-ethyl-4-(5-methoxy-3-pyridinyl)-2-methylpynolo[l,2-b]pyridazin-3-yl]pentanoic acid mp 133-134°C 1H NMR (CDCl3) 6 1.37 (1H, 1, J = 8 Hz), 1.40-1.62 (7H, m), 2.24 (2H, t, J = 8 Hz), 2.35-2.49 (2H, m), 2.56 (1H, s), 3.01 (2H, q, J = 8 Hz), 3.89 (1H, s), 5.87 (1H, d, J = 5 Hz), 6.51 (1H, d, J = 5 Hz), 7.23 (1H, m), 8.20 (1H, d, J = 1 Hz), 8.39 (1H, d,J = 1Hz). MS (ESI+): m/z 369 (M + H). Example 498 3-[7-ethyl-2-(methoxymethyl)-4-(5-methoxy-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]propanoic acid mp 164-165°C 1H NMR (CDCl3) 5 1.37 (1H, t, J = 8 Hz), 2.44-2.54 (2H, m), 2.80-3.00 (2H, m), 3.04 (2H, d, J = 8 Hz), 3.47 (1H, s), 3.89 (1H, s), 4.66 (2H, br s), 5.95 (1H, d, J = 5 Hz), 6.60 (1H, d, J = 5 Hz), 7.25 (1H, m), 8.22 (1H, d, J = 1 Hz), 8.38 (1H, d, J = 3 Hz). MS (ES1+): m/z 370 (M + H). Example 499 4-[7-ethyl-2-(methoxymethyl)-4-(5-methoxy-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]bulanoic acid mp 140-141°C 1H NMR (CDClj) 6 1.38 (1H, t, J = 8 Hz), 1.68-1.82 (2H, m), 2.25 (2H, t, J = 8 Hz), 2.52-2.75 (2H, m), 3.04 (2H, d, J = 8 Hz), 3.46 (1H, s), 3.92 (1H, s), 4.65 (2H, br d, J = 7 Hz), 5.94 OH, d, J = 5 Hz), 6.59 (1H, d, J = 5 Hz), 7.29 (1H, m), 8.23 (lH,d,J = l Hz),8.37(lH,d,J = 1Hz). MS (ESI+): m/z 384 (M + H). Example 500 5-[7-ethyl-2-(methoxymethyl)-4-(5-pyrimidinyl)pyrro]o[l,2-b]pyridazin-3-y]]pentanoic acid 1H NMR (CDC13) 5 1.38 (1H, t, J = 8 Hz), 1.40-1.64 (4H, m), 2.25 (2H, t, J = 8 Hz), 2.49-2.61 (2H, m), 3.04 (2H, d, J = 8 Hz), 3.47 (1H, s), 4.65 (2H, s), 5.91 (1H, d, J = 5 Hz), 6.62 (1H, d, J = 5 Hz), 8.82 (2H, s), 9.32 (1H, s). MS(ESI+):m/z369(M + H). Example 501 4-[4-(5-chloro-3-pyridinyl)-7-ethyl-2-(methoxymethy])pyrrolo[l,2-b]pyridazin-3-yl]butanoic acid mp 112-113˚0 1H NMR (CDCl3) 6 1.38 (1H, t, J = 8 Hz), 1.66-1.79 (2H, m), 2.28 (2H, t, J = 8 Hz), 2.52-2.71 (2H, m), 3.05 (2H, d, J = 8 Hz), 3.46 (1H, s), 4.66 (2H, br s), 5.92 (1H, d, J = 5 Hz), 6.61 (1H, d, J = 5 Hz), 7.77 (1H, m), 8.53 (1H, d, J = 1 Hz), 8.67 (lH,d,J = 2Hz). MS(ESl+):m/z388(M + H). Example 502 3-[4-(5-chloro-3-pyridinyl)-7-ethyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3-yljpropanoic acid mp 159-16CC 1H NMR (CDCl3) 5 1.38 (1H, t, J = 8 Hz), 2.47 (2H, br t, J = 8 Hz), 2.79-2.98 (2H, m), 3.04 (2H, d, J = 8 Hz), 3.47 (1H, s), 4.66 (2H, s), 5.93 (1H, d, J = 5 Hz), 6.67 (1H, d, J = 5 Hz), 7.74 (1H, m), 8.51 (1H, d, J = 1 Hz), 8.68 (1H, d, J = 3 Hz). MS (ESI+): m/z 374,376 (M + H). Example 503 5-[4-(5-chloro-3-pyridinyl)-7-ethyl-2-(methoxymelhyl)pyrrolo[l,2-b]pyridazin-3- yl]penlanoic acid mp 118-]19°C 1H NMR (CDCl3) 6 1.37 (1H, t, J = 8 Hz), 1.40-1.62 (7H, m), 2.24 (2H, t, J = 8 Hz), 2.45-2.64 (2H, in), 3.04 (2H, d, J = 8 Hz), 3.45 (1H, s), 4.63 (2H, s), 5.91 (1H, d, J = 5 Hz), 6.60 (1H, d, J = 5 Hz), 7.74 (1H, m),8.51 (lH,d, J = 1 Hz), 8.67 (1H, d,J = 2Hz). MS (ES1+): m/z 402,404 (M + H). Example 504 4-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(4H-l,2,4-triazol-4-ylmethyl)pyrrolo[l,2- b]pyridazin-3-yI]bulanoic acid 1H-NMR (CDC)3) 6 1.36 (1H, t, J = 7 Hz), 1.60 (2H, m), 2.32 (2H, m), 2.46 (2H, m), 3.01 (2H, q, J = 7 Hz), 5.75 (2H, m), 5.97 (1H, d, J = 5 Hz), 6.66 (1H, d, J = 5 Hz), 7.87 (1H, m), 7.97 (1H, s), 8.53 (1H, s), 8.65 (1H, s), 8.69 (1H, s). Example 505 4-{4-(5-bromo-3-pyridinyl)-2-[(cyclopropylamino)methyl]-7-ethylpyrrolo[l,2-b]pyridazin-3-yl}butanoic acid 1H-NMR (CDCl3) 6 0.56 (2H, m), 0.75 (2H, m), 1.38 (1H, t, J = 7 Hz), 1.65 (2H, m), 2.21 (2H, m), 2.50 (2H, m), 3.01 (2H,q, J = 7 Hz), 3.27 (1H, br), 4.29 (2H, s), 5.93 (1H, d, J = 5 Hz), 6.60 (1H, d, J = 5 Hz), 7.98 (1H, m), 8.55 (1H, m), 8.78 (lH,m). MS (ESf) m/z: 457 and 459 (M + H) Example 506 4-{4-(5-bromo-3-pyridinyl)-7-ethyl-2-[(2-oxo-l,3-oxazolidin-3-y])methyl]pyrrolo[l,2- b]pyridazin-3-y]}butanoic acid 1H-NMR (CDC13) 5 1.37 (1H, t, J = 7 Hz), 1.68 (2H, m), 2.31 (2H, m), 2.53 (2H, m), 2.98 (2H, q, J = 7 Hz), 3.77 (2H, m), 4.42 (2H, t,J = 7 Hz), 4.67 (2H, m), 5.94 (1H, d J = 5 Hz), 6.63 (1H, d, J = 5 Hz), 7.89(1H, m), 8.55 (1H, m), 8.78 (1H, m). Example 507 2-bromo-4-[3-(elhoxycarbonyI)-7-ethyl-2-me(hyIpyrrolo[l,2-b]pyridazin-4-yl]benzoic acid 1H-NMR (CDCl3) 6 1.00 (1H, t, J = 7 Hz), 1.38 (1H, t, J = 7 Hz), 2.62 (1H, s), 3.04 (2H, q, J = 7 Hz), 4.06 (2H, q, J = 7 Hz), 6.29 (1H, d, J = 5 Hz), 6.68 (1H, d, J = 5 Hz), 7.49 (2H, dd, J = 2 and 8 Hz), 7.82 (1H, d, J = 2 Hz), 8.07 (1H, d, J = 8 Hz). MS (ESI+) m/z: 431 and 433 (M + H) Example 508 5-[4-(3-cyanophenyl)-7-ethyl-2-(phenoxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid 1H-NMR (CDCl3) 6 1.25-1.49 (7H, m), 2.15 (2H, m), 2.54 (2H, m), 3.02 (2H, q, J = 7 Hz), 5.23 (2H, s), 5.86 (1H, d, J = 5 Hz), 6.60 (1H, d, J = 5 Hz), 6.98 (1H, 1, J = 8 Hz), 7.06 (2H, d, J = 8 Hz), 7.28 (2H, t, J = 8 Hz), 7.60 (2H, m), 7.67 (1H, s), 7.77 (lH,m). Example 509 5-[4-(3-cyanophenyl)-7-ethyl-2-(3-methyl-2-thienyl)pyrrolo[l,2-b]pyridazin-3- yl]pentanoic acid JH-NMR (CDCl3) 6 1.14-1.28 (4H, m), 1.37 (1H, t, J = 7 Hz), 2.01 (2H, t, J = 7 Hz), 2.23 (1H, s), 2.40 (2H, m), 3.02 (2H, q, J = 7 Hz), 5.92 (1J, d, J = 5 Hz)(, 6.64 (1H, d, J = 5 Hz), 6.94 (U, d, J = 5 Hz), 7.33 (1H, d, J = 5 Hz), 7.57-7.66 (2H, m), 7.73-7.76 (2H,m). Example 510 (2E)-4-[4-(3-cyanophenyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]-2-butenoic acid1H-NMR (CDCl3) 6 1.38 (1H, t, J = 7 Hz), 2.55 (1H, s), 3.03 (2H, q, J = 7 Hz), 3.09 (2H, d, J = 7 Hz), 5.45 (1H, dt, J = 7 and 16 Hz), 6.05 (1H, d, J = 5 Hz), 6.25 (1H, d, J = 16 Hz), 6.57 (1H, d, J = 5 Hz), 7.55 (1H, t, J = 8 Hz), 7.66+-7.72 (1H, m). MS (ES1+): m/z 345 (M+H) Example 511 4-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(methoxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]butanoic acid 1H NMR (CDCl3) 5 1 -37 (1H, t, J= 7 Hz), 1.68-1.84 (2H, m), 2.28 (2H, t, J= 7 Hz), 2.56-2.74 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.46 (1H, s), 4.66 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.92 (1H, m), 8.57 (1H, d, J= 2 Hz), 8.78 (1H, d, J=2Hz). MS (ESI'): m/z 430 432, MS (ESI+): m/z 432 434. The following compound(s) was(were) obtained in a similar manner to that of Example 159. Example 512 ethyl 4-[4-(2-chloro-4-pyridinyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]butanoale 1H NMR (CDC13) 6 1.26 (1H,t, J= 7 Hz), 1.36 (1H, t, J= 7 Hz), 1.35-1.45 (2H,m), 1.88 (2H, t, J= 7 Hz), 2.43-2.55 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 5.98 (1H, d, J= 4 Hz), 6.65 (1H, d, J= 4 Hz), 7.33 (1H, d, J= 5 Hz), 7.42-7.55 (6H,m),8.55QH,d,J=z). MS(ESI+):m/z448. Example 513 ethyl 3-[4-(2-chloio-4-pyridinyl)-7-ethyl-2-phenyIpyrrolo[l,2-b]pyridazin-3- yl]propanoate 1H NMR (CDCl3) 6 1.09 (1H, t, J= 7 Hz), 1.36 (1H, t, J= 7 Hz), 1.98-2.08 (2H, m), 2.75-2.85 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.92 (2H, q, J= 7 Hz), 6.00 (1H, d, J= 4 Hz), 6.67 (1H, d, J= 4 Hz), 7.32 (1H, d, J= 5 Hz), 7.42 (1H, s), 7.43-7.57 (, m), 8.55(lH,d,J=z). MS (ESI+): m/z 434. Example 514 methyl {2-[4-(2-chloro-4-pyridinyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3- yl]ethoxy} acetate 1H NMR (CDCl3) 5 1.36 (1H, t, J= 7 Hz), 2.73-2.85 (2H, t, J= 7 Hz), 3.03 (2H, t, J= 7 Hz), 3.15 (2H, t, J= 7 Hz), 3.74 (2H, s), 4.09 (1H, s), 6.02 (1H, d, J= 4 Hz), 6.67 (1H, d, J= 4 Hz), 7.39 (1H, m), 7.42-7.60 (6H, m), 8.53 (1H, d, J= 5 Hz). MS (ESI+): m/z 450. Example 515 ethyl 5-[4-(3-cyanophenyl)-7-elhy]-2-(3-methyl-2-thieriyl)py]'rolo[l52-b]pyiidazin-3- yl]propanoate 1H-NMR (CDCl3) 5 1.09-1.26 (7H, m), 1.36 (1H, t, J = 7 Hz), 1.93 (2H, t, J = 7 Hz), 2.23 (1H, s), 2.39 (2H, m), 3.03 (2H, q, J = 7 Hz), 4.03 (2H, q, J = 7 Hz), 5.93 (1H, d, J = 5 Hz), 6.64 (1H, d, J = 7 Hz), 6.96 (1H, d, J = 5 Hz), 7.33 (1H, d, J = 5 Hz), 7.60-7.67 (2H, m), 7.72-7.79 (2H, m). Example 5J6 methyl 5-[4-(3-cyanophenyl)-7-ethyl-2-(2-lhienyl)pyrrolo[l,2-b]pyridazin-3- yl]propanoate 1H-NMR (CDCl3) 5 1.21-1.47 (7H, m), 2.04 (2H, t, J = 7 Hz), 2.60 (2H, m), 3.05 (2H, q, J = 7 Hz), 3.61 (1H, s), 5.37 (1H, d, J = 5 Hz), 6.63 (1H, d, J = 5 Hz), 7.13 (1H, m), 7.36 (1H, m), 7.44 (1H, m), 7.62-7.78 (4H, m). Example 517 ethyl 3-[4-(3-cyanophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]propanoate 1H-NMR (CDCl3) 6 1.08 (1H, t, J = 7 Hz), 1.37 (1H, t, J = 7 Hz), 1.98 (2H, m), 2.75 (2H, m), 3.02 (2H, q, J = 7 Hz), 3.89 (2H, q, J = 7 Hz), 5.93 (1H, d, J = 5 Hz), 6.63 (1H, d, J = 5 Hz), 7.41-7.55 (, m), 7.57-7.78 (4H, m). MS(ESI+):m/z424(M + H) Example 518 ethyl 5-[4-(3-chlorophenyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate 1H-NMR (CDCl3) 6 1.02-1.25 (7H, m), 1.37 (1H, t, J = 7 Hz), 1.88 (2H, t, J = 7 Hz), 2.43 (2H, m), 3.01 (2H, q, J = 7 Hz), 4.00 (2H, q, J = 7 Hz), 5.96 (1H, d, J = 5 Hz), 6.60 (1H, d, J = 5 Hz), 7.29 (1H, m), 7.37-7.54 (8H, m). MS (ESI+): m/z 461 Example 519 4-(5-bromo-3-pyridinyl)-7-ethyl-2-phenylpyrrolo[l,2-b]pyridazine-3-carbonitrile 1H NMR (CDC13) 5 1.42 (1H, t, J = 8 Hz), 3.12 (2H, t, J = 8 Hz), 6.65 (1H, d, J = 5 Hz), 6.94 (1H, d, J = 5 Hz), 7.51-7.59 (1H, m), 7.83-7.91 (2H, m), 8.19 (1H, m), 8.85-8.92 (2H,m). MS (ESf): m/z 403,405 (M + H). The following compound(s) was(were) obtained in a similar manner to that of Example 175. Example 520 5-{4-(3-cyanophenyl)-7-ethyl-2-[(4-pyridinylmethoxy)metliyl]pyrrolo[l,2-b]pyridazin-3-yljpentanoicacid 1H NMR (CDCb) 6 1.38 (1H, t, J= 7 Hz), 1.36-1.57 (4H, m), 2.16 (2H, t, J= 7 Hz), 2.51-2.62 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.69 (2H, s), 4.78 (2H, s), 5.87 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.35 (2H, d, J= 5 Hz), 7.61 (2H, d, J= 5 Hz), 7.67 (1H, s), 7.77 (1H, m), 8.54 (2H, d, J= 5 Hz). MS (ESI˚): m/z 467, MS (ES1+): m/z 469. Example 521 5-{4-[3-(aminocarbonyl)phenyl]-7-ethyl-2-[(4-pyridinylmethoxy)methyl]pyrrolo[l,2-b]pyridazin-3-yl}pentanoic acid 1H NMR (CDC13) 6 1.38 (1H, t, J= 7 Hz), 1.47-1.68 (4H, m), 2.15-2.40 (2H, m), 2.40-2.56 (1H, m), 2.82-2.96 (1H, m), 3.05 (2H, q, J= 7 Hz), 4.68 (2H, s), 4.72 (1H, d, J= 17 Hz), 4.93 (1H, d,J= 17 Hz), 5.83 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.31 (2H, d, J= 5 Hz), 7.39 (1H, br), 7.45 (1H, d, J= 8 Hz), 7.58 (1H, t, J= 8 Hz), 7.69 (1H, br), 7.77 (1H, br), 7.98 (1H, d, J= 8 Hz), 8.57 (2H, d, J= 5 Hz). MS (ESF): m/z 485, MS (ES1+): m/z 487. Example 522 5-{4-(3-cyanophenyl)-7-ethyl-2-[(2-pyrazinylmethoxy)methyl]pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid 1H NMR (CDC13) 0 1 -38 (1H, t, J= 7 Hz), 1.30-1.57 (4H, m), 2.18 (2H, m), 2.48-2.65 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.83 (2H, s), 4.85 (2H, s), 5.86 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.61 (2H, d, J= 5 Hz), 7.68 (1H, s), 7.77 (1H, m), 8.53 (2H, d,J=z),8.76(lH,s). MS (ESF): m/z 468, MS (ESI+): m/z 470. Example 523 5-{4-(3-cyanophenyl)-7-elhyl-2-[(3-pyricliny]methoxy)methy]]pynolo[l,2-b]pyridazin-3-yl]pentanoic acid 1H NMR (CDCl3) 6 1.38 (1H, 1, J= 7 Hz), 1.38-1.57 (4H, m), 2.15 (2H, t, J= 7 Hz), 2.49-2.62 (2H, m), 3.04 (2H, q, J= 7 Hz), 4.69 (2H, s), 4.76 (2H, s), 5.85 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.33 (1H, m), 7.62 (2H, m), 7.67 (1H, s), 7.73-7.82 (2H, m), 8.53 (1H, d, J= 5 Hz), 8.67 (1H, s). MS (ESI-): m/z 467, MS (ESI+): m/z 469. Example 524 5-[4-(3-cyanopheny])-7-ethyl-2-(5-methyI-3-isoxazolyI)pyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid 1H-NMR (CDCl3) 6 1.34-1.52 (7H, m), 2.17 (2H, t, J = 7 Hz), 2.53 (1H, s), 2.77 (2H, m), 3.03 (2H, q, J = 7 Hz), 5.89 (1H, d, J = 5 Hz), 6.54 (1H, s), 6.67 (1H, d, J = 5 Hz), 7.63 (2H, m), 7.68 (1H, s), 7.78 (1H, m). Example 525 5-[4-(3-cyanophenyl)-7-ethy]-2-(2-thienyl)pyrrolo[ 1,2-b]pyridazin-3-yl]penlanoic acid 1H-NMR (CDCl3) 5 1.23-1.42 (7H, m), 2.07 (2H, t, J = 7 Hz), 2.58 (2H, m), 3.03 (2H, q, J = 7 Hz), 5.87 (1H, d, J = 5 hz), 6.56 (1H, d, J = 5 Hz), 7.13 (1H, m), 7.36 (1H, m), 7.43 (1H, d, J = 5 Hz), 7.62 (2H, m), 7.70 (1H, s), 7.76 (1H, m). Example 526 3-[4-(3-cyanophenyl)-7-ethyl-2-pheny]pyno]o[l,2-b]pyridazin-3-yl]propanoic acid 1H-NMR (CDCl3) 6 1.36 (1H, t, J = 7 Hz), 1.99 (2H, m), 2.75 (2H, m), 3.00 (2H, q, J = 7 Hz), 5.93 (1H, d, J = 5 Hz), 6.63 (1H, d, J = 5 Hz), 7.42-7.55 (, m), 7.57- 7.78 (4H,m). Example 527 5-[4-(3-chlorophenyl)-7-elhyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid 1H-NMR (CDCl3) S 1 -03-1.25 (4H, m), 1.36 (1H, t, J = 7 Hz), 1.90 (2H, t, J = 7 Hz), 2.41 (2H, m), 3.00 (2H, q, J = 7 Hz), 5.97 (1H, d, J = 5 Hz), 6.59 (1H, d, J = 5 Hz), 7.28 (1H, m), 7.35-7.54 (8H, m). MS(ESl+):m/z433(M+H) The following compound(s) was(were) obtained in a similar manner to thai of Example 180. Example 528 ethyl 5-[4-(3-cyanophenyl)-7-ethyl-2-(5-methyl-3-isoxazoIyI)pyrrolo[],2-b]pyridazin-3-yl]propanoate 1H-NMR (CDCl3) 5 1.22 (1H, t, J = 7 Hz), 1.32-1.46 (, m), 1.72 (2H, m), 2.10 (2H, 1, J = 7 Hz), 2.54 (1H, s), 2.78 (2H, m), 3.03 (2H, q, J = 7 Hz), 4.06 (2H, q, J = 7 Hz), 5.89 (1H, d, J = 5 Hz), 6.54 (1H, s), 6.66 (1H, d, J = 5 Hz), 7.62 (2H, m), 7.67 (lH,s), 7.77 (lH,m). The following compound(s) was(were) obtained in a similar manner to that of Preparation 176. Example 529 ethyl 4-[4-(aminocarbonyl)-3-bromophenyl]-7-ethyl-2-methylpyrrolo[l,2-b]pyridazine-3-carboxylate 1H-NMR (CDCl3) 6 1.03 (1H, t, J = 7 Hz), 1.37 (1H, t, J = 7 Hz), 2.60 (1H, s), 3.03 (2H, q, J = 7 Hz), 4.07 (2H, q, J = 7 Hz), 5.83 (1H, s, br), 6.19 (1H, s, br), 6.28 (1H, d, J = 5 Hz), 6.67 (1H, d, J = 5 Hz), 7.46 (1H, d, J = 8 Hz), 7.72 (1H, s), 7.77 (lH,d,J = 8Hz). The following compound(s) was(were) obtained in a similar manner to that of Example 184. Example 530 3-[2-(cyclopentylamino)-7-ethyl-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazin-4-yl]benzonitrile 1H-NMR (CDCb) 6 1.36 (1H, t, J = 7 Hz), 1.51-1.80 (6H, m), 2.15 (2H, m), 2.96 (2H, q, J = 7 Hz), 3.05 (1H, s), 4.27 (1H, m), 5.94 (1H, d, J = 5 Hz), 6.47-6.53 (2H, m), 7.53-7.59 (1H, m), 7.74 (1H, m). Example 531 3-[7-ethyl-2-(methylamino)-3-(methylsulfonyl)pyrrolo[l,2-b]pyridazin-4-yl]benzonitrile 1H-NMR (CDCl3) 6 1.37 (1H, t, J = 7 Hz), 2.94-3.07 (8H, m), 5.95 (1H, d, J = 5 Hz), 6.50 (2H, m), 7.54-7.59 (1H, m), 7.74 (J H, m). The following compound(s) was(were) obtained in a similar manner lo that of Example 225. Example 532 (2R,3R,4S,5S,6R)-2-({3-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(methoxymelhyl)pyrrolo[l,2-b]pyridazin-3-yl]propanoyl}amino)-6-{[(2,2-dimethylpropanoyl)oxy]methyl}tetrydro-2H-pyran-3,4,5-triyl tris(2,2-dimethylpropanoate) 1H-NMR (CDC13) 5 1.07 (9H, s), 1.11 (9H, s), 1.16 (9H, s), 1.18 (9H, s), 1.37 (1H, t, J = 7 Hz), 2.23 (2H, m), 2.84 (2H, m), 3.03 (2H, q, J = 7 Hz), 3.48 (1H, s), 3.91-4.21 (1H, m), 4.62-4.67 (2H, m), 5.00-5.26 (1H, m), 5.43 (2H, m), 5.91 (1H, d, J = 5 Hz), 6.55 (1H, m, br), 6.62 (1H, d, J = 5 Hz), 7.84 (1H, m), 8.51 (1H, m), 8.77 (lH,m). The following compound(s) was(were) obtained in a similar manner to that of Example 226. Example 533 [4-(3-chlorophenyl)-7-ethyl-2-(2-furyl)pyrrolo[l,2-b]pyridazin-3-yl]methanol 1H-NMR (CDCl3) 5 1.40 (1H, t, J = 7 Hz), 2.53 (1H, t, J = 7 Hz), 3.07 (2H, q, J = 7 Hz), 4.48 (2H, m), 6.23 (1H, d, J = 5 Hz), 6.62 (1H, m), 6.71 (1H, d, J = 5 Hz), 7.10 (1H, d, J = 5 Hz), 7.46-7.52 (1H, m), 7.61 (1H, m), 7.64 (1H, m). Example 534 [4-(2-chloro-4-pyridinyl)-7-ethyl-2-methylpyrrolo[l,2-b]pyridazin-3-yl]methanol 1H NMR (CDCl3) 5 1.38 (1H, t, J = 8 Hz), 3.05 (2H, q, J = 8 Hz), 3.45-3.55 (4H, m), 4.40 (2H, br d, J = 7 Hz), 4.77 (2H, br s), 6.22 (1H, d, J = 5 Hz), 6.70 (1H, d, J = 5 Hz), 8.11 (1H, m), 8.74 (1H, br s), 8.80 (1H, d, J = 2 Hz). MS(ESI+):m/z302(M + H). The following compound(s) was(were) obtained in a similar manner to that of Example 227. Example 535 (2R,3S,4S,5R,6R)-2-[(acetyloxy)melhyl]-6-({5-[4-(3-cyanophenyl)-7-elhyl-2-phenylpynolo[l,2-b]pyridazin-3-yl]pentyl}oxy)tetrydro-2H-pyran-3,4,5-triyl triacetate1H-NMR (CDCl3) 6 0.82-1 .18 (6H, m), 1.37 (1H, t, J = 7 Hz), 1.92-2.17 (14H, m), 2.35 (2H, m), 3.01 (2H, q, J = 7 Hz), 3.16 (1H, m), 3.62 (1H, m), 3.85 (1H, m), 4.11 (2H, m), 4.10 (2H, m), 4.30 (1H, d, J = 8.1 Hz), 4.96 (1H, m), 5.11 (1H, m), 5.35 (1H, m), 5.90 (1H, d, J = 5 Hz), 6.62 (1H, d, J = 5 Hz), 7.44-7.53 (, m), 7.60-7.80 (4H,m). The following compound(s) was(were) obtained in a similar manner to that of Example 228. Example 536 ethyl 3-[7-ethyl-2-(hydroxymethyl)-4-(5-melhyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]propanoate 1H NMR (CDCl3) 6 1.19 (1H, t, J= 7 Hz), 1.39 (1H, t, J= 7 Hz), 2.33 (2H, t, J= 7 Hz), 2.43 (1H, s), 2.70-2.82 (2H, m), 3.04 (2H, q, J= 7 Hz), 3.71 (1H, t, J= 5 Hz), 4.05 (2H, q, J= 7 Hz), 4.89 (2H, d, J= 5 Hz), 5.98 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.52 (1H, s), 8.42 (1H, d, J= 2 Hz), 8.56 (1H, d, J= 2 Hz). MS(ESl+):m/z368. Example 537 ethyl 4-[7-ethyl-2-(hydroxymethyl)-4-(5-methyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3- yl]butanoate 1H NMR (CDCb) 6 1.24 (1H, t, J= 7 Hz), 1.39 (1H, t, J= 7 Hz), 1.62-1.78 (2H, m), 2.16-2.28 (2H, m), 2.36-2.53 (2H, m), 2.44 (1H, s), 3.06 (2H, q, J= 7 Hz), 3.86 (1H, t, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 4.90 (2H, m), 5.96 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 7.53 (1H, s), 8.44 (1H, s), 8.56 (1H, s). MS (ES1+): m/z 382. Example 538 ethyl 5-[4-(3-cyanophenyl)-7-ethyl-2-(hydroxymethyl)pyrrolo[l,2-b]pyridazin-3- yl]pentanoate 1H NMR (CDCl3) 6 1.26 (1H, t, J= 7 Hz), 1.39 (1H, t, J= 7 Hz), 1.46-1.65 (4H, m), 2.16 (2H, t, J= 7 Hz), 2.32-2.44 (2H, m), 3.04 (2H, q, J= 7 Hz), 4.12 (2H, q, J= 7 Hz), 4.86 (2H, s), 5.91 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 758-7.68 (1H, m), 7.75-7.82 (lH,m). MS(ESI+):m/z406. Example 539 ethyl 4-[4-(5-bromo-3-pyridinyl)-7-elhyl-2-(hydroxymelhyl)pyrrolo[l,2-b]pyridazin-3- yljbulanoate 1H NMR (CDC13) 6 1.25 (1H, t, J= 7 Hz), 1.38 (1H, t, J= 7 Hz), 1.64-1.79 (2H, m), 2.23 (2H, t, J= 7 Hz), 2.42-2.53 (2H, m), 3.04 (2H, q, J= 7 Hz), 4.10 (2H, q, J= 7 Hz), 4.91 (2H, s), 5.97 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.89 (1H, m), 8.56 (1H, d, J= 2 Hz), 8.80 (1H, d, J= 2 Hz). MS(ESI+):m/z446 448. Example 540 ethyl 3-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(hydroxymethyl)pyrrolo[l,2-b]pyridazin-3- yl]propanoate 1H NMR (CDCl3) 6 1.20 (1H, t, J= 7 Hz), 1.38 (1H, t, J= 7 Hz), 2.32 (2H, m), 2.68-2.90 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.10 (2H, m), 4.89 (2H, s), 6.03 (1H, m), 6.65 (1H, m), 7.90 (1H, m), 8.58 (1H, m), 8.83 (1H, m). MS(ESI+):m/z432 434. Example 541 ethyl 4-[4-(5-chloro-3-pyridinyl)-7-ethyl-2-(hydroxymethyl)pyrrolo[l,2-b]pyridazin-3- yl]butanoate 1H NMR (300 MHz, CDCl3) 5 1.22 (1H, t, J = 7 Hz), 1.38 (1H, t, J = 7 Hz), 1.67 (2H, tt, J = 7, 7 Hz), 2.20 (2H, t, J = 7 Hz), 2.37-2.79 (2H, m), 3.04 (2H, q, J = 7 Hz), 3.77 (1H, t, J = 4 Hz), 4.07 (2H, q, J = 7 Hz), 4.91 (2H, d, J = 4 Hz), 5.96 (1H, d, J = 4 Hz), 6.61 (1H, d, J = 4 Hz), 7.73 (1H, dd, J = 2, 2 Hz), 8.52 (1H, d, J = 2 Hz),8.70(lH,d,J = 2Hz). Example 542 ethyl 3-[4-(3-chlorophenyl)-7-ethyl-2-(hydroxymethyl)pynolo[l,2-b]pyridazin-3- yl]propanoate 1H NMR (300 MHz, CDCl3) 6 1.20 (1H, 1, J = 7 Hz), 1.38 (1H, t, J = 7 Hz), 2.31 (2H, t, J = 8 Hz), 2.85 (2H, I, J = 8 Hz), 3.04 (2H, q, J = 7 Hz), 3.69-3.75 (1H, br s), 4.06 (2H, q, J = 7 Hz), 4.88 (2H, s), 6.00 (1H, d,J =4 Hz), 6.59 (1H, d, J = 4 Hz), 7.23-7.26 (1H, m), 7.36 (1H, s), 7.44-7.46 (2H, m). Example 543 ethyl 4-[4-(3-chlorophenyl)-7-ethyl-2-(hydroxymelhyl)pyrrolo[l,2-b]pyridazin-3- yl]butanoate 1H NMR (CDCb) 5 1.21 (1H, t, J = 8 Hz), 1.38 (1H, t, J = 8 Hz), 1.57 (1H, s), 1.59-1.74 (2H, m), 2.20 (2H, t, J = 8 Hz), 2.37-2.47 (2H, m), 3.03 (2H, q, J = 8 Hz), 3.84 (1H, t, J = 5 Hz), 4.06 (2H, q, J = 8 Hz),4.39 (2H, d, J = 5 Hz), 5.32 (2H, s), 5.96 (1H, d, J = 5 Hz), 6.56 (1H, d, J = 5 Hz), 7.21-7.29 (1H, overlappled with CDCl3), 7.36 (1H, br s), 7.39-7.47 (2H, m). Example 544 9-(5-bromo-3-pyridinyl)-6-ethyl-lH,1H-furo[3,4-e]pyrrolo[l,2-b]pyridazin-l-one 1H NMR (CDCl3) 6 1.42 (1H, t, J = 8 Hz), 3.11 (2H, q, J = 8 Hz), 5.32 (2H, s), 6.87 (1H, d, i = 5 Hz), 6.99 (1H, d, J = 5 Hz), 8.20 (1H, m), 8.83-8.87 (2H, m). MS (ESI+): m/z 358, 360 (M + H). 4-(5-bromo-3-pyridinyl)-7-ethyl-2-(hydroxymethy])pyrrolo[l,2-b]pyridazine-3-carboxylic acid 1H NMR (CDC13-CD30D) 6 1.40 (1H, t, J = 8 Hz), 3.09 (2H, q, J = 8 Hz), 4.93 (2H, s), 6.34 (1H, d,J = 5 Hz), 6.79 (1H, d, J = 5 Hz), 7.96 (1H, m), 8.55 (1H, br s), 8.73(lH,brs). MS (ESI+): m/z 376,378 (M + H). Example 545 3-[4-(5-bromo-3-pyridinyl)-7-ethyl-2-(melhoxymethyl)pyrrolo[l,2-b]pyridazin-3-yl]-N-[(2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrydro-2H-pyran-2-yljpropanamide 1H-NMR (DMSO-d6) 6 1.30 (1H, t ,J = 7 Hz), 2.21 (1H, m), 2.96 (2H, q, J = 7 Hz), 3.25-3.45 (8H, m), 3.66 (1H, m), 4.40 (1H, m), 4.55-4.67 (, m), 4.75 (1H, m), 5.85(lH,d,J = z),6.66(1H,d,J=z),8.23(lH,m),8.33(lH,d,br,J = 7 Hz), 8.61 (1H, m), 8.84 (1H, m). Example 546 3-[7-e1Hy]-2-phenyl-3-(5-{[(2R,3R,4S1HR,6R)-3,41H-trihydroxy-6- (hydroxynie1Hyl)tetiydro-2H-pyran-2-yl]oxy}pentyl)pyrrolo[J,2-b]pyridazin-4- y]]benzonitrile 1H-NMR (CDC13) 6 0.85-1.38 (6H, m), 1.46 (1H, t, J = 7 Hz), 2.13 (2H, m), 2.38 (2H, m), 2.65 (1H, m), 2.73 (1H, m), 3.02 (2H, q, J = 7 Hz), 3.23 (1H, m), 3.48-3.70 (4H, m), 3.80-4.01 (1H, m), 4.13 (1H, m), 5.90 (1H, d, J = 5 Hz), 663 (1H, d, J = 5 Hz), 7.42-7.55 (, m), 7.60-7.79 (4H, m). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 235. Example 547 N-(2-aminoe1Hyl)-3-[4-(5-bromo-3-pyridinyl)-7-elhyl-2-(me1Hoxymelhyl)pyrrolo[l,2-b]pyridazin-3-yl]propanamide 1H-NMR (CDC13) 6 1.37 (1H, t, J = 7 Hz), 2.29 (2H, m), 2.72-3.07 (6H, m), 3.33 (2H, q, J = 7 Hz), 3.49 (1H, s), 4.68 (2H, s), 5.93 (1H, d, J = 5 Hz), 6.06 (1H, m, br), 6.62 (1H, d, J = 5 Hz), 7.89 (1H, m), 8.55 (1H, m), 8.77 (1H, m). MS (ESf) m/z: 460 and 462 (M + H) 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 268. Example 548 e1Hyl 3-{7-e1Hyl-4-(5-me1Hyl-3-pyridinyl)-2-[(4-pyridinylme1Hoxy)me1Hyl]pyrrolo[l,2-b]pyridazin-3-yl}propanoate 1H NMR (CDCl3) 5 1.15 (1H, t, J= 7 Hz), 1.38 (1H, t, J= 7 Hz), 2.37 (2H, t, J= 7 Hz), 2.43 (1H, s), 2.86-3.01 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.99 (2H, q, J= 7 Hz), 4.68 (2H, s), 4.81 (2H, s), 5.95 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.27 (2H, d, J= 7 Hz), 7.51 (1H, s), 8.43 (1H, s), 8.56 (1H, s), 8.57 (2H, d, J= 7 Hz). MS (ES1+): m/z 459. Example 549 e1Hyl 3-{7-e1Hyl-4-(5-me1Hyl-3-pyriclinyl)-2-[(2-pyrazinylme1Hoxy)me1Hyl]pyrrolo[l,2- b]pyridazin-3-yl}propanoate 1H NMR (CDC1.0 6 1.16 (1H, t, J= 7 Hz), 1.38 (1H, t, J= 7 Hz), 2.39 (2H, t, J= 7 Hz), 2.43 (1H, s), 2.88-3.03 (2H, m), 3.04 (2H, q, J= 7 Hz), 4.01 (2H, q, J= 7 Hz), 4.83 (2H, s), 4.90 (2H, s), 5.94 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.53 (1H, s), 8.42 (1H, m), 8.48-8.55 (1H, m), 8.76 (1H, s). MS (ESI+): m/z 460. Example 550 e1Hyl 3-{7-e1Hyl-4-(5-me1Hyl-3-pyridinyl)-2-[(2-pyridinylme1Hoxy)me1Hyl]pyrrolo[l,2- b]pyridazin-3-yl}propanoate 1H NMR (CDCl3) 6 1.15 (1H, t, J= 7 Hz), 1.38 (1H, t, J= 7 Hz), 2.40 (2H, t, J= 7 Hz), 2.42 (1H, s), 2.88-3.00 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.99 (2H, q, J= 7 Hz), 4.79 (2H, s), 4.86 (2H, s), 5.92 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 7.16-7.23 (1H, m), 7.45-7.53 (2H, m), 7.68 (1H, m), 8.42 (1H, m), 8.53 (2H, m). MS (ES1+): m/z 459. Example 551 e1Hyl 4-{7-e1Hyl-4-(5-me1Hyl-3-pyridinyl)-2-[(4-pyridinylme1Hoxy)me1Hyl]pyrrolo[l,2- b]pyridazin-3-yl}butanoate 1H NMR (CDCl3) 6 1.18 (1H, t, J= 7 Hz), 1.38 (1H, t, J= 7 Hz), 1.60-1.80 (2H, m), 2.13-2.25 (2H, m), 2.43 (1H, s), 2.53-2.76 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.03 (2H, q, J= 7 Hz), 4.68 (2H, s), 4.83 (2H, m), 5.92 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.27 (2H, d, J= 5 Hz), 7.53 (1H, s), 8.42 (1H, s), 8.53 (1H, s), 8.55 (2H, d,J=z). MS(ESI+):m/z473. Example 552 e1Hyl 5-{4-(3-cyanophenyl)-7-e1Hyl-2-[(4-pyridinylme1Hoxy)me1Hyl]pyrrolo[l,2- b]pyridazin-3-yl}pentanoate 1H NMR (CDCl3) 5 1.22 (1H, t, J= 7 Hz), 1.38 (1H, t, J= 7 Hz), 1.35-1.57 (4H, m), 2.11 (2H, t, J= 7 Hz), 2.53-2.65 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.03 (2H, q,J= 7 Hz), 4.67 (2H, s), 4.78 (2H, s), 5.87 (1H, d, J= 4 Hz), 6.61 (1H, ci, J= 4 Hz), 7.28 (2H, d, J= 5 Hz), 7.61 (2H, m), 7.66 (1H, s), 7.78 (1H, m), 8.58 (2H, d, J= 5 Hz). MS(ESI+):m/z497. Example 553 e1Hyl 5-{4-(3-cyanopheny])-7-e1Hyl-2-[(2-pyrazinylme1Hoxy)me1Hy]]pyrro]o[l,2-b]pyridazin-3-y]}pentanoate 1H NMR (CDC13) 5 1 -22 (1H, t, J= 7 Hz), 1.38 (1H, t, J= 7 Hz), 1.35-1.58 (4H, m), 2.11 (2H, 1, J= 7 Hz), 2.55-2.65 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.10 (2H, q, J= 7 Hz), 4.82 (2H, s), 4.86 (2H, s), 5.86 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 7.62 (2H, m), 7.67 (1H, s), 7.78 (1H, m), 8.51 (2H, m), 8.74 (1H, s). MS(ESl+):m/z498. Example 554 e1Hyl 5-{4-(3-cyanophenyl)-7-e1Hyl-2-[(3-pyridinylme1Hoxy)me1HyI]pyrrolo[l,2- b]pyridazin-3-yl}pentanoate 1H NMR (CDCl3) 6 1.22 (1H, t, J= 7 Hz), 1.39 (1H, t, J= 7 Hz), 1.32-1.66 (4H, m), 2.10 (2H, t, J= 7 Hz), 2.48-2.60 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.08 (2H, q, J= 7 Hz), 4.66 (2H, s), 4.75 (2H, s), 5.86 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.28 (1H, m), 7.58-7.63 (2H, m), 7.66 (1H, s), 7.66-7.80 (2H, m), 8.54 (1H, m), 8.62 (lH,m). MS(ESI+):m/z497. Example 555 e1Hyl 5-{4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-[(4-pyridinylme1Hoxy)me1Hyl]pyrrolo[l,2- b]pyridazin-3-yl}pentanoate 1H NMR (CDCl3) 5 1.23 (1H, t, J= 7 Hz), 1.38 (1H, t, J= 7 Hz), 1.40-1.62 (4H, m), 2.16 (2H, t, J= 7 Hz), 2.53-2.71 (2H, m), 3.05 (2H, q, J= 7 Hz), 4.09 (2H, q, J= 7 Hz), 4.67 (2H, s), 4.78 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.31 (2H, d, J= 5 Hz), 7.88 (1H, m), 8.56 (1H, d, J= 2 Hz), 8.58 (2H, d, J= 5 Hz), 8.79 (lH,d,J=2Hz). Example 556 e1Hyl 5-{4-(5-bromo-3-pyridinyl)-7-elhyl-2-[(3-pyridinylme1Hoxy)me1Hyl]pyrrolo[l,2- b]pyridazin-3-yl}pentanoate 1H NMR (CDCl3) 6 1 -23 (1H, t, J= 7 Hz), 1.40 (1H, 1, J= 7 Hz), 1.30-1.60 (4H, m), 2.15 (2H, t, J= 7 Hz), 2.50-2.68 (2H, m), 3.06 (2H, q, J= 7 Hz), 4.12 (2H, q, .1= 7 Hz), 4.68 (2H, s), 4.78 (2H, s), 5.95 (1H, m), 6.63 (1H, m), 7.24-7.38 (1H, m), 7.75 (1H, m), 7.89 (1H, m), 8.58 (2H, s), 8.64 (1H, s), 8.80 (1H, s). MS(ESf):m/z551553. Example 557 e1Hyl 5-{4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-[(2-pyridinylme1Hoxy)me1Hyl]pyrrolo[l,2- b]pyridazin-3-yl}pentanoate 1H NMR (CDCl3) 6 1.24 (1H, t, J= 7 Hz), 1.37 (1H, t, J= 7 Hz), 1.40-1.58 (4H, m), 2.12 (2H, t, J= 7 Hz), 2.53-2.68 (2H, m), 3.03 (2H, q, J= 7 Hz), 4.10 (2H, q, J= 7 Hz), 4.78 (2H, s), 4.84 (2H, s), 5.92 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.22 (1H, m), 7.48 (1H, d, J= 8 Hz), 7.68-7.75 (1H, m), 7.88 (1H, m), 8.57 (2H, m), 8.78(lH,d,J=2Hz). Example 558 e1Hyl 5-{4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-[(2-pyrazinylme1Hoxy)me1Hyl]pyrrolo[l,2- b]pyridazin-3-yl}pentanoate 1H NMR (CDCb) 6 1.22 (1H, t, J= 7 Hz), 1.38 (1H, t, J= 7 Hz), 1.40-1.62 (4H, m), 2.15 (2H, t, J= 7 Hz), 2.53-2.72 (2H, m), 3.05 (2H, q, J= 7 Hz), 4.08 (2H, q, J= 7 Hz), 4.82 (2H, s), 4.86 (2H, s), 5.94 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.88 (1H, m), 8.52 (2H, m), 8.55 (1H, d, J= 2 Hz), 8.74 (1H, m), 8.79 (1H, d, J= 2 Hz). MS (ES1+): m/z 552 554. Example 559 e1Hyl 4-{4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-[(4-pyridinylme1Hoxy)me1Hyl]pynolo[l,2- b]pyridazin-3-yl}butanoate 1H NMR (CDCl3) 5 1.19 (1H, t, J= 7 Hz), 1.38 (1H, t, J= 7 Hz), 1.60-1.80 (2H, m), 2.22 (2H, t, J= 7 Hz), 2.55-2.74 (2H, m), 3.05 (2H, q, J= 7 Hz), 4.06 (2H, q, J= 7 Hz), 4.69 (2H, s), 4.83 (2H, s), 5.96 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.30 (2H, d, J= 6 Hz), 7.88 (1H, m), 8.56 (2H, d, J= 6 Hz), 8.57 (1H, m), 8.80 (1H, m). MS (ES1+): m/z 537 539. Example 560 e1Hyl 4-{4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-[(3-pyridinylmelhoxy)me1Hyl]pyrrolo[ 1,2- b]pyridazin-3-yl}butanoate 1H NMR (CDC13) 6 1.26 (1H, t, J= 7 Hz), 1.38 (1H, t, J= 7 Hz), 1.55-1.82 (2H, m), 2.18 (2H, t, J= 7 Hz), 2.52-2.72 (2H, m), 3.05 (2H, q, J= 7 Hz), 4.05 (2H, q, J= 7 Hz), 4.68 (2H, s), 4.83 (2H, s), 5.94 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.28 (1H, m), 7.73 (1H, d, J= 8 Hz), 7.88 (1H, m), 8.54 (2H, m), 8.62 (1H, s), 8.79 (1H, s) Example 561 e1Hyl 4-{4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-[(2-pyridinylme1Hoxy)me1Hyl]pyrrolo[l,2- b]pyridazin-3-yl}butanoate 1H NMR (CDC13) 6 1.26 (1H, t, J= 7 Hz), 1.38 (1H, t, J= 7 Hz), 1.63-1.82 (2H, m), 2.18 (2H, t, J= 7 Hz), 2.55-2.75 (2H, m), 3.06 (2H, q, J= 7 Hz), 4.00 (2H, q, J= 7 Hz), 4.80 (2H, s), 4.88 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.22 (1H, m), 7.48 (1H, d, J= 8 Hz), 7.71 (1H, t, J= 8 Hz), 7.89 (1H, m), 8.55 (2H, m), 8.78(lH,d,J=2Hz). MS(ESI+):m/z537 539. Example 562 e1Hyl 4-{4-(5-bromo-3-pyridinyl)-2-[(cyclopropylme1Hoxy)me1Hyl]-7-e1Hylpyrrolo[l,2- b]pyridazin-3-yl}butanoate 1H NMR (CDCl3) 6 0.25 (2H, m),0.60 (2H, m), 1.08-1.22 (1H, m), 1.22 (1H, t, J= 7 Hz), 1.37 (1H, t, J= 7 Hz), 1.69-1.82 (2H, m), 2.21 (2H, t, J= 7 Hz), 2.56-2.72 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.42 (2H, d, J= 7 Hz), 4.04 (2H, q, J= 7 Hz), 4.73 (2H, s), 5.91 (1H, d, J= 4 Hz), 6.59 (1H, d, J= 4 Hz), 7.89 (1H, m), 8.56 (1H, d, J=2Hz),8.79(lH,d,J=2Hz). MS (ESf): m/z 500 502. Example 563 e1Hyl 4-{4-(5-biomo-3-pyridiny])-7-e1Hyl-2-[(2-pyrazinylme1Hoxy)mc1Hyl]pyrrolo[l,2- b]pyridazin-3-yl}butanoate 1H NMR (CDCl3) 6 1-19 (1H, t, J= 7 Hz), 1.38 (1H, t, J= 7 Hz), 1.70-1.82 (2H, m), 2.23 (2H, t, J= 7 Hz), 2.56-2.76 (2H, m), 3.06 (2H, q, J= 7 Hz), 4.04 (2H, q, J= 7 Hz), 4.84 (2H, s), 4.95 (2H, m), 5.94 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.89 (1H, m), 8.50 (2H, m), 8.56 (1H, s), 8.74 (1H, s), 8.79 (1H, m). MS (ESI+): m/z 538 540. Example 564 e1Hyl 3-{4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-[(4-pyridinylme1Hoxy)me1Hyl]pyrrolo[l,2- b]pyridazin-3-yl}propanoate 1H NMR (CDC13) & 1.16 (1H, t, J= 7 Hz), 1.38 (1H, t, J= 7 Hz), 2.41 (2H, t, J= 7 Hz), 2.85-3.07 (2H, m), 3.06 (2H, q, J= 7 Hz), 4.02 (2H, q, J= 7 Hz), 4.68 (2H, s), 4.81 (2H, s), 5.95 (1H, d, J= 4 Hz), 6.65 (1H, d, J= 4 Hz), 7.31 (2H, d, J= 6 Hz), 7.87 (1H, m), 8.55 (1H, m), 8.56 (2H, d, J= 6 Hz), 8.79 (1H, d, J= 2 Hz). MS(ESI+):m/z523 525. Example 565 e1Hyl 4-(4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-{ [2-(tetrydro-2H-pyran-2- yloxy)e1Hoxy]me1Hyl}pyrrolo[l,2-b]pyridazin-3-yl)butanoate 1H NMR (CDCl3) 5 1.20 (1H, t, J= 7 Hz), 1.37 (1H, t, J= 7 Hz), 1.46-1.93 (8H, m), 2.21 (2H, t, J= 7 Hz), 2.55-2.76 (2H, m), 3.02 (2H, q, J= 7 Hz), 3.46-3.56 (1H, m), 3.60-3.68 (1H, m), 3.74-3.82 (2H, m), 3.83-3.96 (2H, m), 4.03 (2H, q, J= 7 Hz), 4.63 (1H, m), 4.77 (2H, s), 5.91 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 7.89 (1H, m), 8.56 (1H, d, J= 2 Hz), 8.78 (1H, d, J= 2 Hz). Example 566 e1Hyl 4-{4-(5-chloro-3-pyridinyl)-7-e1Hyl-2-[(4-pyridinylme1Hoxy)me1Hyl]pyrrolo[l,2- b]pyridazin-3-yl}butanoate 1H NMR (300 MHz, CDCl3) 6 1.19 (1H, t, J = 7 Hz), 1.38 (1H, t, J = 7 Hz), 1.70 (2H, t, J = 7 Hz), 2.19 (2H, t, J = 7 Hz), 2.55-2.67 (2H, m), 3.04 (2H, q, J = 7 Hz), 4.03 (2H, q, J = 7 Hz), 4.69 (2H, s), 4.83 (2H, s), 5.94 (1H, d, J = 5 Hz), 6.63 (1H, d, J = 5 Hz), 7.29 (2H, d, J = 6 Hz), 7.73 (1H, dd, J = 2, 2 Hz), 8.52 (1H, d, J = 2 Hz), 8.58 (2H, d, J = 6 Hz), 8.69 (1H, d, J = 2 Hz). Example 567 e1Hyl 3-[4-(3-chlorophenyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrrolo[ 1,2-b]pyridazin-3- yl]propanoate 1H NMR (CDCl-0 5 1.20 (1H, t, J = 8 Hz), 1.37 (1H, t, J = 8 Hz), 2.33-2.44 (2H, m), 2.84-2.94 (2H, m), 3.03 (2H, q, J = 8 Hz), 3.45 (1H, s), 4.05 (2H, q, J = 8 Hz), 4.64 (2H, s), 5.94 (1H, d, J = 5 Hz), 6.58 (1H, d, J = 5 Hz), 7.21-7.29 (1H, overlappled wi1H CDC13), 7.36 (1H, br s), 7.38-7.46 (2H,m). Example 568 e1Hyl 4-[4-(3-chlorophenyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrrolo[l,2-b]pyridazin-3- yl]butanoate 1H NMR (CDCl3) 5 1.20 (1H, t, J = 8 Hz), 1.37 (1H, t, J = 8 Hz), 1.62-1.78 (2H, m), 2.14-2.28 (2H, m), 2.53-2.66 (2H, m), 3.04 (2H, q, J = 8 Hz), 3.46 (1H, s), 4.04 ˚ (2H, q, J = 8 Hz), 4.65 (2H, s), 5.93 (1H, d, J = 5 Hz), 6.58 (1H, d, J = 5 Hz), 721-7.29 (1H, overlappled wi1H CDC13), 7.36 (IH, br s), 7.39-7.46 (2H, rn). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 272. Example 569 e1Hyl 5-{4-(5-bromo-3-pyridinyl)-2-[(l,l-dioxido-4-1Hiomorpholinyl)me1Hyl]-7- e1Hylpyrrolo[l,2-b]pyridazin-3-yl}pentanoate 1H NMR (300 MHz, CDC13) 5 1.23 (1H, t, J = 7 Hz), 1.36 (1H, t, J = 7 Hz), 1.39-1.53 (4H, m), 2.19 (2H, t, J = 7 Hz), 2.50-2.61 (2H, m), 3.00 (2H, q, J = 7 Hz), 3.10 (4H, t, J = 6 Hz), 3.21 (4H, t, J = 6 Hz), 3.85 (2H, s), 4.10 (2H, q, J = 7 Hz), 5.92 (IH, d, J = 4 Hz), 6.61 (IH, d, J = 4 Hz), 7.88 (IH, dd, J = 2,2 Hz), 8.55 (IH, d,J = 2Hz),8.80(lH,d,J=2Hz). Example 570 e1Hyl 5-[4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-(4-1Hiomorpholinylme1Hyl)pyrrolo[l,2- b]pyridazin-3-yl]pentanoate 1H NMR (300 MHz, CDC13) 8 1.23 (1H, t, J = 7 Hz), .1.37 (1H, t, J = 7 Hz), 1.41- 1.54 (4H, m), 2.19 (2H, t, J = 7 Hz), 2.50-2.61 (2H, m), 2.66 (4H, t, J = 4 Hz), 2.85 (4H, t, J = 4 Hz), 3.01 (2H, q, J = 7 Hz), 3.67 (2H, s), 4.10 (2H, q, J = 7 H), 5.88 (1H, d, J = 5 Hz), 6.57 (1H, d, J = 5 Hz), 7.88 (1H, dd, J = 2, 2 Hz), 8.55 (1H, d, J = 2 Hz), 8.79 (1H, d, J = 2 Hz). Example 571 e1Hyl 5-(4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-{[4-(2-hydroxye1Hyl)-l- piperazinyl]me1Hyl}pyrrolo[l,2-b]pyridazin-3-yl)pentanoa1e 1H NMR (300 MHz, CDC13) 6 1.23 (1H, t, J = 7 Hz), 1.36 (1H, t, J = 7 Hz), 1.40- 1.55 (4H, m), 2.18 (2H, t, J = 7 Hz), 2.48-2.66 (12H, in), 3.02 (2H, q, J = 7 Hz), 3.61 (2H, t, J = 5 Hz), 3.66 (2H, s), 4.10 (2H, q, J = 7 Hz), 5.88 (1H, d, J = 4 Hz), 6.57 (1H, d, J = 4 Hz), 7.88 (1H, dd, J = 2,2 Hz), 8.55 (1H, d, J = 2 Hz), 8.78 (1H, d,J = 2Hz). Example 572 e1Hyl 4-[4-(5-chloro-3-pyridinyl)-7-e1Hyl-2-(4-1Hiomorpholinylme1Hyl)pyirolo[l,2- b]pyridazin-3-yl]butanoate NMR (300 MHz, CDCl3) 6 1.21 (1H, t, J = 7 Hz), 1.37 (1H, t, J = 7 Hz), 1.70 (2H, tt, J = 7, 7 Hz), 2.19 (2H, t, J = 7 Hz), 2.50-2.67 (6H, m), 2.86 (4H, t, J = 5 Hz), 3.02 (2H, q, J = 7 Hz), 3.70 (2H, s), 4.05 (2H, q, J = 5 Hz), 5.89 (1H, d, J = 4 Hz), 6.58 (1H, d, J = 4 Hz), 7.74 (1H, dd, J = 2,2 Hz), 8.52 (1H, d, J = 2 Hz), 8.68 (1H, d,J = 2Hz). Example 573 e1Hyl 4-[4-(5-chloro-3-pyridinyl)-7-e1Hyl-2-(4-moipholinylme1Hyl)pyrrolo[l,2- b]pyridazin-3-yl]butanoate 1H NMR (300 MHz, CDCl3) 8 1.21 (1H, t, J = 7 Hz), 1.37 (1H, t, J = 7 Hz), 1.72 (2H, tt, J = 7,7 Hz), 2.20 (2H, t, J = 7 Hz), 2.56-2.69 (6H, m), 3.02 (2H, q, J = 7 Hz), 3.68-3.71 (6H, m), 4.05 (2H, q, J = 7 Hz) 5.89 (1H, d, J = 4 Hz), 6.58 (1H, d, J = 4 Hz), 7.74 (1H, dd, J = 2, 2 Hz), 8.53 (1H, d, J = 2 Hz), 8.69 (1H, d, J = 2 Hz). Example 574 e1Hyl 3-[4-(5-brono-3-pyridinyl)-7-e1Hyl-2-(4-moipho]iny]me1Hyl)pyiTolo[l,2-b]pyridazin-3-y]]propanoale 1H NMR (300 MHz, CDC1-0 5 1.21 (1H, t, J = 7 Hz), 1.34 (1H, t, J = 7 Hz), 2.47-2.54 (2H, m), 2.59 (4H, l, J = 5 Hz), 2.81-2.95 (2H, m), 3.02 (2H, q, J = 7 Hz), 3.67 (4H, t, J = 5 Hz), 3.69 (2H, s), 4.07 (2H, q, J = 7 Hz), 5.90 (IH, d, J = 4 Hz), 6.59 (1H, d, J = 4 Hz), 7.88 (1H, dd, J = 2,2 Hz), 8.55 (1H, d, J = 2 Hz), 8.79 (1H, d, J = 2 Hz). Example 575 e1Hyl 4-[4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-(4-morpholinylme1Hyl)pyrrolo[l,2- b]pyridazin-3-yl]butanoate 1H NMR (300 MHz, CDC13) 6 1.21 (1H, t, J = 7 Hz), 1.36 (1H, t, J = 7 Hz), 1.73 (2H, tt, J = 7,7 Hz), 2.20 (2H, t, J = 7 Hz), 255-2.69 (6H, m), 3.02 (2H, q, J = 7 Hz), 3.69 (4H, t, J = 5 Hz), 4.05 (2H, q, J = 7 Hz), 5.89 (1H, d, J = 4 Hz), 6.58 (1H, d, J = 4 Hz), 7.89 (1H, dd, J = 2,2 Hz), 8.57 (1H, d, J = 2 Hz), 8.79 (1H, d, J = 2 Hz). Example 576 e1Hyl 4-{4-(5-chloro-3-pyridinyl)-2-[(cyclopropylamirio)me1Hyl]-7-e1Hylpyrrolo[l,2- b]pyridazin-3-yl}butanoate 1H NMR (300 MHz, CDC13) 6 0.46-0.52 (4H, m), 1.21 (1H, t, J = 7 Hz), 1.38 (1H, t, J = 7 Hz), 1.71 (2H, tt, J = 8,8 Hz), 2.21 (2H, t, J = 8 Hz), 2.32-2.39 (1H, m), 2.45-2.54 (2H, m), 3.04 (2H, q, J = 7 Hz), 4.06 (2H, q, J = 7 Hz), 4.07 (2H, s), 5.89 (1H, d, J = 4 Hz), 6.57 (1H, d, J = 4 Hz), 7.72 (1H, dd, J = 2,2 Hz), 8.50 (1H, d,J = 2Hz),8.68(lH,d,J=2Hz). Example 577 e1Hyl 5-(4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-{[(2- phenoxye1Hyl)amino]me1Hyl}pyrrolo[l,2-b]pyridazin-3-yl)pentanoate 1H NMR (300 MHz, CDC13) 6 1.23 (1H, t, J = 7 Hz), 1.37 (1H, t, J = 7 Hz), 1.40-1.56 (4H, m), 2.18 (2H, t, J = 8 Hz), 2.41-2.52 (2H, m), 3.04 (2H, q, J = 7 Hz), 3.19 (2H, t, J = 5 Hz), 4.07 (2H, s), 4.09 (2H, q, J = 7 Hz), 4.17 (2H, t, J = 5 Hz), 5.90 (1H, d, J = 4 Hz), 6.57 (1H, d, J = 4 Hz), 6.92-6.98 (1H, m), 7.29-7.32 (2H, m), 7.86 (1H, dd, J = 2,2 Hz), 8.54 (1H, d, J = 2 Hz), 8.78 (1H, d, J = 2 Hz). Example 578 e1Hyl 5-(4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-{[(2- hydroxyetliyl)(me1Hyl)amino]me1Hyl}pyrrolo[l,2-b]pyridazin-3-yl)pentanoale 1H NMR (300 MHz, CDC13) b 1.23 (1H, t, J = 7 Hz), 1.37 (1H, t, J = 7 Hz), 1.42-1.63 (4H, m), 2.20 (2H, t J = 8 Hz), 2.38 (1H, s), 2.53-2.64 (2H, m), 2.75 (2H, I, J = 5 Hz), 3.02 (2H, q, J = 7 Hz), 3.66 (2H, t, J = 5 Hz), 3.77 (2H, s), 4.10 (2H, q, J = 7 Hz), 5.90 (1H, d, J = 4 Hz), 6.59 (1H, d, J = 4 Hz), 7.88 (1H, dd, J = 2,2 Hz), 8.55 (1H, d, J = 2 Hz), 8.78 (1H, d, J = 2 Hz). Example 579 e1Hyl 5-[4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-(l-piperidinylme1Hyl)pyrrolo[l,2-b]pyridazin- 3-yl]pentanoate 1H NMR (300 MHz, CDCl3) 8 1.23 (1H, t, J = 7 Hz), 1.36 (1H, t, J = 7 Hz), 1.42-1.58 (6H, m), 1.69 (4H, tt, J = 5,5 Hz), 2.18 (2H, t, J = 8 Hz), 2.53-2.64 (2H, m), 3.02 (2H, q, J = 7 Hz), 3.19 (4H, t, J = 5 Hz), 3.60 (2H, s), 4.07 (2H, q, J = 7 Hz), 5.86 (1H, d, J = 5 Hz), 6.54 (1H, d, J = 5 Hz), 7.89 (1H, dd, J = 2,2 Hz), 8.56 (1H, d, J = 2Hz),8.75(lH,d,J = 2Hz). Example 580 e1Hyl 3-[4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-(4-1Hiomorpholinylme1Hyl)pyrrolo[l,2- b]pyridazin-3-yl]propanoate 1H NMR (300 MHz, CDCl3) 6 1.23 (1H, t, J = 7 Hz), 1.37 (1H, t, J = 7 Hz), 2.46 (2H, t, J = 8 Hz), 2.64 (4H, t, J = 5 Hz), 2.86 (6H, m), 3.02 (2H, q, J = 7 Hz), 3.69 (2H, s), 4.06 (2H, q, J = 7 Hz), 5.91 (1H, d, J = 5 Hz), 6.60 (1H, d, J = 5 Hz), 7.88 (1H, dd, J = 2, 2 Hz), 8.56 (1H, d, J = 2 Hz), 8.80 (1H, d, J = 2 Hz). Example 581 e1Hyl 3-(4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-{ [4-(2-hydroxye1Hyl)-l - piperazinyl]me1Hyl}pyrrolo[l,2-b]pyridazin-3-yl)propanoate 1H NMR (300 MHz, CDCl3) 6 1.21 (1H, t, J = 7 Hz), 1.37 (1H, t, J = 7 Hz), 2.46-2.63 (12H, m), 2.80-2.94 (2H, m), 3.03 (2H, q, J = 7 Hz), 3.61 (2H, t, J = 5 Hz), 3.70 (2H, s), 4.08 (2H, q,J = 7 Hz), 5.90 (1H, d, J = 5 Hz), 6.59 (1H, d, J = 5 Hz), 7.88 (1H, dd, J = 2,2 Hz), 8.56 (1H, d, J = 2 Hz), 8.79 (1H, d, J = 2 Hz). Example 582 e1Hyl 5-[4-(5-biomo-3-pyridinyl)-7-e1Hyl-2-(l-pyrro]idinylme1Hyl)pyrrolo[l,2- ]pyridazin-3-yl]pentanoate 1H NMR (300 MHz, CDC13) 8 1 -23 (1H, t, J = 7 Hz), 1.37 (1H, t, J = 7 Hz), 1.40-1.55 (4H, m), 1.75-1.80 (4H, m), 2.19 (2H, t, J = 7 Hz), 2.54-2.66 (6H, m), 3.02 (2H, q, J = 7 Hz), 3.76-3.81 (2H,m), 4.10 (2H, q, J = 7 Hz), 5.87 (1H, d, J = 5 Hz), 6.55 (1H, d, J = 5 Hz), 7.89 (1H, dd, J = 2, 2 Hz), 8.56 (1H, d, J = 2 Hz), 8.77 (1H, d, J = 2 Hz). Example 583 e1Hyl 5-{4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-[(4-phenyl-l-piperazinyl)me1Hyl]pyrrolo[l,2- b]pyridazin-3-yl}pentanoate 1H NMR (300 MHz, CDC13) 6 1.21 (1H, t, J = 7 Hz), 1.38 (1H, t, J = 7 Hz), 1.41-1.54 (4H, m), 2.17 (2H, t, J = 7 Hz), 2.53-2.68 (2H, m), 2.75 (4H, t, J = 5 Hz), 3.03 (2H, q, J = 7 Hz), 3.19 (4H, t, J = 5 Hz), 3.73 (2H, s), 4.07 (2H, q, J = 7 Hz), 5.89 (1H, d, J = 5 Hz), 6.58 (1H, d, J = 5 Hz), 6.85 (1H, dd, J = 8, 8 Hz), 6.93 (2H, J = 8 Hz), 7.25 (2H, J = 8 Hz), 7.89 (1H, dd, J = 2,2 Hz), 8.56 (1H, d, J = 2 Hz), 8.78 (lH,d,J = 2Hz). Example 584 e1Hyl5-(4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-{[(2- me1Hoxye1Hyl)amino]me1Hyl}pyrrolo[l,2-b]pyridazin-3-yl)pentanoate }U NMR (300 MHz, CDCl3) 5 1.23 (1H, t, J = 7 Hz), 1.37 (1H, t, J = 7 Hz), 1.41-1.60 (4H, m), 2.19 (2H, t, J = 7 Hz), 2.43-2.52 (2H, m), 2.96 (2H, t, J = 5 Hz), 3.03 (2H, q, J = 7 Hz), 3.40 (1H, s), 3.58 (2H, t, J = 5 Hz), 3.99 (2H, s), 4.10 (2H, q, J = 7 Hz), 5.89 (1H, d, J = 5 Hz), 6.56 (1H, d, J = 5 Hz), 7.87 (1H, dd, J = 2,2 Hz), 8.54 (1H, d, J = 2 Hz), 8.78 (1H, d, J = 2 Hz). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 385. Example 585 3-[4-(5-bromo-3-pyridiny])-7-elhy]-2-(me1Hoxymelhyl)pyrroIo[l,2-b]pyridazin-3-yl]-N-[2-hydroxy-l,l-bis(hydroxymelhyl)e1Hyl]propanamide 1H-NMR (CDCl3) 6 137 (1H,t, J = 7 Hz), 2.25-3.10 (6H, m), 3.49 (1H, s), 3.58 (4H, m),3.81 (2H,m),455(2H,s),5.97(lH,d,J=z),61H4(IH,s),6.64(lH,d,J = 5 Hz), 7.93 (1H, m), 8.52 (1H, m), 8.78 (1H, m). Example 586 tert-butyl [2-({3-[4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrro]o[l,2- b]pyridazin-3-yl]propanoyl}amino)e1HyI]carbamate 1H-NMR (CDCl3) 6 1.37 (1H, t, J = 7 Hz), 1.43 (9H, s), 2.26 (2H, m), 2.88 (2H, m), 3.04 (2H, q, J = 7 Hz), 3.20 (2H, m), 3.28 (2H, m), 3.48 (1H, s), 4.67 (2H, s), 4.85 (1H, s, br), 5.93 (1H, d, J = 5 Hz), 6.20 (1H, s, br), 6.63 (1H, d, J = 5 Hz), 7.88 (1H, m), 8.53 (1H, m), 8.79 (1H, m). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 330. Example 587 e1Hyl 5-[2-{[2-(benzylamino)-2-oxoe1Hoxy]me1Hyl}-7-e1Hyl-4-(5-me1Hyl-3-pyridinyl)pyrrolo[ 1 ,2-b]pyridazin-3-yl]pentanoate 1H NMR (CDCl3) 6 1.22 (1H, t, J= 7 Hz), 1.34 (1H, t, J= 7 Hz), 1.33-1.55 (4H; m), 2.12 (2H, t, J= 7 Hz), 2.43 (1H, s), 2.40-2.56 (2H, m), 2.96 (2H, q, J= 7 Hz), 4.07 (2H, q, J= 7 Hz), 4.19 (2H, s), 4.52 (2H, d, J= 7 Hz), 4.76 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.59 (1H, d, J= 4 Hz), 7.06 (1H, br), 7.23-7.38 (, m), 7.49 (1H, s), 8.40 (1H,S),8.54(1H,S). MS (ESI+): m/z 543. 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 333. Example 588 e1Hyl4-[4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-(4H-l,2,4-triazol-4-ylme1Hyl)pyrro]o[l,2-b]pyridazin-3-yl]butanoate 1H-NMR (CDCl3) 8 1.22-1.34 (6H, m), 1.67 (2H, m), 2.23 (2H, m), 2.51 (2H, m), 2.98(2H,q,J = 7Hz),4.21 (2H, q, J = 7 Hz), 5.67 (2H, m), 5.97 (1H, d, J = 5 Hz), 6.63 (1H, d, J = 5 Hz), 7.85 (1H, m), 7.96 (1H, s), 8.34 (1H, s), 8.53 (1H, m), 8.79 (1H, m). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 336. Example 589 e1Hyl 5-(7-e1Hyl-4-(5-me1Hyl-3-pyridinyl)-2-{[(phenylsulfonyl)araino]me1Hyl}pyrrolo[l,2-b]pyridazin-3-yl)pentanoate 1H NMR (CDC13) 6 1.23 (1H, t, J= 7 Hz), 1.37 (1H, t, J= 7 Hz), 1.26-1.57 (4H, m), 2.16 (2H, t, J= 7 Hz), 2.33-2.46 (2H, m), 2.42 (1H, s), 2.98 (2H, q, J= 7 Hz), 4.11 (2H, q, J= 7 Hz), 4.38 (2H, m), 5.91 (1H, br), 5.92 (1H, d, J= 4 Hz), 6.58 (1H, d, J= 4 Hz), 7.43-7.55 (4H, m), 7.93 (2H, d, J= 8 Hz), 8.33 (1H, d, J= 2 Hz), 8.54 (lH,dsJ=2Hz). MS(ESI+):m/z 535. 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 340. Example 590 e1Hyl 4-{4-(5-bromo-3-pyridinyl)-2-[(cyclopropylamino)me1Hyl]-7-e1Hylpyrrolo[l,2-b]pyridazin-3-yl}butanoate 1H-NMR (CDCl3) 5 0.48 (4H, m), 1.19 (1H, t, J = 7 Hz), 1.37 (1H, t, J = 7 Hz), 1.70 (2H, t, J = 7 Hz), 2.22 (2H, m), 2.50 (2H, m), 2.95-3.07 (1H, m), 3.96-4.12 (4H, m), 5.90 (1H, d, J = 5 Hz), 6.57 (1H, d, J = 5 Hz), 7.88 (1H, m), 8.54 (1H, m), 8.77 (lH,m). Example 591 To a suspension of L1A1H4 (113 mg) in 1HF (10 mL) was added e1Hyl [4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-me1Hylpyrrolo[l,2-b]pyridazin-3-yl]acetate (600 mg) under ice-water cooling and 1He mixture was stirred at 0 °C for 2 hours. To 1He mixture was added potassium sodium tartrate solution and 1He insolubles were filterred off. After evaporation of solvent, 1He residue was partitioned between AcOEt and water. 1He organic layer was separated, washed wi1H brine, dried over MgSO4, and evaporated in vacuo. 1He residue was purified by silica gel column chromatography eluting wi1H a mixture of hexane and AcOEt (5:1 - 1:1) to give 2-[4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-mclhylpyrrolo['1 ,2-b]pyridazin-3-yl]e1Hanol as yellow oil (246 mg). 2-[4-(5-bromo-3'pyridinyl)-7-e1HyI-2-meihylpyrrolo[l,2-b]pyridazin-3-yl]e1Hanol 1H NMR (CDC13) 5 137 (1H, t, 3= 7 Hz), 2.60 (1H, s), 2.72-2.84 (2H, m), 3.03 (2H, q,J=7Hz),3.65(2H,t,J=7Hz),5.89(1H,d,J=4Hz),655(lH,d,J=4Hz), 7.91 (1H, t, J= 2 Hz), 8.56 (1H, d, J= 2 Hz), 8.76 (1H, d, J= 2 Hz). MS(ESI+):m/z360 362. Example 592 A mixture of 3-[4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-me1Hylpyrrolo[l,2-b]pyridazin-3-yl]propanoic acid (1.07 g), diphenylphosphoryl azide (1.14 g) and Et3N (0.576 mL) in BuOH (30 mL) was heated under reflux for 2 hours. After evaporation of solvent, 1He residue was partitioned between AcOEt and water. 1He organic layer was separated, washed wi1H aq NC03 solution and brine, dried over MgS04, and evaporated in vacuo. 1He residue was purified by silica gel column chromatography eluting wi1H a mixture of hexane and AcOEt (20:1 - 3:1) to give tert-butyl {2-[4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-me1Hylpyrrolo[l,2-b]pyridazin-3-yl]e1Hyl}carbamate as yellow oil (450 mg). tert-butyl {2-[4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-me1Hylpyrrolo[l,2-b]pyridazin-3- yl]e1Hyl} carbamate 1H NMR (CDCb) 6 1.37 (9H5 s), 1.37 (1H, t, J= 7 Hz), 2.64 (1H, s), 2.62-2.75 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.10-3.27 (2H, m), 4.40-4.52 (1H, m), 5.89 (1H, d, J= 4 Hz), 6.55 (1H, d, J= 4 Hz), 7.89 (1H, m), 8.53 (1H, m), 8.77 (1H, m). Example 593 To a suspension of 60% N (74 mg) in DMF (3 mL) was added e1Hyl 3-[4-(5-bromo-3-pyridinyl)-7-e1Hy]-2-(hydroxyme1Hyl)pyrrolo[l,2-b]pyridazin-3-yl]propanoate (200 mg) under ice-water cooling, and 1He mixture was stirred at 0 °C for 0.5 hour. To 1His was added 3-(bromomelbyl)pyridine hydrobromide (234 mg) under ice-water cooling, and 1He mixture was stirred at ambient temperature for 2 hours. 1He mixture was partitioned between AcOEt and water. 1He aqueous layer was separated, acidified to pH 3-4 wi1H HC1 and extracted wi1H AcOEt. 1He organic layer was washed wi1H water and brine, dried over MgS04, and evaporated in vacuo. 1He residue was purified by silica gel column chromatography eluting wi1H a mixture of CHCl3 and MeOH (100:1 - 20: J) to give 3-{4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-[(3~pyridinylme1Hoxy)me1Hyl]pyrrolo[l,2-b]pyridazin-3-yl}propanoic acid as a yellow powder (110 mg). 3-{4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-[(3-pyridinylme1Hoxy)me1Hyl]pyrrolo[l,2- b]pyridazin-3-yl}propanoic acid 1H NMR (CDCb) 5 1.39 (1H,1, J= 7 Hz), 2.41 (2H, t, J= 7 Hz), 2.80-2.98 (2H, m), 3.04 (2H, q, J= 7 Hz), 4.70 (2H, s), 4.83 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.63 (1H, d5 J= 4 Hz), 7.32-7.38 (1H, m), 7.81 (1H, d, J= 8 Hz), 7.87 (1H, m), 8.52 (1H, d, J= 8 Hz), 8.53 (1H, d, J= 2 Hz), 8.63 (1H, s), 8.77 (1H, d, J= 2 Hz). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 593. Example 594 4-{4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-[(2-me1Hoxye1Hoxy)me1Hyl]pyrrolo[l,2-b]pyridazin-3~yl}butanoic acid ]U NMR (CDCl3) 5 1.37 (1H, t, J= 7 Hz), 1.72-1.83 (2H, m), 2.28 (2H, t, J= 7 Hz), 2.60-2.77 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.39 (1H, s), 3.62 (2H, m), 3.77 (2H, m), 4.75 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.92 (1H, m), 8.56 (1H, d, J= 2 Hz), 8.77 (1H, d, J= 2 Hz). MS (ESI-): m/z 474 476, MS (ESf): m/z 476 478. Example 595 3-{4_(5-bromo-3-pyridinyl)-7-e1Hyl-2-[(2-pyridinylme1Hoxy)me1Hyl]pyrrolo[l,2-b]pyridazin-3-yl}propanoic acid 1H NMR (CDCb) 6 1.38 (1H, t, J= 7 Hz), 2.48-2.62 (2H, m), 2.98-3.10 (2H, m), 3.05 (2H, q, J= 7 Hz), 4.82 (2H, s), 4.88 (2H, s), 5.94 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.27 (1H, m), 7.48 (1H, d, J= 8 Hz), 7.77 (1H, t, J= 8 Hz), 7.90 (1H, m), 8.56 (2H,m), 8.80 (lH,m). MS(ESl+):m/z495 497. Example 596 3-{45-bromo-3-pyridiny])-2-[(cycIopropylme1Hoxy)melhyl]-7-e1Hy]pyrro]o[l,2-b]pyridazin-3-yl}propanoic acid 1HNMR(CDa3)6 0.25(2H,m),058(2H,m),1.12(lH,m), 1.37 (1H, t, J= 7 Hz), 2.40-2.63 (2H, m), 2.85-3.05 (2H, m), 3.02 (2H, q, J= 7 Hz), 342 (2H, d, J= 7 Hz), 4.73 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.89 (1H, m), 8.55 (1H, d, J= 2 Hz), 8.77 (1H, d, J= 2 Hz). MS (ESF): m/z 456 458, MS (ESI+): m/z 458 460. Example 597 3-{4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-[(2'pyrazinylmelhoxy)me1Hyl]pyrrolo[l,2-b]pyridazin-3~yl}propanoic acid 1H NMR (CDC13) 5 1.38 (1H, t, J= 7 Hz), 2.48 (2H, t, J= 7 Hz), 2.85-3.09 (2H, m), 3.06 (2H, q, J= 7 Hz), 4.84 (2H, s), 4.92 (2H, s), 5.96 (1H, d, J= 4 Hz), 6.65 (1H, d, J= 4 Hz), 7.90 (1H, m), 8.48-8.62 (1H, m), 8.77 (2H, m). Example 598 A mixture of e1Hyl 4-(4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-{[2-(tetrydro-2H-pyran-2-yloxy)e1Hoxy]me1Hyl}pyrro]o[l,2-b]pyridazin-3-yl)butanoate (89 mg) and pyridinium p-toluenesulfonate (0.8 mg) in MeOH (5 mL) was heated under reflux for 2 hours. After evaporation of solvent, 1He residue was purified by silica gel column chromatography eluting wi1H a mixture of hexane and AcOEt (10:1 - 1:1) to give e1Hyl 4-{4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-[(2-hydroxye1Hoxy)me1Hyl]pyrrolo[l,2-b]pyridazin-3-yl}butanoate as yellow oil (69 mg). e1Hyl 4-{4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-[(2-hydroxye1Hoxy)me1Hyl]pyrrolo[l,2-b]pyridazin-3-yl}butanoate 1HNMR(CDCl3)5l.22(1H,lJ=7Hz),1.37(1H,t,J=7Hz), 1.69-1.84 (2H,m), 2.22 (2H,1, J= 7 Hz), 2.53-2.72 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.76 (2H, m), 3.83 (2H, m), 4.07 (2H, q, J= 7 Hz), 4.79 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.89 (1H, m), 8.56 (1H, d, J= 2 Hz), 8.79 (1H, d, J= 2 Hz). MS(ESI+):ni/z490 492. Example 599 To a suspension of 60% N (69.5 mg) in DMF (3 mL) was added e1Hyl 5-[4-(5-bromo-3-pyridinyl)-7-e1HyI-2-(hydroxyme1Hyl)pyrrolo[J,2-b]pyridazin-3-yl]pentanoate (200 nig) under ice-water cooling and 1He mixture was stirred at 0 °C for 0.5 hour. To 1His was added 4-morpholinecarbonyl chloride (659 mg) and 1He mixture was stirred at ambient temperature for 15 hours. 1He mixture was partitioned between AcOEt and water. 1He organic layer was separated, washed wi1H water and brine, dried over MgSO1H, and evaporated in vacuo. 1He residue was purified by silica gel column chromatography eluting wi1H a mixture of hexane and AcOEt (20:1 -1:1) to give [4-(5-bromo-3-pyridinyl)-3-(5-e1Hoxy-5-oxopentyl)-7-e1Hylpyrrolo[l,2-b]pyridazin-2-yl]me1Hyl 4-morpholinecarboxylate as yellow oil (75 mg). [4-(5-bromo-3-pyridinyl)-3-(5-e1Hoxy-5-oxopentyl)-7-e1Hylpyrrolo[l,2-b]pyridazin-2-yljme1Hyl 4-morpholinecarboxylate 1H NMR(CDC13) 6 1.23 (1H, t, J= 7 Hz), 1.37 (1H,t, J= 7 Hz), 1.40-1.60 (4H,m), 2.18 (2H, t, J= 7 Hz), 2.42-2.54 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.53-3.57 (4H, m), 3.63-3.78(4H,m),4.09(2H,q,J=7Hz),5.33(2H,s),5.93(lH,d,J=4Hz),6.62 (1H, d, J= 4 Hz), 7.87 (1H, m), 8.54 (1H, d, J= 2 Hz), 8.78 (1H, d, J= 2 Hz). MS (ESI˚): m/z 573 575. 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 599. Example 600 e1Hyl 5-[4-(5-bromo-3-pyridinyl)-2-({[(dime1Hylamino)carbonyl]oxy}me1Hyl)˚-7-e1Hylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate 1H NMR (CDC13) 6 1.23 (1H, t, J= 7 Hz), 1.36 (1H, t, J= 7 Hz), 1.35-1.60 (4H, m), 2.17 (2H, t, J= 7 Hz), 2.44-2.57 (2H, m), 2.98 (6H, s), 3.03 (2H, q, J= 7 Hz), 4.09 (2H, q, J= 7 Hz), 5.30 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.87 (1H, m), 8.54 (1H, d, J= 2 Hz), 8.78 (1H, d, J= 2 Hz). MS(ESl+):m/z531533. Example 601 [4-(5-bromo-3-pyridiny])-3-(5-elhoxy-5-oxopentyl)-7-e1Hy]pyrrolo[J,2-b]pyridazin-2- yl]me1Hyl J -pyrrolidinecarboxylate 1H NMR (CDC1.0 6 1.23 (1H, t, J= 7 Hz), 1.36 (1H, t, J= 7 Hz), 1.38-1.60 (4H, m), J .86-1.98 (4H, m), 2.J7 (2H, t, J= 7 Hz), 2.44-2.57 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.36-3.52 (4H, m), 4.1 J (2H, q, J= 7 Hz), 5.32 (2H, s), 5.92 (1H, d, J= 4 Hz), 6.61 (1H, d, J= 4 Hz), 7.87 (1H, m), 8.55 (1H, d, J= 2 Hz), 8.78 (1H, d, J= 2 Hz). Example 602 elhyl 5-{4-(5-bromo-3-pyridinyl)-7-e1Hyl-2- [({[me1Hyl(phenyl)amino]carbonyl}oxy)me1Hyl]pyrrolo[l,2-b]pyridazin-3-yl}pentanoate1H NMR (CDCl3) 6 1.20 (1H, t, J= 7 Hz), 1.37 (1H, t, J= 7 Hz), 1.32-1.57 (4H, m), 2.13 (2H, t, J= 7 Hz), 2.33-2.48 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.38 (1H, s), 4.08 (2H, q, J= 7 Hz), 5.34 (2H, s), 5.92 (1H, d, J= 4 Hz), 6.60 (1H, d, J= 4 Hz), 7.20-7.38 (, m), 7.83 (1H, s), 8.49 (1H, s), 8.77 (1H, s). Example 603 [4-(5-bromo-3-pyridinyl)-3-(4-e1Hoxy-4-oxobutyl)-7-e1Hylpyrrolo[l,2-b]pyridazin-2-yl]me1Hyl 4-morpholinecarboxylate 1H NMR (CDC13) 6 1 -20 (1H, t, J= 7 Hz), 1.37 (1H, t, J= 7 Hz), 1.63-1.80 (2H, m), 2.22 (2H, t, J= 7 Hz), 2.44-2.65 (2H, m), 3.03 (2H, q, J= 7 Hz), 3.54 (4H, m), 3.68 (4H, m), 4.05 (2H, q, J= 7 Hz), 5.37 (2H, s), 5.94 (1H, d, J= 4 Hz), 6.62 (1H, d, J= 4 Hz), 7.87 (1H, m), 8.55 (1H, d, J= 2 Hz), 8.78 (1H, d, J= 2 Hz). MS(ESI+):m/z559 561. Example 604 e1Hyl 4-[4-(5-bromo-3-pyridinyl)-2-({[(dime1Hylamino)carbonyl]oxy}me1Hyl)-7- e1Hylpyrrolo[ 1,2-b]pyridazin-3-yl]butanoate 1H NMR (CDCl3) 6 1.20 (1H,t, J= 7 Hz), 1.36 (1H,t, J= 7 Hz), 1.66-1.79 (2H,m), 2.20 (2H, t, J= 7 Hz), 2.46-2.62 (2H, m), 2.97 (6H, s), 3.03 (2H, q, J= 7 Hz), 4.04 (2H, q, J= 7 Hz), 5.34 (2H, s), 5.93 (1H, d, J= 4 Hz), 6.63 (1H, d, J= 4 Hz), 7.89 (1H, m), 8.56 (1H, d, J= 2 Hz), 8.78 (1H, d, J= 2 Hz). MS(ESl+):m/z517 519. Example 605 e1Hyl 3-[4-(51Hromo-3-pyridiny])-2-({[(dime1Hy]amino)carbonyl]oxy}niclhyl)-7-e1Hylpyrrolo[3,2-b]pyridazin-3-yl]propanoate 1H NMR (CDCl3) 5 1.20 (1H, t, J= 7 Hz), 1.36 (1H, t, J= 7 Hz), 2.37 (2H, t, J= 7 Hz), 2.82-2.93 (2H, m), 2.97 (6H, s), 3.03 (2H, q, J= 7 Hz), 4.05 (2H, q, J= 7 Hz), 5.32 (2H,s),5.96(1H,d,J=4Hz),6.63(lH,d,J=4Hz),7.88(1H,m),854(lH,d, J=2Hz),8.78(lH,d,J=2Hz). Example 606 To a solution of sodium hydride (93.1 mg) in DMF (4 mL) was added e1Hyl 3-[4-(3-chlorophenyl)-7-e1Hyl-2-(hydroxyme1Hyl)pyrrolo[l,2-b]pyridazin-3-yl]propanoate (150 mg) under ice water cooling and 1He mixture was stirred at 1His temperature for 1 hour. To 1His was added 4-(bromome1Hyl)pyridine hydrobromide (196 mg) and 1He mixture was stirred for 1 hour at ambient temperature. 1He reaction was quenched by adding water. 1He mixture was extracted wi1H CHQ3. 1He organic layer was washed wi1H water and brine, dried over MgS04 and evaporated in vacuo. 1He residue was purified by silica gel column chromatography eluting wi1H a mixture of CHO3-MeOH = 30-1 to give 3-{4-(3-chlorophenyl)-7-e1Hyl-2-[(4-pyridinylme1Hoxy)me1Hyl]pyrrolo[l,2-b]pyridazin-3-yl}propanoic acid (18 mg) as a yellow solid. 3-{4-(3-chlorophenyl)-7-e1Hyl-2-[(4-pyridinylme1Hoxy)me1Hyl]pyrroIo[l,2-b]pyridazin-3-yl}propanoicacid 1H NMR (300 MHz, CDCfe) 5 1.39 (1H, t, J = 7 Hz), 2.33 (2H, t, J = 7 Hz), 2.84-2.91 (2H, m), 3.04 (2H, q, J = 7 Hz), 4.73 (2H, s), 4.82 (2H, s), 5.96 (1H, d, J = 5 Hz), 6.62 (1H, d, J = 5 Hz), 7.23-7.26 (1H, m), 7.36-7.38 (1H, m), 7.42-7.44 (2H, m), 8.41(2H,d,J = z). MS(m/z)450(M+H). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 606. Example 607 3_{4_(3_chlorophenyl)-7-e1Hyl-2-[(3-pyridinylme1Hoxy)me1Hyl]pyrrolo[l,2-b]pyridazin-3- yljpropanoic acid 1H NMR (300 MHz, CDC13) 5 1.39 (1H, t, J = 7 Hz), 2.32-2.38 (2H,m), 2.84-2.92 (2H, m), 3.04 (2H, q, J = 7 Hz), 4.70 (2H, s), 4.82 (2H, s), 5.94 (1H, d, J = 5 Hz), 6.60 (1H, d, J = 5 Hz), 7.2J-7.24 (1H, m), 7.31-7.36 (2H, m), 7.40-7.42 (2H, m), 7.80 (2H, d, J = 8 Hz), 8.51 (1H, d, J = 5 Hz), 8.64 (1H, s). Example 608 3-{4-(3-chloropheny])-7-e1Hy]-2-[(2-pyraziny]me1Hoxy)rne1Hyl]pyrrolo[l,2-b]pyridazin-3-yljpropanoic acid 1H NMR (300 MHz, CDCl3) 5 1.38 (1H, t, J = 7 Hz), 2.42 (2H, t, J = 7 Hz), 2.91-2.97 (2H, m), 3.03 (2H, q, J = 7 Hz), 4.83 (2H, s), 4.90 (2H, s), 5.96 (2H, d, J = 5 Hz), 6.62 (2H, d, J = 5 Hz), 7.23-7.26 (1H, m), 7.36 (1H, s), 7.43-7.44 (2H, m), 8.51-8.53 (2H,m), 8.75 (lH,s). Example 609 A solution of 5-[7-e1Hyl-2-me1Hyl-4-(2-vinyl-4-pyridinyl)pyrrolo[l ,2-b]pyridazin-3-yl]pentanoic acid (15 mg) in MeOH was added 10% Pd/C (2 rng). 1He mixture was stirred under under hydrogen atomosphere (1 atm) for 6 h. 1He reaction mixture was filtered 1Hrough Celite and 1He filtrate was concentrarted in vacuo. 1He residue was triturated wi1H hexane to give 5-[7-e1Hyl-4-(2-e1Hyl-4-pyridinyl)-2-me1Hylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid (14 mg) as an yellow solid. 5-[7-e1Hyl-4-(2-e1Hyl-4-pyridinyl)-2-me1Hylpyrrolo[l,2-b]pyridazin-3-yl]pentanoicacid 1H NMR (CDCl3) 5 1.29-1.64 (10H, m), 2.18-2.30 (2H, m), 2.45-2.48 (2H, m), 2.56 (1H, s), 2.91-3.06 (4H, m), 5.84 (1H, d, J = 5 Hz), 6.53 (1H, d, J = 16 Hz), 6.51 (1H, d, J = 5 Hz), 7.25-7.32 (2H, m), 8.69 (1H, br s). Example 610 To a solution of e1Hyl 4-[4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-(hydroxyme1Hyl)pyrrolo[l,2-b]pyridazin-3-yl]butanoate (70.0 mg) in toluene (1 mL) was added tributylphosphine (0.098 mL), l,3-oxazolidin-2-one (34.1 mg) in 1Hat order in an ice ba1H. After stirring for 5 minutes, to 1He mixture was added 1,1-(azodicarbonyl)dipiperidine (98.9 mg). 1He mixture was stirred for 10 minutes in 1He ba1H, and 8 hours at room temperature. Hexane (5 mL) was added, and 1He mixture was filtered. 1He filtrate was evaporated. Preparative 1Hin layer chromatography (e1Hyl acetale-hexane = 1-1) afforded e1Hyl 4-{4-(5-bromo-3-pyridinyl)-7-e1Hy]-2-[(2-oxo-'J,3-oxazoIidin-3-y])mc1Hy)]pyrro]o['l,2-b]pyridazin-3-yl}butanoate as an yellow gum (25.0 vng). e1Hyl 4-{4-(5-bromo-3-pyridiny])-7-e1Hyl-2-[(2-oxo-l,3-oxazoIidin-3- yl)me1HyI]pyrroIo[ 1,2-b]pyridazin-3-yl}butanoate 1H-NMR (CDC13) 6 1.20 (1H, t, J = 7 Hz), 1.369 (1H, t, J = 7 Hz), 1.65 (1H, t, J = 7 Hz), 2.25 (2H, t, J = 7 Hz), 2.51 (2H, m), 2.99 (2H, q, J = 7 Hz), 3.79 (2H, t, J = 7 Hz), 4.04 (2H, q, J = 7 Hz), 4.43 (2H, t, J = 7 Hz), 4.69 (2H, m), 5.95 (1H, d, J = 5 Hz), 6.61 (1H, d, J = 5 Hz), 7.87 (1H, m), 8.55 (1H, m), 8.80 (1H, m). Example 611 To a solution of 2-bromo-4-[3-(e1Hoxycarbonyl)-7-e1HyI-2-me1Hylpyrrolo[l,2-b]pyridazin-4-yl]benzoic acid (50.0 rng) in tetrydrofuran (1 mL) was added a solution of 1 M borane-tetrydrofuran complex (0.348 mL) in an ice ba1H. After stirring for 2 hours at room temperature, additional solution of 1He borane-tetrydrofuran complex (0.348 mL) was added. 1He mixture was stirred for 15 hours at room temperature. 1He mixture was parititioned between e1Hyl acetate and 1 N hydrochloric acid. 1He organic layer was washed wi1H water, saturated sodium bicarbonate, and brine, dried over magnesium sulfate, and evaporated to give e1Hyl 4-[3-bromo-4-(hydroxyme1HyJ)phenyl]-7-e1HyI-2-me1Hylpyrrolo[l,2-b]pyridazine-3-carboxylate as an yellow oil (54.2 mg). e1Hyl 4-[3-bromo-4-(hydroxyme1Hyl)phenyl]-7-e1Hyl-2-me1Hylpyrrolo[l,2-b]pyridazine-3- carboxylate 1H-NMR (CDCl3) 5 0.99 (1H, t, J = 7 Hz), 1.38 (1H, t, J = 7 Hz), 2.59 (1H, s), 3.03 (2H, q, J = 7 Hz), 4.07 (2H, q, J = 7 Hz),4.82 (2H, s), 6.33 (1H, d, J = 5 Hz), 6.66 (1H, d, J = 5 Hz), 7.44 (1H, d, J = 8 Hz), 7.58 (1H, d, J = 8 Hz), 7.67 (1H, s). Example 612 To a solution of 2-(2-{2-[7-e1Hyl-2-me1Hyl-4-(5-me1Hyl-3-pyridinyl)pyrrolo[l32-b]pyridazin-3-yl]e1Hoxy}e1Hoxy)e1Hyl acetate (62.0 mg) in me1Hanol (1 mL) was added potassium carbonate (22.2 mg). After stirring for 1.5 hour, 1He solvent was evaporated off. Preparative 1Hin layer chromatography (CHCh-MeOH = 20-1) affroded 1He desired product as an yellow gum (54.J mg). 1He gum was dissolved in 1 N HC1 (1 mL), and 1He solution was lyophilized to give a dark green gum, which was crystalyzed upon standing. 1He crystal was triturated in diisopropyl e1Her to give 2-(2-{2-[7-e1Hyl-2-me1Hyl-4-(5-me1Hyl-3-pyridinyl)pyrrolo[],2-b]pyridazin-3-yl]e1Hoxy}e1Hoxy)e1Hanol hydrochloride as an yellow powder (40.3 mg). 2-(2-{2-[7-e1Hyl-2-me1Hyl-4-(5-me1Hyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]e1Hoxy}e1Hoxy)e1Hanol hydrochloride 1H-NMR (DMSO-d6): 1.29 (1H, t, J = 7 Hz), 2.51 (1H, s), 2.56 (1H, s), 2.62 (2H, m), 2.94 (2H, q, J = 7 Hz), 3.30-3.47 (10H, m), 5.84 (1H, d, J = 5 Hz), 6.59 (1H, d, J = 5 Hz), 8.26 (1H, m), 8.77 (1H, m), 8..85 (1H, m). Example 613 A mixture of e1Hyl 5-[2-(bromome1Hyl)-4-(3-cyanophenyl)-7-e1Hylpyrrolo[l,2-b]pyridazin-3-yl]pentanoate (70.0 mg), phenol (21.1 mg), and pottassium carbonate (31.0 mg) in N,N-dime1Hylformamide was stirred for 2.5 hours at room temperature. 1He mixture was partitioned between e1Hyl acetate and 1 N hydrochloric acid. 1He organic layer was washed wi1H water, saturated sodium bicarbonate, and brine, dried over magnesium sulfate, and evaporated to give e1Hyl 5-[4-(3-cyanophenyl)-7-e1Hyl-2-(phenoxyme1Hyl)pyrrolo[l,2-b]pyridazin-3-yl]pentanoate as an yellow gum (77.5 mg, 108%). e1Hyl 5-[4-(3-cyanophenyl)-7-e1Hyl-2-(phenoxyme1Hyl)pyrrolo[l,2-b]pyridazin-3-yl]propanoate 1H-NMR (CDC13) 6 1.21 (1H, t, J = 7 Hz), 1.35-1.53 (7H, m), 2.07 (2H, m), 2.54 (2H, m), 3.03 (2H, q, J = 7 Hz), 4.05 (2H, q, J = 7 Hz), 5.24 (2H, s), 5.86 (1H, d, J = 5 Hz), 6.65 (1H, d, J = 5 Hz), 6.80-7.01 (1H, m), 7.03 (2H, d, J = 9 Hz), 7.32 (2H, t, J = 9 Hz), 7.55-7.63 (2H, m), 7.67 (1H, s), 7.76 (1H, m). MS(ESl+):m/z482(M + H) Example 614 A mixture of 4-(3-cyanophenyl)-7-e1Hyl-3-(me1Hylsulfonyl)pyrrolo[J,2- b]pyridazin-2-yl Irifluoromelhanesulfonate (50.0 mg), 3-furylboronic acid (23.6 nig), dichlorobis(triphenylphosphine)palladium (3.71 mg), and 2 N sodium carbonate (44.8 mg in 0.2 mL of water) in dioxane was stirred for 20 minutes at 85°C. 1He mixture was partitioned between EtOAc and water, and 1He organic layer was washed wi1H brine, dried, and evaporated. Preparative 1Hin layer chromatography (EtOAc-hexane = 1-1) afforded 3-[7-e1Hy]-2-(2-furyl)-3-(me1Hylsulfonyl)pyrrolo[l,2-b]pyridazin-4-yl]benzonitrile as an orange solid (11.5 mg). 3-[7-e1Hyl-2-(2-furyl)-3-(me1Hylsulfonyl)pyrrolo[l,2-b]pyridazin-4-yl]benzonitrile 1H-NMR (CDC13) 6 1.40 (1H, t, J = 7 Hz), 3.10 (2H, q, J = 7 Hz), 3.20 (1H, s), 6.30 (1H, d, J = 5 Hz), 6.63 (1H, m), 6.87 (1H, d, J = 5 Hz), 6.95 (1H, m), 7.60-7.73 (4H,m),8.79(lH,m). Example 615 To a solution of 5-[4-(3-cyanophenyl)-7-e1Hyl-2-phenylpyrrolo[l,2-b]pyridazin-3-yl]pentanoic acid(100 mg) in tetrydrofurane (1 mL) was added 1 M borane-tetrydrofurane comples (0.708 mL,) in an ice ba1H under a nitrogen atmosphere. 1He mixture was stirred for 4 hours in 1He ba1H and 1 hour at room temperature. 1He reaction was quenched by adding 1 N hydrochloric acid (1 mL). 1He mixture was partitioned between EtOAc (10 mL) and 1 N hydrochloric acid (5 mL). 1He organic layer was washed wi1H water and brine, dried over magnesium sulfate, and evaporated. Preparative 1Hin layer chromatography elutingwi1H acetone-hexane = 1-2 afforded 3-[7-e1Hyl-3-(5-hydroxypentyl)-2-phenylpyrrolo[l,2-b]pyridazin-4-yl]benzonitrile as an yellow gum (104 mg). 3-[7-e1Hyl-3-(5-hydroxypentyl)-2-phenylpyrrolo[l,2-b]pyridazin-4-yl]benzonitrile 1H-NMR (CDCl3) 5 0.98-1.17 (6H, m), 1.36 (1H, t, J = 7 Hz), 2.38 (2H, m), 258 (2H, m), 3.34 (2H, m), 5.89 (1H, d, J = 5 Hz), 6.62 (1H, d, J = 5 Hz), 7.45-7.53 (, m), 7.55-7.67 (4H,m). MS(ESI+):m/z410(M + H) 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Preparation 24. Preparation 343 e1Hyl 2-[(5-bromo-3-pyridiny])carbonyl]-4-melhoxy-3-oxobutanoate 1H NMR (CDC13) 6 0.96-1.10 (1H, m), 3.23 (1,, s), 3.49 (1., s), 4.00-4.34 (4H, m), 4.57 (1H, s), 8.00 (0., br s), 8.23 (0., br s), 8.60-8.91 (2H, m). Preparation 344 1-lert-butyl 8-e1Hyl 2-acetyl-2-[(6-cyano-3-pyridinyl)carbonyl]octanedioate 1H NMR (CDC13) 6 1.22-1.46 (16H,m), 1.55-1.70 (2H,m), 2.17-2.34 (4H,m),2.48 (1H, s), 4.14 (2H, q, J = 8 Hz), 7.77 (1H, br d, J = 8 Hz), 8.17 (1H, dd, J = 8, 2 Hz),8.97(lH,d,J = 2Hz). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Preparation 78. Preparation 345 e1Hyl 7-[(6-cyano-3-pyridinyl)carbonyl]-8-oxononanoate 1H NMR (CDCb) 5 1.20-1.45 (7H, m), 1.52-1.70 (2H, m), 1.92-2.14 (2H, m), 2.17-2.39 (, m), 4.11 (2H, q, J = 8 Hz), 4.40 (1H, t, J = 8 Hz), 7.84 (1H, br d, J = 8 Hz), 8.39 (1H, m), 9.23 (1H, br s). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Preparation 130. Preparation 346 e1Hyl 4-melhoxy-3-oxobutanoate 1H NMR (CDCb) 6 1.28 (1H, t, J = 8 Hz), 3.42 (1H, s), 3.51 (2H, s), 4.09 (2H, s), 4.20(2H,q,J = 8Hz). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Preparation 338. Preparation 347 benzyl 3-[(l-amino-5-e1Hyl-lH-pyrrol-2-yl)carbonyl]-5-bromobenzoate 1H-NMR (CDCl3) 8 1.28 (1H, t, J = 7 Hz), 2.75 (2H, q, J = 7 Hz), 5.37 (2H, s), 5.73 (2H, s), 5.94 (1H, d, J = 5 Hz), 6.66 (1H, d, J = 5 Hz), 7.35-7.48 (, m), 7.99 (lH,s), 8.33 (lH,s), 8.38 (lH,s). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Preparation 321. Preparation 348 benzyl 3-bromo-5-[(5-e1Hyl-1H-pyrrol-2-yl)carbonyl]benzoate 1H-NMR (CDCl3) 5 1.29 (1H, t, J = 7 Hz), 2.72 (2H, q, J = 7 Hz), 5.37 (2H, s), 6.09 (1H, m), 6.78 (1H, m), 7.33-7.45 (, m), 8.15 (1H, s), 8.33 (1H, s), 8.45 (1H, s). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Preparation 310. Preparation 349 benzyl 3-bromo-5-(chlorocarbonyI)benzoate Preparation 350 To a solution of benzyl 3-bromo-5-iodobenzoate (1.00 g) in 1HF (10 mL) was added 0.76 M isopropyl magnesium bromide (3.16 mL) in an ice ba1H under a nitrogen atmosphere. After stirring for 0.5 hour, 1He mixture was poured onto dryice. 1He mixture was warmed to room temperature over 1 hour. 1He mixture was partitioned between EtOAc and 1 N HC1. 1He organic layer was washed wi1H brine, dried over MgSCXi, and evaporated. Flash silicagel column chromatography (chloroform-me1Hanol = 50-0 to 50-2) afforded 3-benzyloxycarbonyl-5-bromobenzoic acid as a white solid (273 mg). 3-[(benzyloxy)carbonyl]-5-bromobenzoic acid 1H-NMR (DMSO-d6) 6 5.39 (2H, s), 7.30-7.52 (, m), 8.29 (2H, s), 8.43 (1H, s). Preparation 351 A mixture of 3-bromo-5-iodobenzoic aicd (5.00 g) and N,N-dime1Hylformamide (0.059 mL) in dichlorome1Hane (50 mL) was added oxalyl chloride (1.47 mL) in an ice ba1H under a nitrogen atmosphere. After stirring for 1 hour, 1He volatile was evaporated off. 1He residue was dissolved in dichlorome1Hane (50 mL), and to 1He solution was added bensyl alcohol (1.82 g) followe by trie1Hyl amine (3.2 mL) in 1He ice ba1H. 1He mixture was stirred for 2 hours at room temperature. 1He mixture was partitioned between EtOAc and water. 1He organic layer was washed wi1H water (two times), satd. NCO1H, and brine, dried over MgS04 and evaporated. Flash silicagel columnc hromatography (EtOAc-hexanes = 1/200 to 20/200) afforded benzyl 3-bromo-5-iodobenzoate as white crystals (5.95 g). benzyl 3-bromo-5-iodobenzoate 1H-NMR (CDCb) 6 535 (1H,s), 7.35-7.68 (,m), 8.04 (lH,s), 8.16 (lH,m), 8.30 (lH,s). 1He following compound(s) was(were) obtained in a similar manner to 1Hai of Example 1. Example 615 benzyl 3-bromo-5-[7-e1Hyl-2-me1Hyl-3-(me1Hylsulfonyl)pyrrolo[ 1,2-b]pyridazin-4-yljbenzoate 1H-NMR (CDC13) 6 1.38 (1H, t, J = 7 Hz), 2.88 (1H, s), 3.05 (1H, s), 3.06 (2H, q, J = 7 Hz), 5.35 (2H, s), 6.15 (1H, d, J = 5 Hz), 6.72 (1H, d, J = 5 Hz), 7.33-7.45 (, m), 7.68 (1H, m), 7.94 (1H, m), 8.28 (1H, m). Example 616 4-(3-cyanophenyl)-7-e1Hyl-2-phenylpyrrolo[l,2-b]pyridazine-3-carbonitrile 1H NMR (CDCl3) 8 1.42 (1H, t, J = 8 Hz), 3.12 (2H, q, J = 8 Hz), 6.60 (1H, d, J = 5 Hz), 6.92 (1H, d, J = 5 Hz), 7.50-7.58 (1H, m), 7.73 (1H, t, J = 8 Hz), 7.82-7.91 (1H, m), 7.93-8.01 (2H,m). Example 617 2-tert-butyl-4-(3-chlorophenyl)-7-e1Hylpyrrolo[l,2-b]pyridazine-3-carbonitrile 1H NMR (CDCl3) 8 1.38 (1H, t, J = 8 Hz), 1.60 (9H, s), 3,05 (2H, q, J = 8 Hz), 6.48 (1H, d, J = 5 Hz), 6.77 (1H, d, J = 5 Hz), 7.45-7.54 (1H, m), 7.60 (1H, br s). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Preparation 78. Example 618 e1Hyl 6-[4-(6-cyano-3-pyridinyl)-7-e1Hyl-2-me1Hylpyrrolo[ 1,2-b]pyridazin-3-yl1Hexanoate 1H NMR (CDC1.-,) 6 1.15-1.64 (12H, m), 2.21 (1H, t, J = 8 Hz), 2.32-2.44 (2H, m), 2.56 (1H, s), 3.01 (2H, q, J = 8 Hz), 4.10 (2H, q, J = 8 Hz), 5.79 (1H, d, J = 5 Hz), 6.54 (1H, d, J = 5 Hz), 7.85 (1H, br s), 8.30 (1H, br d, J = 8 Hz), 8.72 (1H, br s). MS(ESI+):m/z405(M + H). 1He following compound(s) was(were) obtained in a similar manner 1o 1Hai of Example 21. Example 619 e1Hyl 4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrrolo[l,2-b]pyridazine-3-carboxylate 1H NMR (CDCl3) 6 1.04 (1H, t, J = 8 Hz), 1.38 (1H, t, J = 8 Hz), 3.06 (2H, q, J = 8 Hz), 3.39 (1H, s), 4.10 (2H, q, J = 8 Hz), 4.76 (2H, s), 6.33 (1H, d, J = 5 Hz), 6.74 (1H, d, J = 5 Hz), 7.96 (1H, br s), 8.61 (1H, br s), 8.78 (1H, d, J = 2 Hz). MS (ESI+): m/z 418, 420 (M + H). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 76. Example 620 3-bromo-5-[7-e1Hyl-2-me1Hyl-3-(me1Hylsulfonyl)pyrrolo[l,2-b]pyridazin-4-yl]benzoic acid 1H-NMR (CDCl3 + CD30D) 6 1.38 (1H, t, J = 7 Hz), 2.86 (1H, s), 3.05 (1H, s), 3.06 (2H, q, J = 7 Hz), 6.19 (1H, d, J = 5 Hz), 6.71 (1H, d, J = 5 Hz), 7.53 (1H, s), 7.90 (1H,S),8.23(1H,S). Example 621 (2E)-3-[4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrrolo[l,2-b]pyridazin-3-yl]acrylic acid 1H NMR (CDCl3) 5 1.39 (1H, t, J = 8 Hz), 3.07 (2H, q, J = 8 Hz), 3.51 (1H, s), 4.65 (2H, s), 5.96 (1H, d, J = 15 Hz), 6.27 (1H, d, J = 5 Hz), 6.74 (1H, d, J = 5 Hz), 7.68 (1H, d, J = 15 Hz), 7.93 (1H, m), 8.57 (1H, d, J = 1 Hz), 8.70 (1H, d, J = 2 Hz). MS (ESI+): m/z 416,418 (M + H). Example 622 6-[4-(6-cyano-3-pyridiny])-7-e1Hy]-2-me1Hy]pyrro]o[ 1,2-b]pyridazin-3-y]1Hexanoic acid 1H NMR (CDCh) 5 1.15-1.69 (9H, m),l .90-2.50 (4H, m), 2.56 (1H, s), 3.01 (2H, q, J = 8 Hz), 5.80 (1H, d, J = 5 Hz), 6.51 (1H, d, J = 5 Hz), 7.84 (1H, dd, J = 8,2 Hz), 8.28 (1H, d, J = 8 Hz), 8.51 (1H, d, J = 2 Hz). MS (ESf): m/z 377 (M + H). Example 622-2 6-{4-[6-(aminocarbonyl)-3-pyridinyl]-7-e1Hyl-2-me1Hy]pynolo[l,2-b]pyridazin-3~ yl1Hexanoic acid 1H NMR (CDCl3) 6 1.16-1.51 (9H, m), 2.10-2.24 (2H, m), 2.35-2.47 (2H, m), 2.58 (1H, s), 3.01 (2H, q, J = 8 Hz), 5.85 (1H, d, J = 5 Hz), 6.54 (1H, d, J = 5 Hz), 7.22 (1H, br s), 7.90 (1H, dd, J = 8,1 Hz), 8.01 (1H, br s), 8.34 (1H, d, J = 8 Hz), 8.61 (lH,d,J = lHz). MS (ESI+): m/z 395 (M + H). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 147. Example 623 e1Hyl (2E)-3-[4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrrolo[l,2-b]pyridazin-3-yl]acrylate 1H NMR (CDCl3) 6 1 -27 (1H, t, J = 8 Hz), 1.39 (1H, t, J = 8 Hz), 3.06 (2H, q, J = 8 Hz), 3.51 (1H, s), 4.17 (2H, q, J = 8 Hz), 4.64 (2H, s), 5.97 (1H, d, J = 15 Hz), 6.24 (1H, d, J = 5 Hz), 6.73 (1H, d, J = 5 Hz), 7.51 (1H, d, J = 15 Hz), 7.91 (1H, br s), 8.57 (1H, br s), 8.70 (1H, br s). MS (ESI+): m/z 444,446 (M + H). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 200. Example 624 [4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrrolo[l,2-b]pyridazin-3-yl]me1Hanol 1H NMR (CDCl3) 5 1.38 (1H, t, J = 8 Hz), 3.05 (2H, q, J = 8 Hz), 3.45-3.55 (4H, m), 4.40 (2H, br d, J = 7 Hz), 4.77 (2H, br s), 6.22 (1H, d, J = 5 Hz), 6.70 (1H, d, J = 5 Hz), 8.11 (1H, m), 8.74 (1H, br s), 8.80 (1H, d, J = 2 Hz). MS (ESI+): m/z 376,378 (M + H). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 205. Example 625 (4E)-5-[4-(2-chloro-4-pyridinyl)-7-e1Hyl-2-me1Hylpyrrolo[l,2-b]pyridazin-3-yl]-4-pentenoic acid 1H NMR (CDCb) 6 1.37 (1H, l, J = 8 Hz), 2.26-2.43 (4H, m), 2.50 (1H, s), 3.01 (2H, q, J = 8 Hz), 5.40 (1H, dt, J = 15, 7 Hz), 6.05 (1H, d, J = 5 Hz), 6.20 (1H, d, J = 15 Hz), 6.56 (1H, d, J = 5 Hz), 7.28 (1H, br d, J = 5 Hz), 7.39 (1H, br s), 8.47 (1H, brd,J = z). MS (ESI+): m/z 370 (M + H). Example 625-2 (4Z)-5-[4-(2-chloro-4-pyridinyl)-7-e1Hyl-2-me1Hylpyrrolo[l,2-b]pyridazin-3-yl]-4-pentenoic acid 1H NMR (CDC13) 6 1.39 (1H, t, J = 8 Hz), 1.87-2.00 (2H, m), 2.12 (2H, t, J = 8 Hz), 2.42 (1H, s), 3.03 (2H, q, J = 8 Hz), 5.58 (1H, dt, J = 10, 8 Hz), 6.17 (1H, d, J = 5 Hz), 6.26 (1H, br d, J = 10 Hz), 6.60 (1H, d, J = 5 Hz), 7.35 (1H, br d, J = 5 Hz), 7.44 (1H, br s), 8.48 (1H, br d, J = 5 Hz). MS (ESI+): m/z 370 (M + H). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 220. Example 626 4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrrolo[l,2-b]pyridazine-3-carboxylic acid 1H NMR (CDCl3) 6 1.39 (1H, t, J = 8 Hz), 3.06 (2H, q, J = 8 Hz), 3.44 (1H, s), 4.82 (2H, s), 6.36 (1H, d, J = 5 Hz), 6.77 (1H, d, J = 5 Hz), 8.09 (1H, br s), 8.65 (1H, brs),8.72(lH,brs). MS (ES1+): m/z 390, 392 (M + H). Example 627 4-(2-chloro-4-pyridinyl)-7-e1Hyl-2-me1HyIpyrroIo[l ,2-b]pyridazine˚3-carboxyIic acid 1H NMR (CDCl3) 6 138 (1H,t, J = 8 Hz), 2.70 (1H, s), 3.06 (2H, q, J = 8 Hz), 6.26 (lH,d,J = z),6.72(lH,d,J=z),7.32(lH,dd,J = 5J Hz),7.43 (lH,br s),8.50(lH,d,J=z). MS(ESI+):m/z316(M+H). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 244. Example 628 4-(2-chloro-4-pyridinyl)-7-elhyl-2-me1Hylpyrrolo[l,2-b]pyridazine-3-carbaldehyde 1H NMR (CDCl3) 6 1.39 (1H, t, J = 8 Hz), 2.81 (1H, s), 3.09 (2H, q, J = 8 Hz), 6.43 (1H, d, J = 5 Hz), 6.78 (1H, d, J = 5 Hz), 7.34 (1H, br d, J = 5 Hz), 7.46 (1H, br s), 8.56 (1H, d, J = 5 Hz), 9.76 (1H, s). MS (ESI˚): m/z 300 (M + H). Example 629 4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrrolo[l,2-b]pyridazine-3- carbaldehyde 1H NMR (CDCl3) 6 1.41 (1H, t, J = 8 Hz), 3.14 (2H, q, J = 8 Hz), 3.55 (1H, s), 4.94 (2H, s), 6.50 (1H, d, J = 5 Hz), 6.84 (1H, d, J = 5 Hz), 7.95 (1H, br s), 8.12 (1H, br s), 8.84 (1H, br s), 9.85 (1H, s). MS (ESf): m/z 374,376 (M + H). Example 630 A solution of phosphorus oxychloride (241 mg, 1.57 mmol) in N,N-dime1Hylformamide (4 mL) was stirred for 10 min at room temperature. 1He resulting mixture was cooled to 0°C, and a solution of e1Hyl 4-(4~fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazine-3-carboxylate (428 mg, 1.31 mmol) in N,N-dime1Hylformamide (0.7 mL) was added. 1He resulting mixture was warmed to 50°C, and stirred for 45 min. Since 1He startimg material was remained, a solution of phosphorus oxychloride (621 mg, 0.67 mmol) in N,N-dime1Hylformamide (0.2 mL) was added, and 1He mixture was stirred for 15 min. 1He resulting mixture was poured into ice-cooled water (10 mL), and extracted wi1H e1Hyl acetate (30 mL). 1He organic layer was washed wi1H water and saturated sodium bicarbonate. All 1He aqueous layer was extracted wi1H e1Hyl acetate. 1He combined organic extract was washed wi1H brine, dried over anhydrous magnesium sulfate, and evaporated to give a blue oil. Flash silica gel column chromatography eluting wi1H e1Hyl acetate-hexane = 1-20 to 1-10 afforded e1Hyl 4-(4-fluorophenyl)-7-formyl-2-isopropyIpyrroIo[ 1,2-b]pyridazine-3-carboxylate as an yellow oil, which was crystalized upon standing (360 mg, 77.5%). 1H-NMR (CDC13) 5 1.02 (1H, t, J = 7 Hz), 1.41 (6H, d, J = 7 Hz), 3.29 (1H, septet, J = 7 Hz,), 4.10 (2H5 q, J = 7 Hz), 6.42 (1H, d, J = 5 Hz), 7.20 (2H, t, J = 9 Hz), 7.45 - 7.51 (1H, m), 10.56 (1H ,s). MS(ESI+):m/z355(M + H) Example 631 To a solution of N,N-dime1Hylacetamide (80.1 mg, 0.919 mmol) in dichloroe1Hane (1 mL) was added phosphorus oxychloride (141 mg, 0.919 mmol) in dichloroe1Hane (0.5 mL) at 0°C. After stirring for 0.5 h, a solution of e1Hyl 4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazine-3-carboxylate (200 mg, 0.613 mmol) in dichloroe1Hane(0.5 mL) was added. 1He resulting mixture was stirred for 3 days at room temperature. 1He mixture was partitioned between e1Hyl acetate (30 mL) and water (5 mL), and 1He organic layer was washed wi1H saturated sodium bicarbonate, brine, dried over anhydrous magnesium sulfate, and evaporated to give an orange gum. Flash silica gel column chromatography eluting wi1H e1Hyl acetate-hexane = 1-20 to 1-10 afforded e1Hyl 7-acetyl-4-(4-fluorophenyl)-2-isopropylpyrrolo[l ,2-b]pyridazine-3-carboxylate as an yellow gum (144 mg, 63.8%). 1H-NMR (CDCl3) 6 1.00 (1H, t, J = 7 Hz), 1.41 (6H, d, J = 7 Hz), 2.88 (1H, s), 3.09 (1H, septet, J = 7 Hz), 4.09 (2H, q, J = 7 Hz), 6.40 (1H, d, J = 5 Hz), 7.19 (2H, t, J = 9 Hz), 7.46 (2H, dd, J = 3 and 9 Hz), 7.57 (2H, d, J = 7 Hz). MS(ESf):m/z369(M + H) Example 632 A solution of e1Hyl 4-(4-fluorophenyl)-7-formyl-2-isopropy]pyrrolo[l,2- b]pyridazine-3-carboxyIale (100 mg, 0.282 mmol) and sodium borohydride (10.7 mg, 0.282 mmol) in e1Hanol (1 roL) was stirred for 0.5 h under an ice ba1H. 1He mixture was partitioned between e1Hyl acetate (10 mL) and water (5 mL), and 1He organic layer was cashed wi1H brine, dried over anhydrous magnesium sulfate, and evaporateed to give s1Hyl 4-(4-fluorophenyl)-7-hydroxyme1Hyl-2-isopropylpyrrolo[l,2-b]pyridazine-3-1Harboxylate as an yellow gum (89.1 mg, 89.1%). 1H-NMR (CDC13) 5 0.97 (1H, t, J = 7 Hz), 1.37 (6H,, J = 7 Hz), 3.25-3.37 (2H, m), 4.04 (2H, q, J = 7 Hz), 5.06 (1H, d, J = 7 Hz), 6.32 (1H, d, J = 5 Hz), 6.78 (1H, d, J = 5 Hz), 7.19 (2H, t, J = 9 Hz), 7.46 (2H, d, J = 4 and 9 Hz). Example 633 To a solution of e1Hyl 4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazine-3-carboxylate (80.0 mg, 0.245 mmol) and N,N-dime1Hylaminopyridine (29.9 mg, 0.245 mmol) in N,N-dime1Hylformamide (0.5 mL) was added 3,7-dinitro-5-(trifluorome1Hyl)dibenzo[b,d]1Hiophenium trifluorome1Hanesulfonate (120 mg, 0.245 mmol) at -20°C. 1He resulting mixture was stirred for 45 min at 0°C and 12 h at room temperatue. Water (5 mL) and e1Hyl acetate (10 mL) were added, and 1He resulting mixture was filtered. 1He organic layer was washed wi1H brine, dried over anhydrous magnesium sulfate, and evaporated to give a brown gum. Flash silica gel column chromatography eluting wi1H toluene-hexane = 1-5 to 4-5 afforded e1Hyl 4-(4-fluorophenyl)-2-isopropyl-7-trifluorome1Hylpyrrolo[l,2-b]pyridazine-3-carboxylate product as an yellow gum (46.7 mg, 48.3%). 1H-NMR (CDCl3) 6 1.00 (1H, t, J = 7 Hz), 1.38 (6H, d, J = 7 Hz), 3.26 (1H, septet, J = 7 Hz), 4.08 (2H, q, J = 7 Hz), 6.33 (1H, d, J = 5 Hz), 7.12 (1H, d, J = 5 Hz), 7.19 (2H, t, J = 9 Hz), 747 (2H, d, J = 4 and 9 Hz). MS (ESf): m/z 395 (M + H) Example 634 A solution of e1Hyl 4-(4-fluorophenyl)-7-formyl-2-isopropyIpyrroIo[l ,2-b]pyridazine-3-carboxylate (200 mg, 0.564 mmol), hydroxylamine hydrochloride (51.0 mg, 0.734 mmol), and sodium formate (69.1 mg, 1.02 mmol) in formic acid (2 mL) were refluxcd for 2 h. 1He mixture was evaporated to give a green gum. 1He gum was partitioned between e1Hyl acetate (10 mL) and saturated sodium bicarbonate (5 mL). 1He organic layer was washed wi1H brine, dried over anhydrous magnesium sulfate, and evaporated to give a green gum. Flash silica gel column chromatography eluting wi1H e1Hyl acetate-hexane = 1-10 to 1-8 gave e1Hyl 7-cyano-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazine-3-carboxylate as an yellow crystal (144 mg, 72.6%). 1HNMR (CDCb) 5 1.01 (1H, t, J = 7 Hz), 1.41 (6H, d, J = 7 Hz), 3.26 (1H, septet, J = 7 Hz), 4.09 (2H, q, J = 7 Hz), 636 (1H, d, J = 5 Hz), 7.20 (2H, t, J = 9 Hz), 7.28 (1H, d, J = 5 Hz), 7.47 (2H, d, J = 4 and 9 Hz). MS (ESI+): m/z 398 (M + HCOOH + H) Example 635 A solution of e1Hyl 7-cyano-4-(4-fluorophenyl)-2-isopropylpyrrolo[l ,2-b]pyridazine-3-carboxylate (70.4 mg, 0.200 mmol) in sulfuric acid (1 mL) was stirred for 50 min at 70°C. 1He solution was partitioned between e1Hyl acetate and water. 1He organic layer was washed wi1H brine, dried over anhydrous magnesium sulfate, and evaporated to give a brown gum. Preparative silica gel 1Hin layer chromatography eluting wi1H e1Hyl acetate-hexane = 1-1 afforded e1Hyl 7-aminocarbonyl-4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazine-3-carboxylate as an orange solid (5.2 mg, 7.0%). 1H-NMR (CDC13) 6 0.99 (1H, t, J = 7 Hz), 1.41 (6H, d, J = 7 Hz), 3.41 (1H, septet, J = 7 Hz), 4.08 (2H, q, J = 7 Hz), 5.93 (1H, br s), 6.46 (1H, d, J = 5 Hz), 7.45 (2H, t, J = 9 Hz), 7.28 (1H, d, J = 5 Hz), 8.90 (1H, br s). Example 636 To a mixture of e1Hyl 4-(4-fluorophenyl)-2-isopropylpyrrolo[l,2-b]pyridazine-3-carboxylate (100 mg, 0.306 mmol) and ammonium 1Hiocyanate (28.0 mg, 0.368 mmol) in me1Hanol (100 mL) was added cerium ammonium nitrate (386 mg, 0.705 mmol) under an ice ba1H. 1He mixture was stirred for 30 min. 1He mixture was stirred for additional 10 min after adding ammonium 1Hiocyanate (8.2 mg, 0.107 mmol). Water (5 mL) was added, and 1He mixture was extracted wi1H e1Hyl acetate (20 mL). 1He organic extract was washed wi1H brine, dried over anhydrous magnesium sulfate, and evaporated to give a deep green gum. Flash silica gel column chromatography eluting wi1H e1Hyl acetate-hexane = 1-10 to 3-20 afforded e1Hyl e1Hyl 4-(4-fluorophenyl)-2-isopropyl-7-1Hiocyanatopyrrolo[l,2-b]pyridazine3-carboxylale as an yellow gum (89.6 mg, 82.3%). 1H-NMR (CDCb) 5 1.01 (1H, t, J = 7 Hz), 1.46 (6H, d, J = 7 Hz), 3.36 (1H, septet, J = 7Hz),4.08(2H,q,J = 7Hz),6.23(1H,d,J = 5 Hz), 7.14-7.22 (1H,m), 7.16 (2H, t, J = 9 Hz), 7.46 (2H, dd, J = 4 and 9 Hz). Example 637 To a solution of e1Hyl 4-(4-fluorophenyl)-2-isopropyl-7-1Hiocyanatopyrrolo[l,2-b]pyridazine-3-carboxylate (77.7 mg, 0219 mmol) in me1Hanol (0.7 mL) was added 85% potassium hydroxide (0.3 mg, 0.004 mmol) at room temperature. After stirring for 5 min, 1He mixture was partitioned between e1Hyl acetate (20 mL) and water (5 mL). 1He organic layer was washed wi1H brine, dried over anhydrous magnesium sulfate, and evaporated to give an yellow gum. Preparative silica gel 1Hin layer chromatography eluting wi1H e1Hyl acetate-hexane = 1-7 afforded e1Hyl 4-(4-fluorophenyl)-2-isopropyl-7-(me1Hyl1Hio)pyrrolo[l32-b]pyridazine-3-carboxylate as an yellow gum (35.9 mg, 44.1%). 1H-NMR (CDC13) 5 0.98 (1H, t, J = 7 Hz), 1.41 (6H, d, J = 7 Hz), 2.52 (1H, s), 3.32 (1H, septet, J = 7 Hz), 4.05 (2H, q, J = 7 Hz), 6.35 (1H, d, J = 5 Hz), 6.89 (1H, d, J = 5 Hz), 7.16 (2H, t, J = 9 Hz), 7.44 (2H, d, J = 4 and 9 Hz). MS (ESf): m/z 373 (M + H) 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 1 Example 638 3-(9-e1Hyl-3-me1Hoxy-5,6-dihydrobenzo[f]pyrrolo[l,2-b]cinnolin-12-yl)benzonitrile 1HNMRCCDCL3) 6 1-41 (1H,t,J = 8 Hz), 2.91-3.11 (6H,m), 3.78 (1H,s), 6.09 (1H, d, J = 5 Hz), 6.38 (1H, dd, J = 8,3 Hz), 6.52 (1H, d, J = 8 Hz), 6.59 (1H, d, J = 5 Hz), 6.77 (1H, br s), 7.56 (1H, t, J = 8 Hz), 7.67 (1H, br d, J = 8 Hz), 7.70-7.77 (2H,m). Example 639 4-(3-e1Hy]-6H-indeno[l,2-e]pyrrolo[J,2-b]pyridazin-ll-y])benzonitri]e 1H NMR (CDCl3) 6 1.43 (1H, t, J = 8 Hz), 3.09 (2H, q, J = 8 Hz), 4.11 (1H, s), 6.14 (1H, d, J = 5 Hz), 6.64 (1H, d, J = 5 Hz), 6.71 (1H, d, J = 8 Hz), 7.07 (1H, I, J = 8 Hz), 7.20-7.30 (1H, overlapped wi1H CDCl3), 7.49 (1H, d, J = 8 Hz), 7.69 (2H, d, J = 8Hz),7.88(2H,d,J = 8Hz). MS(ESl+):m/z336(M + H). 1He following compound(s) was(were) obtained in a similar manner to 1Hai of Preparation 24. Preparation 352 e1Hyl 4-me1Hoxy-2-[(5-me1Hyl-3-pyridinyl)carbonyl]-3-oxobutanoate 1H NMR (CDCl3) 6 0.97,1.26 (1H, t, J= 7 Hz), 2.40 (1H, s), 3.24,3.35,3.49 (1H, s), 3.98-4.20 (2H, m), 4.11,4.20,4.54 (2H, s), 5.70 (1H, s), 7.67,7.92,8.02, 8.50- 8.66, 8.77, 8.89 (1H,m). Preparation 353 e1Hyl 2-[(5-chloro-3-pyridinyl)carbonyl]-4-me1Hoxy-3-oxobutanoate 1H NMR (CDCl3) 5 1.00,1.06, 1.28,1.35 (1H, t, J= 7 Hz), 3.23, 3.43,3.49 (1H, s), 4.05-4.33 (2H, m), 4.56 (2H, s), 7.85, 8.05, 8.22, 8.29, 8.58-8.82,8.85,9.01, 9.10 (1H,m). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Preparation 176. Preparation 354 tert-butyl 3-bromo-5-({l-[(cyanoacetyl)amino]-5-e1Hyl-lH-pyrrol-2-yl}carbonyl)benzoate 1HNMR (CDCl3) 6 1.29 (34H, t, J = 7 Hz), 1.60 (9H, s), 2.61 (2H, q, J = 7 Hz), 3.64 (2H, s), 6.00 (1H, m), 6.80 (1H, m), 8.03 (1H, m), 8.26 (1H, m), 8.28 (1H, m). Preparation 355 tert-butyl 3-bromo-5-[(5-e1Hyl-l-{[(me1Hylsulfonyl)acetyl]amino}-lH-pyrrol-2- yl)carbonyl]benzoate 1H-NMR(CDCl3)6 1.29(1H,t,J=7Hz), 1.60(9H,s),2.60(2H,q,J = 7 Hz),2.92 (1H, s), 4.04 (2H,s), 6.11 (1H,m), 6.78 (lH,m), 8.03 (lH,m), 8.25 (J H,m), 8.27 (lH,m). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Preparation 153. Preparation 356 tert-butyl 3-bromo-5-(chlorocarbonyl)benzoate 1He following cornpound(s) was(were) obtained in a similar manner to 1Hat of Preparation 164. Preparation 357 tert-butyl 3-bromo-5-[(5-e1Hyl-lH-pyrrol-2-yl)carbonyl]benzoate 1H-NMR (CDC13) 6 1.32 (1H, t, J = 7 Hz), 1.61 (9H, s), 2.74 (2H, q, J = 7 Hz), 6.10 (1H, m), 6.80 (1H, m), 8.13 (1H, m), 8.26 (1H, m), 8.39 (1H, m), 9.34 (1H, s, br). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Preparation 338. Preparation 358 tert-butyl 3-[(l1HaMIo-5-e1Hyl-lH-pyrrol-2-yl)carbonyl]-5-bromobenzoate 1H -NMR (CDCb) 5 1.29 (1H, t, J = 7 Hz), 1.61 (9H, s), 2.76 (2H, q, J = 7 Hz), 5.74 (2H, s, br), 5.93 (1H, d, J = 5 Hz), 6.63 (1H, d, J = 5 Hz), 8.05 (1H, m), 8.25 (1H, m),8.29(lH,m). Preparation 359 To a solution of tert-butyl 3-bromo-5-iodobenzoate (4.00 g) in tetrydrofuran (30 mL) was added 0.76 M isopropylmagnesium bromide (13.7 mL) in an ice-me1Hanol ba1H under a nitrogen atmosphere. After stirring for 0.5 hour, 1He mixture was poured onto dryice. 1He mixture was warmed to room temperature over 1 hour. 1He mixture was partitioned between EtOAc and 1 N hydrochloric acid. 1He organic layer was back extracted wi1H 1 N sodium hydroxide (two times). 1He extract was acidified by adding concentrated hydrochloric acid, and extracted wi1H chloroform (two times). 1He organic extract was washed wi1H brine, dried over MgSO4, and evaporated to give 3-bromo-5-(lert-butoxycarbonyl)benzoic acid as a pale brown solid (529 mg). 5-bromo-5-(tert-butoxycarbonyl)bcnzoic acid 1H -NMR (DMSOd6) 6 1.57 (9H, s), 8.21 (1H, s), 8.25 (1H, s), 837 (1H, s). Preparation 360 To a vigirously stirred suspension of pondered MgSO4 (7.36 g) in dichlorome1Hane (50 mL) was added sulfuric acid (0.758 mL) at room temperature. After stirring for 15 minutes, to 1He mixture was added 3-bromo-5-iodobenzoic acid (5.00 g) followed by tert-butanol (7.31 mL). 1He mixture was stirred for 3 days at room temperature. 1He mixture was partitioned between EtOAc and water. 1He organic layer was washed wi1H satd. NCCb and brine, dried over MgS04, and evaporated to give tert-butyl 3-bromo-5-iodobenzoate as pale purple crystals (4.44 g). tert-butyl 3brorno-5-iodobenzoate 1H-NMR (CDC13) 6 1.58 (9H, s), 8.00 (1H, m), 8.06 (1H, m), 8.22 (1H, m). Preparation 361 To a suspension of li1Hium (316 rng) in e1Her (10 mL) was added cyclopropylbromide (2.50 g) in e1Her (10 mL) over 20 min in a me1Hanol-ice ba1H under a nitrogen atmosphere. 1He mixture was stirred for 0.5 hour in an ice ba1H. 1He mixture was cooled in a dryice-acetone ba1H. To 1He mixture was added a solution of triisopropoxyborane (5.05 g) in tetrydrofuran (5 mL) over 15 minutes. 1He mixture was alowed to warme to room temperature over 2 hours. 1He reaction was quenced by adding hydrochloric acid. 1He organic solvent was evaporated off, and 1He residual solution was extracted wi1H e1Her (30 mL, five times). 1He combined extract was dried over MgS04, and evaporated to give a white solid (968 mg). 1He solid was triturated in cold hexanes to give cyclopropylboronic acid as a white powder (789 mg). cyclopropylboronic acid 1H-NMR (DMSO-d6) 6 -0.40 (1H, m), 032 (2H, m), 0.39 (2H, m), 7.28 (2H, s). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 21. Example 640 e1Hyl 7-e1Hyl-2-(me1Hoxymelhyl)-4-(5-melhyl-3-pyridinyl)pynolofl,2-b]pyritlazine-3- carboxylate 1H NMR (CDC1..) 5 0.99 (1H, t, J= 7 Hz), 1.38 (1H, t, J= 7 Hz), 2.41 (1H, s), 3.06 (2H, q, J= 7 Hz), 3.38 (1H, s), 4.06 (2H, q, J= 7 Hz), 4.75 (2H, s), 6.33 (1H, d, J= 4 Hz), 6.71 (1H, d, J= 4 Hz), 7.61 (1H, s), 8.52 (1H, d, J= 2 Hz), 8.54 (1H, d, .1= 2 Hz). MS(ESI+):m/z354. Example 641 e1Hyl 4-(5-chloro-3-pyridinyl)-7-e1Hyl-2-(me1HoxyjTie1Hyl)pyrrolo[l,2-b]pyridaziiie-3- carboxylate 1H NMR (300 MHz, CDClj) 5 1.04 (1H, t, J = 7 Hz), 1.38 (1H, t, J = 7 Hz), 3.06 (2H, q, J = 7 Hz), 3.39 (1H, s), 4.09 (2H, q, J = 7 Hz), 4.76 (2H, s), 6.33 (1H, d, J = 4 Hz), 6.75 (1H, d, J = 4 Hz), 7.81 (1H, dd, J = 2, 2 Hz), 8.57 (1H, d, J = 2 Hz), 8.68(lH,d,J = 2Hz). MS(m/z)374(M+l). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 076. Example 642 (2E)-3-[7-e1Hyl-2-(me1Hoxyme1Hyl)-4-(5-me1Hyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]acrylic acid 1H NMR (CDCl3) 6 1.39 (1H, t, J= 7 Hz), 2.43 (1H, s), 3.07 (2H, q, J= 7 Hz), 3.51 (1H, s), 4.65 (2H, s), 5.97 (1H, d, J= 16 Hz), 6.27 (1H, d, J= 4 Hz), 6.71 (1H, d, J= 4 Hz), 7.61 (1H, s), 7.72 (1H, d, J= 16 Hz), 8.46 (1H, d, J= 2 Hz), 8.57 (1H, d, J=2Hz). MS (ES1+): m/z 352. Example 643 (2E)-3-[4-(5-chloro-3-pyridinyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrrolo[l,2-b]pyridazin-3- yl]acrylic acid 1H NMR (300 MHz, CDC13) 6 1.39 (1H, t, J = 7 Hz), 3.07 (2H, q, J = 7 Hz), 3.51 (1H, s), 4.65 (2H, s), 5.97 (1H, d, J = 16 Hz), 6.27 (1H, d, J = 4 Hz), 6.75 (1H, d, J = 4 Hz), 7.69 (1H, d, J = 16 Hz), 7.78 (1H, dd, J = 2, 2 Hz), 8.54 (1H, d, J - 2 Hz), 8.71 (lH,d,J = 2Hz). MS(m/z)400(M+l). Example 644 4-[4-(5-cyclopropyl-3-pyridinyl)-7-e1Hyl-2-(me1Hoxymc1Hyl)pyrrolo[l,2-b]pyridazin-3- yl]butanoic acid 1H-NMR (CDC13) 6 0.78 (2H, m), 1.10 (2H, m), 1.37 (1H, t, J = 7 Hz), 1.73 (2H, m), 1.98 (1H, m), 2.23 (2H, m), 2.62 (2H, m), 3.02 (2H, q, J = 7 Hz9, 3.46 (1H, s), 4.65 (2H, q, J = 7 Hz), 5.88 (1H, d, J = 5 Hz), 6.57 (1H, d, J = 5 Hz), 7.36 (1H, m), 8.41 (lH,m), 8.47 (lH,m). Example 645 5-[4-(5-cyclopropyl-3-pyridinyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrrolo[l,2-b]pyridazin-3' yl]pentanoic acid 1H-NMR (CDCl3) 5 0.75 (2H, m), 1.08 (2H, m), 1.37 (1H, t, J = 7 Hz), 1.40-1.57 (4H, m), 1.96 (1H, m), 2.18 (2H, m), 2.51 (2H, m), 3.02 (2H, q, J = 7 Hz), 3.45 (1H, s), 4.61 (2H, m), 5.87 (1H, d, J = 5 Hz), 6.56 (1H, d, J = 5 Hz), 7.34 (1H, m), 8.39 (lH,m),8.50(lH,m). Example 646 3-[4-(5-cyclopropyl-3-pyridinyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrrolo[l,2-b]pyridazin-3- yljpropanoic acid 1H-NMR (DMS0-d6) 6 0.76 (2H,m) ,1.08 (2H, m), 1.37 (1H, t, J = 7 Hz), 1.95 (1H, m), 2.48 (2H, m), 2.87 (2H, m), 3.02 (2H, q, J = 7 Hz), 3.47 (1H, s), 4.66 (2H, m), 5.90 (1H, d, J = 5 Hz), 6.59 (1H, d, J = 5 Hz), 7.35 (1H, m), 8.40 (1H, m), 8.48 (lH,m). Example 647 5-[4-(2-chloio-4-pyridinyl)-7-e1Hyl-2-me1Hy]pyrrolo[l,2-b]pyridazin-3-yl]-5-oxopentanoic acid 1H NMR (CDCb) 8 1.38 (1H, t, J = 8 Hz), 1.73-1.85 (2H, m), 2.26 (2H, t, J = 8 Hz), 2.36 (2H, t, J = 8 Hz), 2.46 (1H, s), 3.04 (2H, q, J = 8 Hz), 6.33 (1H, d, J = 5 Hz), 6.70(lH,d,J=z),7.34(1H,brd),7,45(lH,brs),81H3(lH,d,J = 6Hz). Example 648 (2E)-3-[4-(2-chloro-4-pyridiny])-7-e1Hyl-2-me1Hylpyrrolo[l,2-b]pyridazin-3-y]Jacrylic acid 1H NMR (CDC13) 6 1.38 (1H, t, J = 8 Hz), 2.67 (1H, s), 3.05 (2H, q, J = 8 Hz), 5.79 (1H, d, J = 15 Hz), 6.19 (1H, d, J = 5 Hz), 6.67 (1H, d, J = 5 Hz), 7.24-7.29 (1H, overlapped wi1H CDC13), 7.40 (1H, br s), 7.51 (1H, d, J = 15 Hz), 8.55 (1H, d, J = 5 Hz). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 146. Example 649 e1Hyl (2E)-3-[4-(2-chloro-4-pyridinyl)-7-e1Hyl-2-melhylpyrrolo[l,2-b]pyridazin-3-yljacrylate 1H NMR (CDC13) 6 1.27 (1H, t, J = 8 Hz), 1.38 (1H, t, J = 8 Hz), 2.65 (1H, s), 3.04 (2H,q,J = 8Hz),4.17(2H,q,J = 8Hz),5.76(lH,d,J = 15 Hz),6.16 (1H,d,J = 5 Hz), 6.65 (1H, d, J = 5 Hz), 7.24-7.29 (1H, overlapped wi1H CDC13), 7.40 (1H, br s), 7.53 (1H, d, J = 15 Hz), 8.53 (1H, d, J = 5 Hz). MS (ES1+): m/z 370 (M + H). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 181. Example 650 tert-butyl 3-bromo-5-(3-cyano-7-e1Hyl-2-oxo-l,2-dihydropyrrolo[l ,2-b]pyridazin-4-yl)benzoate 1H-NMR (CDCl3) 6 1.36 (1H, t, J = 7 Hz), 2.94 (2H, q, J = 7 Hz), 6.57 (1H, d, J = 5 Hz), 6.72 (1H, d, J = 5 Hz), 7.94 (1H, m), 8.20 (1H, m), 8.38 (1H, m). Example 651 tert-butyl 3-bromo-5-[7-e1Hyl-3-(me1Hylsulfonyl)-2-oxo-l,2-dihydropyrrolo[l,2- b]pyridazin-4-yl]benzoate 1H-NMR (CDCl3) 6 1.35 (1H, 1, J = 7 Hz), 3.02 (2H, q, J = 7 Hz), 3.06 (1H, s), 6.24 (1H, d, J = 5 Hz), 6.70 (J H,d,J = 5 Hz), 7.23 (1H, m), 7.94 (1H, m), 8.25 (1H, m). 1He following compound(s) was(were) obtained in a similar manner lo 1Hat of Example 183. Example 652 tert-butyl 3-bromo-5-(3-cyano-7-e1Hyl-2-{[(trifluorome1Hyl)sulfonyl]oxy}pyrrolo[l,2-b]pyridazin-4-yl)benzoate 1H-NMR (CDCl3) 5 139 (1H, t, J = 7 Hz), 1.61 (9H, s), 3.02 (2H, q, J = 7 Hz), 6.81 (1H, d, J = 5 Hz), 700 (1H, d, J = 5 Hz), 7.96 (1H, m), 8.21 (1H, m), 8.33 (1H, m). Example 653 tert-butyl 3-bromo-5-(7-e1Hyl-3-(me1Hylsulfonyl)-2- {[(trifluorome1Hyl)sulfonyl]oxy}pyirolo[l,2-b]pyridazin˚4»yl)benzoate 1H-NMR (CDCl3) 5 1.38 (1H, t, J = 7 Hz), 1.59 (9H, s), 3.01 (2H, q, J = 7 Hz), 3.22 (1H, s), 6.46 (1H, d, J = 5 Hz), 7.12 (1H, d, J = 5 Hz), 7.67 (1H, m), 7.90 (1H, m), 8.23 (lH,m). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 184. Example 654 tert-butyl 3-bromo-5-[3-cyano-7-e1Hyl-2-(l -pyrrolidinyl)pyrrolo[l,2-b]pyridazin-4-yl]benzoate 1H-NMR (CDCb) 5 1.35 (1H, t, J = 7 Hz), 1.60 (9H, s), 2.01 (4H, m), 2.93 (2H, q, J = 7 Hz), 3.73 (4H, m), 6.32 (1H, d, J = 5 Hz), 6.58 (1H, d, J = 7 Hz), 7.86 (1H, m), 8.12 (lH,m), 8.24 QH,m). Example 655 tert-butyl 3-bromo-5-[7-e1Hyl-3-(me1Hylsulfonyl)-2-(l-pyrrolidinyl)pyrrolo[l,2- b]pyridazin-4-yl]benzoate 1H-NMR(CDCl3)51.37(1H,t,J = 7Hz),1.58(9H,s),1.99(4H,m),2.98(2H,q,J = 7 Hz), 3.21 (1H, s), 3.52 (4H, m), 6.30 (1H, d, J = 5 Hz), 6.66 (1H, d, J = 5 Hz), 7.76 (lH,m), 8.00 (lH,m), 8.19 (1H,m). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 147. Example 656 e1Hyl (2E)-3-[4-(5-chloro-3-pyridinyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrrolo[l,2- b]pyridazin-3-yl]acrylate 1H NMR (300 MHz, CDCl3) 5 1.27 (1H, l, J = 7 Hz), 1.39 (1H, t, J = 7 Hz), 3.07 (2H, q,J =7Hz),31H1(1H,s),4.18(2H,q,J=7Hz),4.64(2H,s),5.97(lH,d,J = 16 Hz), 6.24 (1H, d, J = 4 Hz), 6.72 (1H, d, J = 4 Hz), 7.61 (1H, d, J = 16 Hz), 7.76 (1H, dd, J = 2,2 Hz), 8.54 (1H, d, J = 2 Hz), 8.68 (1H, d, J = 2 Hz). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 205. Example 657 (4E)-5-[4'(5-chloro-3-pyridinyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrrolo[l,2-b]pyridazin-3-yl]-4-pentenoic acid 1H NMR (300 MHz, CDC13) 6 138 (1H, t, J = 7 Hz), 2.25-2.41 (4H, m), 3.05 (2H, q, J = 7 Hz), 3.50 (1H, s), 4.57 (2H, s), 5.53 (1H, dd, J = 16,7 Hz), 6.13 (1H, d, J = 4 Hz), 6.36 (1H, d, J = 16 Hz), 6.65 (1H, d, J = 4 Hz), 7.80 (1H, s), 8.54 (1H, br s), 8.62(lH,brs). MS(m/z)400(M+l). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Preparation 153. Example 658 4-(2-chloro-4-pyridinyl)-7-e1Hyl-2-me1Hylpyrrolo[l,2-b]pyridazine-3-carbonyl chloride 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 244. Example 659 7-e1Hyl-2-(me1Hoxyme1Hyl)-4-(5-me1Hyl-3-pyridinyl)pyrrolo[l,2-b]pyridazine-3-carbaldehyde 1H NMR (CDCl3) 0 1 -40 (1H, t, J= 7 Hz), 2.45 (1H, s), 3.12 (2H, q, J= 7 Hz), 3.56 (1H, s), 4.96 (2H, s), 6.51 (1H, d, J= 4 Hz), 6.80 (1H, d, J= 4 Hz), 7.62 (1H, s), 8.54 (lH,s), 8.61 (1H,S),9.79(1H,S). MS(ESl+):m/z310. ixample 660 4-(5-chloro-3-pyridinyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrrolo[l,2-b]pyridazine-3- :arbaldehyde 1H NMR (300 MHz, CDC13) 6 1.41 (1H, t, J = 7 Hz), 3.12 (2H, q, J = 7 Hz), 3.54 (1H, s), 4.94 (2H, s), 6.50 (1H, d, J = 4 Hz), 6.84 (1H, d, J = 4 Hz), 7.81 (1H, dd, J = 2,2 Hz), 8.59 (1H, d, J = 2 Hz), 8.74 (1H, d, J = 2 Hz), 9.85 (1H, s). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 533. Example 661 [7-e1Hyl-2-(me1Hoxyme1Hyl)-4-(5-me1Hyl-3-pyridinyl)pyrrolo[l,2-b]pyridazin-3-yl]me1Hanol 1H NMR (CDCl3) 5 1.38 (1H, t, J= 7 Hz), 2.43 (1H, s), 3.05 (2H, q, J= 7 Hz), 3.52 (1H, s), 4.37-4.51 (2H, br), 4.66-4.78 (2H, br), 6.20 (1H, d, J= 4 Hz), 6.67 (1H, d, J= 4 Hz), 7.75 (1H, s), 8.54 (1H, s), 8.60 (1H, s). MS(ESI+):m/z312. Example 662 [4-(5-chloro-3-pyridinyl)-7-e1Hyl-2-(nie1Hoxyme1Hyl)pyrrolo[l,2-b]pyridazin-3- yl]me1Hanol 1H NMR (300 MHz, CDCl3) 6 1.38 (1H, t, J = 7 Hz), 3.05 (2H, q, J = 7 Hz), 3.53 (1H, s), 4.41 (2H, d, J = 6 Hz), 4.77 (2H, s), 6.22 (1H, d, J = 4 Hz), 6.70 (1H, d, J = 4 Hz), 7.97 (1H, dd, J = 2, 2 Hz), 8.69-8.71 (2H, m). MS (m/z) 332 (M+l). Example 663 A mixture of 7-e1Hyl-2-(me1Hoxyme1Hyl)-4-(5-me1Hyl-3-pyridinyl)pyrrolo[l,2-b]pyridazine-3-carbaldehyde (48 mg) and e1Hyl (triphenylphosphoranylidene)acetate (56.8 mg) in 1HF (3 mL) was stirred at ambient temperature for 2 hours. After evaporation of solvent, 1He residue was purified by silica gel column chromatography eluting wi1H a mixture of hexane and AcOEt (5:1 - 2:1) to give e1Hyl (2E)-3-[7-c1Hyl-2- (me1Hoxyme1Hyl)-4-(5-me1Hyl-3-pyridinyl)pyrrolo[J,2-b]pyridazin-3-yl]aci7late as a yellow powder (30 mg). e1Hyl (2E)-3-[7-e1Hyl-2-(me1Hoxyme1Hyl)-4-(5-me1Hyl-3-pyridinyl)pyrrolo[l,2- b]pyridazin-3-yl]acrylate 1H NMR (CDC13) 6 1 -26 (1H, t, J= 7 Hz), 1.39 (1H, t, J= 7 Hz), 242 (1H, s), 3.07 (2H, q, J= 7 Hz), 3.51 (1H, s), 4.12 (2H, q, J= 7 Hz), 4.64 (2H, s), 5.97 (1H, d, J= 16 Hz), 6.24 (1H, d, J= 4 Hz), 6.70 (1H, d, J= 4 Hz), 7.55 (1H, s), 7.63 (1H, d, J= 16 Hz), 8.47 (1H, d, J= 2 Hz), 8.55 (1H, d, J= 2 Hz). MS(ESI+):m/z380. Example 664 To a mixture of e1Hyl 4-[4-(5-bromo-3-pyridinyl)-7-e1Hyl-2-(melhoxyme1Hyl)pyrrolo[l,2-b]pyridazin-3-yl]butanoate (75.0 mg), cyclopropylboronic acid (18.2 mg), tricyclohexylphosphine (4.57 mg), and potassium phosphate (104 mg) in toluene-water (1 mL-0.2 mL) was added palladium acetate (1.83 mg). 1He mixture was stirred for 2 hours at 100°C. 1He mixture was partitioned between EtOAc and water. 1He organic layer was washed wi1H brine, dried over MgS04, and evaporated. Preparative silicagel 1Hin layer chtomatography (EtOAc-hexanes = 1-3) afforded e1Hyl 4-[4-(5-cyclopropyl-3-pyridinyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrrolo[l,2-b]pyridazin-3-yl]butanoateas an yellow gum (60.9 mg). e1Hyl 4-[4-(5-cyclopropyl-3-pyridinyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrrolo[l,2-b]pyridazin-3-yl]butanoate 1H-NMR (CDCl3) 5 0.76 (2H, m), 1.07 (2H, m), 1.20 (1H, t, J= 7 Hz), 1.37 (1H, t, J = 7 Hz), 1.68 (2H, m), 1.96 (1H, m), 2.17 (2H, m), 2.56 (2H, m), 3.02 (2H, q, J = 7 Hz), 3.46 (1H, s), 4.03 (2H, q, J = 7 Hz), 4.65 (2H, m), 5.90 (1H, d, J = 5 Hz), 6.57 (1H, d, J = 5 Hz), 7.30 (1H, m), 8.40 (1H, m), 8.51 (1H, m). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 664. Example 665 e1Hyl 5-[4-(5-cyclopropyl-3-pyridiny])-7-e1Hy]-2-(me1Hoxyme1Hy])pyrrolofl,2-b]pyridazin-3-yI]pentanoate 1H-NMR (CDC13) 6 0.76 (2H, m), J .08 (2H, m), 1.23 (1H, 1J = 7 Hz), 1.35-157 (7H, m), 1.96 (1H, m), 2.16 (2H, t, J = 7 Hz), 2.53 (2H, m), 3.03 (2H, q, J = 7 Hz), 3.46(1H,s),4.08(2H,q,J = 7Hz),4.62(2H,s),5.89OH,d,J = z),656(1H, d, J = 5 Hz), 7.29 OH, m), 8.40 (1H, m), 8.52 (1H, m). Example 666 e1Hyl 3-[4-(5-cyclopropyl-3-pyridinyl)-7-e1Hyl-2-(me1Hoxyme1Hyl)pyrrolo[ 1,2- b]pyridazin-3-yl]propanoate 1H-NMR(CDCl3)5 0.76(2H,m), 1.08 (2H,m), 1.19 (1H, t, J = 7 Hz), 1.37(1H,t,J = 7 Hz), 1.97 (1H, m), 2.38 (2H, m), 2.85 (2H, m), 3.02 (2H, q, J = 7 Hz), 3.46 (1H, s), 4.04 (2H, q, J = 7 Hz), 4.64 (2H, s), 5.92 (1H, d, J = 5 Hz), 6.59 (1H, d, J = 5 Hz), 7.29 (1H, m), 8.40 (1H, m), 8.53 OH, m). Example 667 tert-butyl 3-[3-cyano-7-e1Hyl-2-(l-pyrrolidinyl)pyrrolo[l,2-b]pyridazin-4-yl]-5- cyclopropylbenzoate 1H-NMR (CDC13) 6 0.81 (2H, m), 1.03 (2H, m), 1.35 (1H, t, J = 7 Hz), 1.59 (9H, s), 1.94-2.08 (, m), 2.94 (2H, q, J = 7 Hz), 3.68-3.77 (4H, m), 6.35 (1H, j, J = 5 Hz), 6.55 OH, d, J = 5 Hz), 7.43 (1H, s), 7.84 (1H, s), 7.97 (1H, s). Example 668 A solution of tert-butyl 3-bromo-5-[3-cyano-7-e1Hyl-2-(l-pyrrolidinyl)pyrrolo[l,2-b]pyridazin-4-yl]benzoate (16.0 mg) in trifluoroacetic acid (05 mL) was stirred for 0.5 hour at room temperature. 1He reaction was quenched by adding water. 1He mixture was neutralized by adding NaOH (pH = 3). 1He mixture was extracted wi1H EtOAc. 1He extract was washed wi1H brine, dried over MgS04, and evaporated to give a greenish yellow solid. 1He solid was triturated in hexanes-CHCb (2-1) to afford 3-bromo-5-[3-cyano-7-e1Hyl-2-(l-pyrrolidinyl)pyrrolo[l,2-b]pyridazin-4-yl]benzoic acid as an yellow powder (10.8 mg). 3-bromo-5-[3-cyano-7-e1Hyl-2-(l-pyrrolidinyl)pyrrolo[l,2-b]pyridazin-4-yl]benzoic acid M-I-NMR (CDCb + CD3OD) 5 136 (1H, t, J = 7 Hz), 2.0] (4H, m), 2.94 (2H, q, J = 7 Hz), 3.72 (4H, m), 6.36 (1H, d, J - 5 Hz), 6.60 (J H, d, J = 5 Hz), 7.92 (1H, m), 8.23(lH,m),835(1H,m). 1He following compound(s) was(were) obtained in a similar manner to 1Hat of Example 668. Example 669 3-[3-cyano-7-e1Hyl-2-(l-pyrrolidinyl)pyrrolo[l,2-b]pyridazin-4-yl]-5-cyclopropylbenzoic acid 1H-NMR (CDC13 + CD3OD) 6 0.81 (2H, m), 1.05 (2H, m), 1.35 (1H, t, J = 7 Hz), 2.01 (, m), 2.94 (2H, q, J = 7 Hz), 7.73 (4H, m), 637 (1H, d, J = 5 Hz), 6.57 (1H, d, J = 5 Hz), 6.98 (1H, s), 7.90 (1H, s), 8.08 (lH,s). Example 670 3-bromo-5-[7-e1Hyl-3-(me1Hylsulfonyl)-2-(l-pyrrolidinyl)pyrrolo[l,2-b]pyridazin-4-yl]benzoic acid 1H-NMR (CDCb + CD30D) 5 137 (1H, t, J = 7 Hz), 1.98 (4H, m), 2.99 (2H, q, J = 7 Hz), 320 (1H, s), 3.56 (4H, m), 632 (1H, d, J = 5 Hz), 6.67 (1H, d, J = 5 Hz), 7.80 (1H, m), 8.08 (1H, m), 830 (1H, m). Example 671 To a 3-necked frask containing Zn-Cu couple was added a solution of e1Hyl 4-iodobutanoate (369 mg) in toluene (3 mL) and N,N-dime1Hylacetamide (0.2 mL) at ambient temperature under N2. 1He mixture was stirred at 1He temperature for 1 h and 1Hen at 601H for 3 h. A suspension of tetrakis(triphenylphosphine)palladium (44 mg) in toluene (0.5 mL) was added and stirred for 5 min. After removal of an oil ba1H, 1He mixture was cooled in an ice-water ba1H. To 1His mixture was added a solution of 4-(2-chloro-4-pyridinyl)-7-e1Hyl-2-me1Hylpyrrolo[l,2-b]pyridazine-3-carbonyl chloride (212 mg) in DCM (1 mL) dropwise. After 10 min, 1He reaction mixture was stirred at ambient temperature for 2 h. 1He reaction mixture was partitioned between AcOEt and H2O. 1He organic layer was washed wi1H sat. NCO3 and brine, dried over MgS04, and evaporated in vacuo. 1He residue was purified by flash silica gel chromatography (silica gel, 80 mL) eluled wi1H hexane-AcOEt = 10-1 and 5-1 to give e1Hyl 5-[4-(2-chloro-4- pyridiny])-7-e1Hyl-2-me1Hylpyrrolo[l,2-b]pyridazin-3-yI]-5-oxopentanoate as yellow amorphous (J43 mg). e1Hyl 5-[4-(2-ch]oro-4-pyridiny])-7-elhy]-2-me1Hy]pyrroIo[l,2-b]pyridazin-3-yl]-5-oxopenlanoate 1HNMR(CDC13)& l.23(1H,t,J = 8H2),138(1H,t,J = 8Hz),l.7l-l.84(2H,m), 2.17 (1H, t, J = 8 Hz), 2.32 (1H, t, J = 8 Hz), 2.46 (1H, s), 3.04 (2H, q, J = 8 Hz), 4.06(2H,q,J = 8Hz),6.32(1H,d,J = z),6.70(lH,d,J = 5 Hz), 7.32 (1H, dd, J = 5, 1), 7.46 (1H, br s), 8.53 (1H, d, J = 5 Hz). Example 672 To a solution of 5-[4-(2-chloro-4-pyridinyl)-7-e1Hyl-2-me1Hylpyrro]ofl,2-b]pyridazin-3-yl]-5-oxopentanoic acid (47 mg) in EtOH (1 mL) was added sodium borohydride (5 mg) in an ice-water ba1H under N2. After 10 min, 1He mixture was stirred at ambient temperature. After 1 h, ano1Her odium borohydride (5 mg) was added. After 2 h, 1He reaction mixture was partitioned between CHCl3 and H2O. 1He aqueous layer was extracted wi1H CHCl3 twice. 1He combined organic layer was dried over MgS04 and evaporated in vacuo. 1He residue was purified by p-TLC (CHCl3-MeOH = 10-1) to give 5-[4-(2-chloro-4-pyridiny])-7-e1Hy]-2-me1Hy]pyrrolo[l,2-b]pyridazin-3-yl]-5-hydroxypentanoic acid as yellow amorphous (28 mg). 5-[4-(2-chloro-4-pyridinyl)-7-e1Hyl-2-me1Hy]pyrro]o[l,2-b]pyridazin-3-yl]-5-hydroxypentanoic acid 1H NMR (CDCl3) 6 1.36 (1H, t, J = 8 Hz), 1.46-1.83 (1H, m), 1.95 (1H, m), 2.70 (1H, br s), 3.01 (2H, q, J = 8 Hz), 4.63 (1H, m), 5.85 (1H, m), 6.55 (1H, d, J = 5 Hz), 7.18-7.29 (1H, overlapped wi1H CDCl3), 7.34 (1H, d, J = 2 Hz), 8.49 (1H, d, J = 5 Hz). WE CLAIM: 1. A compound of 1He formula R7is (1) hydrogen, (2) substituted or unsubstituted aryl, (3) substituted or unsubstituted heterocyclic groups, containing 1 to 2 nitrogen atom(s) (4) carboxy, protected carboxy or CONRIORU, (5) acyl or halocarbonyl, (6) cyano, (7) amino, protected amino, or mono- or di(C1-6)alkylamino, (8) hydroxy, aryloxy, acyloxy or C1-6 alkyl optionally substituted by hydroxy or acyloxy, (9) C1-6alkyl1Hio, C1-6alkylsulfinyl or C1-6alkylsulfonyl, or (10) -O-R12, or R' and Rz are combined toge1Her to form C1-6 alkylene or C2-6 alkenylene group which is optionally interrupted by amino or sulfonyl and optionally fuse wi1H benzene ring, and also is optionally substituted by 1He group consisting of C1-6alkyl, hydroxy, oxo and C1-6alkoxy, R3 is substituted aryl, or substituted or unsubstituted heterocyclic group, R4 is hydrogen, halogen, cyano, carbamoyl, acyl, 1Hiocyanate, C1-6 alkyl1Hio, C2-6 alkenyl, hydroxyl(C1-6)alkyl, trihalo(C1-6)alkyl or C1-6 alkyl, R5, R6, R10 and R11 each independently represents hydrogen, C1-6 alkylsulfonyl, heterocyclic group or C1-6 alkyl optionally substituted by hydroxy, alkoxy, sulfo, carboxy, protected carboxy or -R or alternatively R5 and R6 or R10 and R11 toge1Her wi1H 1He nitrogen atom to which 1Hey are attached, represent N-containing heterocyclic group, and R12 and R17 are each independently a group derived from protected or unprotected sugar by removal of 1He hydroxy group 1Herefrom, or a pharmaceutical1H acceptable salt 1Hereof, or prodrug 1Hereof. 2. A compound as claimed in claim 1, wherein R1 is (1) carboxy or protected caxboxy, (2)-CONR5R6 [wherein R5 and R6 each independently represents C1-6 alkyl, or alternatively R5 and R6, toge1Her wi1H nitrogen atom to which 1Hey are attached represents saturated 5- or 6-membered heteromonocyclic group containing I to 2 nitrogen atom(s)], (3) hydroxy or C1-6alkoxy, (4) amino, cyclo(C3_7)alkylamino, or mono- or di(C1-6)alkylamino optionally substituted by C1-6 alkoxy, (5) trihalo (O3alkyl, (6)trihalo (C1-6)alkylsulfonyloxy or arylsulfonylamino, (7) C1-6 alkyl optionally substituted by (i) halogen; (ii) carboxy; (iii) protected carboxy; (iv) cyano; (v)carbamoyl; (vi) -OCONR15R16 [wherein R15 and R16 each independently represents hydrogen, aryl or C1-6 alkyl optionally substituted by aryl, or R15 and R16, toge1Her wi1H 1He nitrogen atom to which 1Hey are attached, represents saturated 5- or 6-membered heteromonocyclic group containing 1 to 2 nitrogen atom(s) and also optionally containing oxygen atom,]; (vii) C1-6 alkyltihio.; (viii) C1-6alkylsulfonyl; (ix) C1-6Halkylsulfonyloxy; (x)C1-6alkylsulfonylamino; (xi) mono- or di(C1-6)alkylamino optionally substituted by hydroxy, C1-6 alkoxy, aryloxy, or substituted or unsubstituted aryl; (xii) amino; (xiii) acylamino; (xiv) protected amino; (xv) hydroxy; (xvi) acyloxy; (xvii) cyclo(C3-7)alkyloxy; (xviii) aryloxy; (xix) aryl; (xx) saturated or unsaturated 5- or 6-meinbered heteromonocyclic group containing 1 to 3 nitrogen atom(s) and also optionally containing oxygen atom or sulfur atom which is optionally substituted by C1-6 alkyl, hydroxy1H _6)alkyl, aryl or oxo; or (xxi) C1-6 alkoxy optionally substituted by carboxy, protected carboxy, hydroxy, protected hydroxy, C]_6 alkoxy, cyclo(C3_7) alkyl, substituted or unsubstituted aryl, saturated or unsaturated 5- or 6-membered heteromonocyclic group containing 1 to 2 nitrogen atom(s) optionally substituted by C 1-6 alkyl, or -CONR13R14 [wherein R13 and R14 each independently represents hydrogen or C1-6 alkyl optionally substituted by aryl, or R13 and R14, toge1Her wi1H 1He nitrogen atom to which 1Hey are attached, represents saturated 5- or 6-membered heteromonocyclic group containing 1 to 2 nitrogen atom(s) and also optionally containing oxygen atom.], (8) aryl optionally substituted by 1He substituent(s) selected from 1He group consisting of halogen, or (9) saturated or unsaturated 5- or 6-membered heteromonocyclic group optionally substituted by C1-6 alkyl or halogen. R2isR7or-(AVX-A2-R7 wherein p is Oor 1; A1 is (CrC2)alkylene or—CH=CH-; A is —(CH2)n- or -(CH=CH)m- [wherein n is integer which may range from 1 to 6 and m is integer which may range from I to 3]; X is single bond, -0-, -NR8-, -C(=0)-, -C(=NR9)- or hydroxy(Cr C2) alkylene; [wherein R8 is hydrogen or O3 alkyl, and R9 is substituted or unsubstituted pyrrolyl] R7is (1) hydrogen (2) aryl optionally substituted by C1-6 alkoxy, (3) unsaturated heteromonocyclic group containing 1 to 2 nitrogen atom(s), (4) carboxy, esterified carboxy or -CONR10RU [wherein R10 and R1 ˚each independently represents hydrogen, Cj_6 alkylsulfonyl, unsaturated heteromonocyclic group containing 1 to 2 nitrogen atom(s) or C1-6 alkyl optionally substituted by hydroxy, alkoxy, carboxy, protected carboxy, sulfo or-R17 alternatively RI0and R11 toge1Her wi1H 1He nitrogen atom to which 1Hey are attached, represents saturated 5- or 6-membered heteromonocyclic group containing 1 to 2 nitrogen atom(s) and also optionally containing oxygen atom such as morpholinyl], (5) acyl or halocarbonyl, (6) cyano, (7)amino, protected amino or mono- or di(C1-6)alkylamino, (8)hydroxy, aryloxy, acyloxy or C1-6 alkoxy optionally substituted by hydroxy or acyloxy, (9) C1-6 alkyl1Hio, C1-6 alkylsulfinyl or C1-6 alkylsulfonyl, or (10) -OR12, or R3 is (1) aryl substituted by at least one substituent(s) selected from 1He group consisting of(i) halogen, (ii) carboxy, (iii) protected carboxy, (iv) cyano, (v) -CONR15R16 [wherein R15 and R16 each independently represents hydrogen, C1-6 alkyl optionally substituted by hydroxy], (vi) C1-6 alkyl, (vii) cyclo(C3_7)alkyl, (viii) hydroxy(C1-6)alkyl, (ix) C1-6alkoxy, (x) trihalo(C1-6)alkyl, (xi) unsaturated 5- or 6-membered heteromonocyclic group containing 1 to 2 oxygen atom(s) and 1 to 2 nitrogen atom(s), (xii) C1-6 alkylsulfonyl, (xiii) nitro, (xiv) sulfamoyl, and (xv) protected sulfamoyl; or (2) heterocyclic group selected from 1He group consisting of pyridinyl, pyrazinyl, oxazolyl, isooxazolyl, furanyl, 1Hienyl, quinolinyl, benzofuranyl and benzo1Hienyl, wherein said heterocyclic group is optionally substituted by at least one substituent(s) selected from 1He group consisting of (i) C1-6 alkyl, (ii) cyclo(C3-7)alkyl, (iii) C1-6 alkoxy, (iv) acyl, (v) amino, (vi) mono- or di(C1-6)alkylamino, (vii) protected amino, (viii) cyano, (ix) carboxy, (x) protected carboxy, (xi) -CONR15R16 [wherein R15 and R16 each independently represents hydrogen, C1-6 alkyl optionally substituted by hydroxy], (xii) C2-6alkenyl optionally substituted by C1-6 alkoxy, (xiii) halogen, (xiv) C1-6 aikyl1Hio and (xv) hydroxyl; R4 is hydrogen, halogen, cyano, carbamoyl, acyl, 1Hiocyanate, O3 aikyl1Hio, C2-6 alkenyl, hydroxyl(C1-6 )alkyl, trihalo(C1-6)alkyl or C1-6 alkyl, R12 and R17 are each independently a group derived from protected or unprotected sugar such as galactose by removal of 1He hydroxy group 1Herefrom. 3. A compound as claimed in claim 2, wherein R4 is d.6 alkyl. 4. A compound as claimed in claim 3, wherein R1 is (1) mono- or di(C1-6)alkylamino, (2) phenyl, (3) saturated or unsaturated 5 to 6 membered heteromonocyclic group selected from 1He group consisting of pyrrolidinyl, pyrrolyl, oxazolyl, isooxazoiyl, 1Hiazolyl, furanyl, 1Hienyl and pyridinyl, or (4) C1-6 alkyl optionally substituted by (i) C1-6 alkoxy or (ii) saturated 5-or 6-membered heteromonocyclic group selected from 1He group consisting of piperazinyl and morpholinyl, wherein C1-6 alkoxy is optionally substituted by cyclo(C3-7) alkyl or pyridinyl. 5. A compound as claimed in claim 4, wherein R2 is R7 or -A2-R7, wherein A is —(CH2)n- or —(CH=CH)m- [wherein n is integer which may range 2 to 6 and m is integer of 1 or 2, and R is hydrogen, C1-6 alkyl sulfonyl., carboxy, esterified carboxy or pyridinyl, R3 is (1) phenyl substituted by C1-6 alkyl, cyclo(C3-7) alkyl, C1-6 alkoxy, halogen, cyano or carbamoyl; or (2) quinolinyl; or pyridinyl substituted by C1-6 alkyl, cyclo(C3-7)alkyl, C1-6 alkoxy, carbamoyl or halogen. 6. A compound as claimed in claim 5, wherein R1 is phenyl, pyrrolyl, isooxazolyl, furanyl, 1Hienyl,C1-6 alkyl optionally substituted by C1-6 alkoxy, piperazinyl or morpholinyl, wherein O3 alkoxy is optionally substituted by cyclo(C3-7)alkyl or pyridinyl, R2 is -(CH2)n-R7,wherein n is integer which may range 2 to 5, and R7 is carboxy or esterified carboxy, and R3 is (1) phenyl substituted by O3 alkyl; cyclo(C3-7)alkyl, C1-6 alkoxy, halogen, cyano or carbamoyl; or (2) pyridinyl substituted by C1-6 alkyl, cyclo(C3-7)alkyl, C1-6 alkoxy, carbamoyl or halogen. (TNF). 12, A pharmaceutical composition of claim 10, for prevention or treatment of diseases for which 1Herapy by a PDE-IV inhibitor or TNF produxtion inhibitor is relevant, 13. A pharmaceutical composition of cJaira 10, for prevention or treatment of as1Hma, chronic obstructive pulmonary disease (CGPD), fibrotic disease, acute and fulminant hepatitis, hepatic steatosis (alcoholic or non-alcoholic steatohepatitis), chronic (viral or non-viral) hepatitis, hepatic cinhosis, autoimmune hepatitis, autoimmune inflammatory bowel disease, atopic dermatitis, Alzheimer's diseases and viral infection.

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1516-chenp-2005-abstract.pdf

1516-chenp-2005-claims.pdf

1516-chenp-2005-correspondnece-others.pdf

1516-chenp-2005-correspondnece-po.pdf

1516-chenp-2005-description(complete).pdf

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1516-chenp-2005-form 18.pdf

1516-chenp-2005-form 26.pdf

1516-chenp-2005-form 3.pdf

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