Title of Invention	PYRAZOLE DERIVATIVES USEFUL AS COX-I INHIBITORS
Abstract	A compound of the formula (I): wherein R<sup>1</sup> is hydrogen or lower alkyl; R<sup>2</sup> is lower alkyl, etc.; R<sup>3</sup> is lower alkoxy, etc.; R<sup>4</sup> is hydroxy, etc.; X is 0, S, etc.; Y is CH or N; Z is lower alkylene or lower alkenylene; anc m is 0 or 1; or salts thereof, which are useful as a medicament.

Full Text

Technical Field This invention relates to pyrazole compounds having pharmacological activity, to a process for their production and to a pharmaceutical composition containing the same. Background Art The presence of two cyclooxygenase isoenzymes, cyclooxygenase-I (COX-I) and cyclooxygenase-II (COX-II) is known (Proc. Nat. Acad. Sci. USA 88, 2692-2696 (1991)). Traditional non steroidal anti-inflammatory compounds (NSAIDs) have inhibiting activities of both COX-I and COX-II (J. Biol. Chem., 268, 6610-6614 (1993), etc). The therapeutic use thereof involves undesired effects on the gastrointestinal tract, such as bleeding, erosions, gastric and intestinal ulcers, etc. It was reported that selective inhibition of COX-II shows anti-inflammatory and analgesic activities comparable with conventional NSAIDs but with a lower incidence of some gastrointestinal undesired effects (Pro. Nat. Acad. Sci. USA, 91, 3228-3232(1994)). Accordingly, various selective COX-II inhibitors have been prepared. However, it was reported that those "selective COX-II inhibitor" show some side-effects on kidney and/or insufficient efficacy on acute pains. Further, some compounds such as SC-560, mofezolac, etc, which have certain selective inhibiting activity against COX-I. WO98/57910 shows some compounds having such activity. However, their selectivity of inhibiting COX -I does not seem to be enough to use them as a clinically acceptable and satisfactory analgesic agent due to their gastrointestinal disorders. WO02/055502 shows some pyridine derivatives having cyclooxygenase inhibiting activity, particularly cyclooxygenase-I inhibiting activity. Further, WO03/040110 shows some triazole derivatives having cyclooxygenase inhibiting activity, particularly cyclooxygenase-I inhibiting activity. And WO99/51580 shows some triazole derivatives having an inhibiting activity of cytokine production. Disclosure of Invention This invention relates to pyrazole compounds, which have pharmacological activity such as cyclooxygenase (hereinafter described as COX) inhibiting activity, to a process for their production, to a pharmaceutical composition containing the same and to a use thereof. Accordingly, one object of this invention is to provide the pyrazole compounds, which have a COX inhibiting activity. Another object of this invention is to provide a process for production of the pyrazole compounds. A further object of this invention is to provide a pharmaceutical composition containing, as active ingredients, the pyrazole compounds. Still further object of this invention is to provide a use of the pyrazole compounds for manufacturing a medicament for treating or preventing various diseases. The new pyrazole compounds of this invention can be represented by the following general formula (I): wherein R1 is hydrogen or lower alkyl; R2 is lower alkyl optionally substituted with halogen, hydroxy, lower alkoxyimino or lower alkoxy; lower alkenyl; cycloalkyl; cyano; lower alkanoyl; cycloalkylcarbonyl; N,N-di(lower)alkylcarbamoyl; carbamoyl; N-lower alkoxy-N-lower alkylcarbamoyl; amino; di (lower)alkylamino; lower alkoxycarbonylamino; N,N-di(lower)alkylcarbamoylamino; N-(N,N-di(lower)alkylcarbamoyl)-N-lower alkylamino; halogen; hydroxy; carboxy; lower alkoxycarbonyl; aroyl; heterocycliccarbonyl; heterocyclic group; lower alkylsulfonyl; lower alkoxy optionally substituted with lower alkoxy, N,N-di(lower)alkylcarbamoyl or halogen; cycloalkyloxy; lower alkylthio; or lower alkylsufinyl; R3 is lower alkyl optionally substituted with amino, carbamoylamino or lower alkylsulfonylamino; halogen; cyano; hydroxy; lower alkanoyloxy; lower alkylenedioxy; lower alkoxy optionally substituted with aryl, hydroxy, cyano, amino, lower alkoxycarbonylamino, lower alkylsulfonylamino or carbamoylamino; nitro; amino; hetrocyclic group; lower alkylthio; lower alkylsulfinyl; or lower alkylsufonyl; R4 is hydrogen; cyano; amino optionally substituted with phthaloyl or lower alkyl; aryl; heterocyclic group; lower alkoxy; hydroxy; lower alkylsulfonyloxy; lower alkanoyloxy; lower alkyl substituted with tritylamino and lower alkoxycarbonyl, amino and lower alkoxycarbonyl, amino and carboxy, amino and carbamoyl, or amino and hydroxy; N-lower alkoxycarbonyl-N-lower alkylamino; lower alkanoyl optionally substituted with halogen; carboxy; lower alkylsulfonyl; sulfo; lower alkylsilyloxy; lower alkoxycarbonyl; sulfamoyl optionally substituted with lower alkyl; carbamoyl optionally substituted with lower alkyl; lower alkylthio; lower alkylsulfinyl; carbamoyloxy; thioureido; or a group of the formula: R5-G-J-in which G is -CO- or -S02-; J is -N(R6)-(wherein R6 is hydrogen or lower alkyl); and R5 is amino optionally substituted with lower alkoxycarbonyl or lower alkyl; lower alkyl optionally substituted with hydroxy, lower alkoxycarbonylamino, lower alkanoyloxy, amino or halogen; lower alkoxy; hydrogen; heterocyclic group; or aryl; X is 0, S, SO or S02; Y is CH or N; Z is lower alkylene or lower alkenylene; and m is 0 or 1; provided that when R4 is hydrogen; then R3 is lower alkyl substituted with amino, carbamoylamino or lower alkylsulfonylamino; or lower alkoxy substituted with aryl, hydroxy, cyano, amino, lower alkoxycarbonylamino, lower alkylsulfonylamino or carbamoylamino; or salts thereof. The object compound (I) of the present invention can be prepared by the following processes. Process (1) In the above processes, R1, R2, R3, R4, X, Y, Z and m are each as defined above, Xa is 0 or S, and Q is hyroxy or an acid residue. The compounds of formula (I) may contain one or more asymmetric centers and thus they can exist as enantiomers or diastereoisomers. This invention includes both mixtures and separate individual isomers. The compounds of the formula (I) may also exist in tautomeric forms and the invention includes both mixtures and separate individual tautomers. The compounds of the formula (I) and its salts can be in a form of a solvate, which is included within the scope of the present invention. The solvate preferably include a hydrate and an ethanolate. Also included in the scope of invention are radiolabelled derivatives of compounds of formula (I) which are suitable for biological studies. In the above and subsequent description of the present specification, suitable examples of the various definitions to be included within the scope of the invention are explained in detail in the following. The term "lower" is intended to mean a group having 1 to 6 carbon atom(s), unless otherwise provided. So, the "lower alkyl" and lower alkyl moiety in the terms "lower alkylthio", "lower aklylsufinyl", "lower alkylsulfonyl" and "lower alkylsulfonylamino" means a straight or branched chain aliphatic hydrocarbon, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, isoamyl, hexyl, and the like, and it is preferably (C1-C4) alkyl, more preferably (Ci-C2) alkyl, most preferably methyl. The "halogen" may include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and it is preferably a fluorine atom or a chlorine atom, more preferably a chlorine atom. The "lower alkyl substituted with halogen" means a monovalent group in which the above lower alkyl is substituted by one or more (more preferably 1 to 5, most preferably 1 to 3) above halogen atom(s), such as fluoromethyl, chloromethyl, difluoromethyl, dichloro- methyl, dibromomethyl, trifluoromethyl, trichloromethyl, fluoroethyl, chloroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 2,2,3,3,3-pentafluoroethyl, fluoropropyl, fluorobutyl, fluorbhexyl, or the like, and it is preferably (C1-C4) alkyl substituted with halogen, more preferably (Cx-C2) alkyl substituted with halogen, more preferably (Ci-C2)alkyl substituted with fluorine, more preferably methyl substituted with fluorine, most preferably difluoromethyl or trifluoromethyl. The "lower alkyl substituted with hydroxy" means a monovalent group in which the above lower alkyl is substituted by a OH group, such as hydroxymethyl, hydroxyethyl, hydroxypropyl, 1-hydroxyisopropyl, 2-hydroxyisopropyl, hydroxybutyl, hydroxyisobutyl, hydroxy-tert-butyl, hydroxyhexyl, or the like, and it is preferably (Ci-C4)alkyl substituted with hydroxy, more preferably (C1-C3)alkyl substituted with hydroxy. The "lower alkenyl" means a straight or branched chain aliphatic hydrocarbon having more than one double bond between two carbon atom, such as ethenyl, propenyl, isopropenyl, butenyl, isobutenyl, pentenyl, hexenyl, and the like, and it is preferably (C2-C4) alkenyl, more preferably (C2-C3) alkenyl. The "lower alkoxy" means a straight or branched chain aliphatic hydrocarbon oxy group, such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, pentoxy, hexoxy, or the like, and it is preferably (C1-C4) alkoxy, more preferably (C1-C2) alkoxy, most preferably methoxy. The "cycloalkyl" and cycloalky moiety in the terms "cycloalkylcarbonyl" and "cycloalkyloxy" means C3-C10 cycloalkyl group, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, norbornyl, adamantyl, and the like, and it is preferably C3-C6 cycloalkyl, more preferably C3-C5 cycloalkyl, most preferably cyclopropyl or cyclopentyl. The "di(lower)alkylamino" means a amino group substituted by the same or different above (lower)alkyl groups, such as dimethylamino, diethylamino, dipropylamino, diisopropylamino, dibutylamino, diisobutylamino, dipentylamino, dihexylamino, ethylmethylamino, methylpropylamino, butylmethylamino, ethylpropylamino, butylethylamino, or the like, and it is preferably ■ [di(C1-C4)alkyl]amino, more preferably [di(C1-C4)alkyl]amino, most preferably dimethylamino. The "lower alkoxycarbonyl" and lower alkoxycarbonyl moiety in the term "lower alkoxycarbonylamino" means a -C02-[(lower)alkyl] group, such as methoxycarbonyl, ethoxycarbonyl, propoxycafbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, pentoxycarbonyl, hexoxycarbonyl, and the like, and it is preferably [(C1-C4)alkoxy]carbonyl, more preferably ethoxycarbonyl or tert-butoxycarbonyl- The "lower alkanoyl" means carbonyl group which is substituted by hydrogen or the above (lower)alkyl groups, such as formyl, acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 2,2-dimethylpropanoyl, hexanoyl, or the like, and it is preferably (C1-C5) alkanoyl, more preferably (C2-C3) alkanoyl, most preferably acetyl. The "cycloalkylcarbonyl" means a carbonyl group substituted with cycloalkyl group mentioned above, such as cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, norbornylcarbonyl, adamantylcarbonyl, and the like, and it is preferably [ (C3~C6)cycloalkyl]carbonyl, more preferably [ (C3-C5)cycloalkyl]carbonyl, most preferably cyclopropylcarbonyl. The "N,N-di(lower)alkylcarbamoyl" and N,N-di(lower)alkylcarbamoyl moiety in the term "N,N-di(lower)alkylcarbamoylamino" means a carbamonyl group substituted with the same or different lower alkyl groups mentioned above, such as dimethylcarbamoyl, diethylcarbamoyl, dipropylcarbamoyl, diisopropylcarbamoyl, dibutylcarbamoyl, diisobutylcarbamoyl, dipentylcarbamoyl, dihexylcarbamoyl, ethylmethylcarbamoyl, methylpropylcarbamoyl, butylmethylcarbamoyl, ethylpropylcarbamoyl, butylethylcarbamoyl, and the like, and it is preferably [di(C1-C4)alkyl]carbamoyl, more preferably [di(C1-C2)alkyl]carbamoyl, most preferably dimethycarbamoyl or ethylmethylcarbamoyl. The "lower alkoxy substituted with halogen" means a monovalent group in which the above lower alkoxy is substituted by one or more (more preferably 1 to 5, most preferably 1 to 3) above halogen atom(s), such as fluoromethoxy, chloromethoxy, difluoromethoxy, dichloromethoxy, dibromomethoxy, trifluoromethoxy, trichloromethoxy, fluoroethoxy, chloroethoxy, 2,2-difluoroethoxy, 2,2-dichloroethoxy, 2,2,2-trifluoroethoxy, 2,2,2-trichloroethoxy, 2,2,3,3,3-pentafluoroethoxy, fluoropropoxy, fluorobutoxy, fluorohexyloxy, or the like, and it is preferably (C1-C4)alkoxy substituted with halogen, more preferably (C1-C2)alkoxy substituted with halogen, more preferably (C1-C2)alkoxy substituted with fluorine, more preferably ethoxy substituted with fluorine, most preferably 2,2-difluoroethoxy. The "lower alkyl substituted with amino" means a monovalent group in which the above lower alkyl is substituted by a amino group, such as aminomethyl, 2-aminoethyl, aminopropyl, 1-aminoisopropyl, 2-aminoisopropyl, aminobutyl, aminoisobutyl, amino-tert-butyl, aminohexyl, or the like, and it is preferably (C1-C4)alkyl substituted with amino, more preferably (Ci-C2)alkyl substituted with amino. The "lower alkyl substituted with carbamoylamino" means a monovalent group in which the above (lower)alkyl is substituted by a carbamoylamino group (urea group) , such as carbamoylaminomethyl, 2-(carbamoylamino)ethyl, carbamoylaminopropyl, 1-(carbamoylamino)isopropyl, 2-(carbamoylamino)isopropyl, carbamoylaminobutyl, carbamoylaminoisobutyl, carbamoylamino-tert-butyl, carbamoylaminohexyl, or the like, and it is preferably (C1-C4)alkyl substituted with carbamoylamino, more preferably (Ci-C2)alkyl substituted with carbamoylamino. The "aryl" and ar moiety in the term "aroyl" means an aromatic hydrocarbon group, such as phenyl, naphtyl, indenyl, or the like, and it is preferably (C6-Cio) aryl, more preferably phenyl. The "aroyl" means a carbonyl group substituted with aryl group mentioned above, such as benzoyl, naphthoyl, or the like, and it is preferably benzoyol. The "lower alkanoyloxy" means a monovalent group in which oxygen atom is substituted with lower alkanoyl group mentioned above, such as formyl, acetyl, propanoyl, butanoyl, 2-methylpropanoyl, pentanoyl, 2,2-dimethylpropanoyl, hexanoyl, or the like, and it is preferably [(C1-C4)alkanoyl]oxy, more preferably [ (C1-C2) alkanoyl]oxy, most preferably acetoxy. The "lower alkylene" means a straight or branched chain aliphatic hydrocarbon divalent group, such as methylene, ethylene, 1-methylethylene, 2-methylethylene, propylene, methylpropylene, butylene, pentylene, hexylene, and the like, and it is preferably (C1-C4) alkylene, more preferably (C1-C2) alkylene. The "lower alkylenedioxy" means -0-[(lower)alkylene]-0- group. That is, in this case, R3 is divalent group and is also substituted at the next carbon atom. This group may be exemplified by methylenedioxy, ethylenedioxy, methylethylenedioxy, propylenedioxy, and the like, and it is preferably [ (C1-C4) alkylene] dioxy, more preferably [ (Ci-C2) alkylene] dioxy, most preferably methylenedioxy. The "lower alkoxy substituted with aryl" means a monovalent group in which the above lower alkoxy is substituted by aryl group mentioned above. The "lower alkoxy substituted with hydroxy" means a monovalent group in which the above lower alkoxy is substituted by hydroxy. The "lower alkoxy substituted with cyano" means a monovalent group in which the above (lower)alkoxy is substituted by a cyano group, such as cyanomethoxy, cyanoethoxy, cyanopropoxy, cyanobutoxy, and the like, and it is preferably (C1-C4) alkoxy substituted with cyano, more preferably (C1-C2)alkoxy substituted with cyano, most preferably cyanomethoxy. The "lower alkoxy substituted with amino" means a monovalent group in which the above lower alkoxy is substituted with amino. The "lower alkoxy substituted with lower alkoxycarbonylamino means a lower alkoxy substituted with amino group mentioned above substituted with lower alkoxycarbonyl group mentioned above. The "lower alkoxy substituted with lower alkylsulfonylamino means a monovalent group in which the above lower alkoxy is substituted with lower alkylsulfonylamino group mentioned above. The "lower alkoxy substituted with carbamoylamino" means a monovalent group in which the above lower alkoxy is substituted by a (carbamoyl) amino (urea) group, such as [(carbamoyl)amino]methoxy, [(carbamoyl)amino]ethoxy, [(carbamoyl)amino]propoxy, [(carbamoyl)amino]cyanobutoxy, and the like, and it is preferably (C1-C4)alkoxy substituted with [(carbamoyl)amino], more preferably (Ci~C2)alkoxy substituted with [(carbamoyl)amino], most preferably carbamoylaminomethoxy. The "lower alkokycarbonylamino" means an amino group substituted with lower alkokycarbonyl group mentioned above. The "lower alkylsulfonylamino means a sulfonylamino group substituted with lower alkyl group mentioned above. Suitable "heterocyclic group" may be one containing at least one hetero atom selected from nitrogen, sulfur and oxygen atom, and may include saturated or unsaturated, monocyclic or polycyclic heterocyclic group, and preferable heterocyclic group may be N-containing heterocyclic group such as unsaturated 3 to 6-membered heteromonocyclic group containing 1 to 4 nitrogen atoms, for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazolyl [e.g. 4H-l,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc.], tetrazolyl [e.g. lH-tetrazolyl, 2H-tetrazolyl, etc.], etc.; saturated 3 to 7-membered heteromonocyclic group containing 1 to. 4 nitrogen atoms [e.g. pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl, homopiperazinyl, etc.]; unsaturated condensed heterocyclic group containing 1 to 5 nitrogen atoms, for example, indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, imidazopyridyl, indazolyl, benzotriazolyl, tetrazolopyridazinyl [e.g. tetrazolo[1,5-b]pyridazinyl, etc.], quioxalinyl, etc.; unsaturated 3 to 6-membered heteromonocyclic group containing an oxygen atom, for example, pyranyl, furyl, etc. ; saturated 3 to 6-membered heteromonocyclic group containing an oxygen atom, for example, lH-tetrahydropyranyl, tetrahydrofuranyl, etc.; unsaturated 3 to 6-membered heteromonocyclic group containing 1 to 2 sulfur atoms, for example, thienyl, etc.; unsaturated 3 to 6-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, for example, oxazolyl, isoxazolyl, oxadiazolyl [e.g. 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, etc.], oxazolinyl [e.g. 2-oxazolinyl, etc.], etc.; saturated 3 to 6-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [e.g. morpholinyl, etc.]; unsaturated condensed heterocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [e.g. benzofurazanyl, benzoxazolyl, benzoxadiazolyl, etc.]; unsaturated 3 to 6-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, for example, thiazolyl, thiadiazolyl [e.g. 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, etc.], etc.; saturated 3 to 6-membered heteromonocyclic group containing '1 to 2 sulfur atoms and 1 to 3 nitrogen atoms [e.g. thiazolidinyl, etc.]; unsaturated condensed heterocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms [e.g. benzothiazolyl, benzothiadiazolyl, etc.]; unsaturated condensed heterocyclic group containing 1 to 2 oxygen atoms [e.g. benzofurany1, benzodioxolyl, chromanyl, etc.] and the like. Said "heterocyclic group" may be substituted with lower alkyl as exemplified above or oxo, in which preferable one is pieridyl, pyrrolyl , 3-metyl-l,2,4-oxadiazol-5-yl, isoindole-1,3-dione-2-yl or 1-methyl-lH-imidazolyl. The heterocyclic moiety in the term "heterocycliccarbonyl" means heterocyclic group mentioned above and, it is preferably piperidyl. The "lower alkylsulfonyloxy" means a sulfonyloxy group substituted with lower alkyl group mentioned above. The "lower alkanoyl substituted with halogen" means a lower alkanoyl group mentioned above substituted with halogen mentioned above, such as trifluoroacetyl, and the like. The "lower alkylsilyloxy" means silyloxy group substituted by the same or different above (lower)alkyl groups, such as trimethylsilyloxy, triethylsilyloxy, tert-butyldimethylsilyloxy, or the like, and it is preferably tert-butyldimethylsilyloxy. The "acid residue" means halogen (e.g. fluoro, chloro, bromo, iodo), arenesulfonyloxy (e.g. benzenesulfonyloxy, tosyloxy, etc.), alkanesulfonyloxy (e.g. mesyloxy, ethanesulfonyloxy, etc.), and the like. Preferred compound (I) is one having hydrogen for R1; lower alkyl optionally substituted with halogen; cycloalkyl; halogen; or lower alkoxy optionally substituted with halogen for R2; 1 ower alkoxy for R ; R5-G-J-(wherein -CO- or -S02- for G, -NH- for J, amino or lower alkyl for R5) for R4; 0 for X; CH or N for Y; lower alkylene for Z; and 0 or 1 for m. Suitable salts of the compounds (I) are pharmaceutically acceptable conventional non-toxic salts and include a metal salt such as an alkali metal salt (e.g., sodium salt, potassium salt, etc.) and an alkaline earth metal salt (e.g., calcium salt, magnesium salt, etc.), an ammonium salt, an organic base salt (e.g., trimethylamine salt, triethylamine salt, pyridine salt, picoline salt, dicyclohexylamine salt, etc.), an organic acid salt (e.g., acetate, maleate, tartrate, methanesulfonate, benzenesulfonate, formate, toluenesulfonate, trifluoroacetate, etc.), an inorganic acid salt (e.g., hydrochloride, hydrobromide, sulfate, phosphate, etc.), a salt with an amino acid (e.g., arginine, aspartic acid, glutamic acid, etc.), or the like. The processes for preparing the object compounds are explained in detail in the following. Process (1) The Object compound (la) or its salt can be prepared by reacting a compound (II) or its salt with a compound (III) or its salt in the acidic condition, for example, by using acetic acid. Suitable salts of the compounds (la) and (III) may be the same as those exemplified for the compound (I). Suitable salt of the compound (II) maybe acid addition salt exemplified for the compound (I). The reaction is carried out in a conventional solvent such as water, an alcohol (e.g. methanol, ethanol, propanol, isopropanol, etc.), tetrahydrofuran, dioxane, etc. or a mixture of thereof. The reaction temperature is not critical and the reaction is usually carried out under cooling to heating. According to the starting material, the heterocyclic ring is formed but not to form pyrazole ring. In this case, the dehydration process is need to form pyrazole ring. The hydration process is carried out under the higher temperature. Process (2) The object compound (lb) or its salt can be prepared by reacting a compound (IV) or its salt with a compound (V) or its salt. Suitable salts of the compounds (la), (IV) and (V) may be the same as those exemplified for the compound (I). When the compound (V) having halogen for Q is used in this reaction, the reaction is preferably carried out in the presence of a base such as alkali metal (e.g. sodium, potassium, etc. ) , an alkaline earth metal (e.g. magnesium, calcium, etc. ), the hydride or hydroxide or carbonate or bicarbonate thereof. When the compound (V) having hydroxy for Q is used in this reaction, the reaction is preferably carried out in the presence of diethyl azodicarboxylate and triphenylphosphine. The reaction is usually carried out in a conventional solvent which does not adversely influence the reaction such as water, dioxane, a alcohol (e.g. methanol, ethanol, etc.), acetonitrile, tetrahydrofuran, acetic acid, N,N-dimethylformamide, or a mixture thereof. The reaction temperature is not critical and the reaction can be carried out under cooling to heating. In order to illustrate the usefulness of the object compounds (I), the pharmacological test data of the com pounds (I) are shown in the following. [A] ANALGESIC ACTIVITY : Effect on adjuvant arthritis in rats : (i) Test Method : Analgesic activity of a single dose of agents in arthritic rats was studied. Arthritis was induced by injection of 0.5 mg of Mycobacterium tuberculosis (Difco Laboratories, Detroit, Mich.) in 50ill of liquid paraffin into the right hind footpad of Lewis rats aged 7 weeks. Arthritic rats were randomized and grouped (n=10) for drug treatment based on pain threshold of left hind paws and body weight on day 22. Drugs (Test compounds) were administered and the pain threshold was measured 2hrs after drug administration. The intensity of hyperalgesia was assessed by the method of Randall - Selitto. The mechanical pain threshold of the left hind paw (uninjected hind paw) was determined by compressing the ankle joint with a balance pressure apparatus (Ugo Basile Co.Ltd., Varese, Italy). The threshold pressure of rats squeaking or struggling was expressed in grams. The threshold pressure of rats treated with drugs was compared with that of non-treated rats. A dose showing the ratio of 1.5 is considered to be the effective dose. [B] Inhibiting activity against COX-I and COX-II (Whole Blood Assay): (i) Test Method : Whole blood assay for COX-I Fresh blood was collected by syringe without anticoagulants from volunteers with consent. The subjects had no apparent inflammatory conditions and had not taken any medication for at least 7 days prior to blood collection. 500^1 Aliquots of human whole blood were immediately incubated with 2/il of either dimethyl sulfoxide vehicle or a test compound at final concentrations for lhr at 37°C to allow the blood to clot. Appropriate treatments (no incubation) were used as blanks. At the end of the incubation, 5/il of 250mM Indomethacin was added to stop the reaction. The blood was centrifuged at 6000 x g for 5min at 4*C to obtain serum. A 100£6l aliquot of serum was mixed with 400/xl methanol for protein precipitation. The supernatant was obtained by centrifuging at 6000 x g for 5min at 4°C and was assayed for TXB2 using an enzyme immunoassay kit according to the manufacturer' s procedure. For a test compound, the results were expressed as percent inhibition of thromboxane B2(TXB2) production relative to control incubations containing dimethyl sulfoxide vehicle. The data were analyzed by that a test compound at the indicated concentrations was changed log value and was applied simple linear regression. IC50 value was calculated by least squares method. Whole blood assay for COX-II Fresh blood was collected in heparinized tubes by syringe from volunteers with consent. The subjects had no apparent inflammatory conditions and had not taken any medication for at least 7 days prior to blood collection. 500£il aliquots of human whole blood were incubated with either 2/xl dimethyl sulfoxide vehicle or 2All of a test compound at final concentrations for 15 min at 37*0. This was followed by incubation of the blood with 10/xl of 5mg/ml lipopolysaccharide for 24hrs at 37°C for induction of COX-II. Appropriate PBS treatments (no LPS) were used as blanks. At the end of the incubation, the blood was centrifuged at 6000Xg for 5 min at 4°C to obtain plasma. A 100/i 1 aliquot of plasma was mixed with 400Atl methanol for protein precipitation. The supernatant was obtained by centrifuging at 6000Xg for 5min at 4°C and was assayed for prostaglandin E2 (PGE2) using a radioimmunoassay kit after conversion of PGE2 to its methyl oximate derivative according to the manufacturer's procedure. For a test compound, the results were expressed as percent inhibition of PGE2 production relative to control incubations containing dimethyl sulfoxide vehicle. The data were analyzed by that a test compound at the indicated concentrations was changed log value and was applied simple linear regression. IC50 value was calculated by least squares method. It appeared, from the above-mentioned Test Results, that the compound (I) or pharmaceutically acceptable salts thereof of the present invention have an inhibiting activity against COX, particularly a selective inhibiting activity against COX-I. [C] Inhibiting activity on aggregation of platelet (i) Methods Preparation of platelet-rich plasma Blood from healthy human volunteers was collected into plastic vessels containing 3.8% sodium citrate (1/10 volume). The subject had no taken any compounds for at least 7days prior to blood collection. Platelet-rich plasma was obtained from the supernatant fraction of blood after centrifugation at 1200rpm. for lOmin. Platelet-poor plasma was obtained by centrifugation of the remaining blood at 3000rpm for lOmin. Measurement of platelet aggregation Platelet aggregation was measured according to the turbidimetric method with an aggregometer (Hema Tracer)'. In the cuvette, platelet-rich plasma was pre-incubated for 2min at 37*C after the addition of compounds or vehicle. In order to quantify the inhibitory effects of each compound, the maximum increase in light transmission was determined from the aggregation curve for 7min after the addition of agonist. We used collagen as agonist of platelet aggregation in this study. The final concentration of collagen was 0.5]ig/mL. The effect of each compound was expressed as percentage inhibition agonist-induced platelet aggregation compared with vehicle treatment. Data are presented as the mean ± S .E.M. for six experiments. The IC50 value was obtained by linear regression, and is expressed as the compound concentration required to produce 50% inhibition of agonist-induced platelet aggregation in comparison to vehicle treatment. It appeared, from the above-mentioned Test Result, that the compound (I) or pharmaceutically acceptable salts thereof of the present invention have an inhibiting activity against platelet aggregation. Therefore, the compound (I) or pharmaceutically acceptable salts thereof are useful for preventing or treating disorders induced by platelet aggregation, such as thrombosis. Additionally, it was further confirmed that the compounds (I) of the present invention lack undesired side-effects of non-selective NSAIDs, such as gastrointestinal disorders, bleeding, renal toxicity, cardiovascular affection, etc. As shown above, the object compound (I) or pharmaceutically acceptable salts thereof of this invention possesses COX inhibiting activity and possesses strong anti-inflammatory, antipyretic, analgesic, antithrombotic, anti-cancer activities, and so on. The object compound (I) and pharmaceutically acceptable salt thereof, therefore, are useful for treating and/or preventing COX mediated diseases, inflammatory conditions, various pains, collagen diseases, autoimmune diseases, various immunological diseases, thrombosis, cancer and neurodegenerative diseases in human beings or animals by using administered systemically or topically-More particularly, the object compound (I) and pharmaceutically acceptable salts thereof are useful for treating and/or preventing inflammation and acute or chronic pain in joint and muscle [e.g. rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis, gouty arthritis, juvenile arthritis, scapulohumeral periarthritis, cervical syndrome, etc.]; lumbago; inflammatory skin condition [e.g. sunburn, burns, eczema, dermatitis, etc.]; inflammatory eye condition [e.g. conjunctivitis, etc.]; lung disorder in which inflammation is involved [e.g. asthma, bronchitis, pigeon fancier's disease, farmer's lung, etc.]; condition of the gastrointestinal tract associated with inflammation [e.g. aphthous ulcer, Chrohn's disease, atopic gastritis, gastritis varioloid, ulcerative colitis, coeliac disease, regional ileitis, irritable bowel syndrome, etc. ] ; gingivitis; menorrhalgia; inflammation, pain and tumescence after operation or injury [pain after odontectomy, etc.] ; pyrexia, pain and other conditions associated with inflammation, particularly those in which lipoxygenase and cyclooxygenase products are a factor, systemic lupus erythematosus, scleroderma, polymyositis, tendinitis, bursitis, periarteritis nodose, rheumatic fever, Sjogren's syndrome, Behcet disease, thyroiditis, type I diabetes, nephrotic syndrome, aplastic anemia, myasthenia gravis, uveitis contact dermatitis, psoriasis, Kawasaki disease, sarcoidosis, Hodgkin1s disease, Alzheimers disease, or the like. Additionally, the object compound (I) or a salt thereof is expected to be useful as therapeutical and/or preventive agents for cardiovascular or cerebrovascular diseases, the diseases caused by hyperglycemia and hyperlipemia. The object compound (I) and a salt thereof can be used for prophylactic and therapeutic treatment of arterial thrombosis, arterial sclerosis, ischemic heart diseases [e.g. angina pectoris (e.g. stable angina pectoris, unstable angina pectoris including imminent infarction, etc.), myocardial infarction (e.g. acute myocardial infarction, etc.), coronary thrombosis, etc.], ischemic brain diseases [e.g. cerebral infarction (e.g. acute cerebral thrombosis, etc.), cerebral thrombosis (e.g. cerebral embolism, etc.), transient cerebral ischemia (e.g. transient ischemic attack, etc.), cerebrovascular spasm after cerebral hemorrhage (e.g. cerebrovascular spasm after subarachnoid hemorrhage, etc.), etc.], pulmonary vascular diseases (e.g. pulmonary thrombosis, pulmonary embolism etc.), peripheral circulatory disorder [e.g. arteriosclerosis obliterans, thromboangiitis obliterans (i.e. Buerger's disease), Raynaud's disease, complication of diabetes mellitus (e.g. diabetic angiopathy, diabetic neuropathy, etc.), phiebothrombosis (e.g. deep vein thrombosis, etc.), etc.], complication of tumors (e.g. compression thrombosis), abortion [e.g. placental thrombosis, etc.], restenosis and reocclusion [e.g. restenosis and/or reocclusion after percutaneous transluminal coronary angioplasty (PTCA), restenosis and reocclusion after the administration of thrombolytic drug (e.g. tissue plasminogen activator (TPA), etc.)], thrombus formation in case of vascular surgery, valve replacement, extracorporeal circulation [e.g. surgery (e.g. open heart surgery, pump-oxygenator, etc.) hemodialysis, etc.] or transplantation, disseminated intravascular coagulation (DIG), thrombotic thrombocytopenia, essential thrombocytosis, inflammation (e.g. nephritis, etc.), immune diseases, atrophic thrombosis, creeping thrombosis, dilation thrombosis, jumping thrombosis, mural thrombosis, etc. . The object compound (I) and a salt thereof can be used for the adjuvant therapy with thrombolytic drug (e.g. TPA, etc.) or anticoagulant (e.g. heparin, etc.). And, the compound (I) is also useful for inhibition of thrombosis during extra corporeal circulation such as dialysis. Particularly, the following diseases are exemplified: pains caused by or associated with rheumatoid arthritis, osteoarthritis, lumbar rheumatism, rheumatoid spondylitis, gouty arthritis, juvenile arthritis, etc; lumbago; cervico-omo-brachial syndrome; scapulohumeral periarthritis; pain and tumescence after operation or injury; etc.. And on the commercial package comprising the pharmaceutical composition mentioned above, the matter, which states above mentioned effects, may be written. For therapeutic purpose, the compound (I) and a pharmaceutically acceptable salt thereof of the present invention can be used in a form of pharmaceutical preparation containing said compounds as an active ingredient, in admixture with a pharmaceutically acceptable carrier such as an organic or inorganic solid or liquid excipient suitable for oral, parenteral or external administration. The pharmaceutical preparations may be capsules, tablets, dragees, granules, inhalant, suppositories, solution, lotion, suspension, emulsion, ointment, gel, cream, or the like. If desired, there may be included in these preparations, auxiliary substances, stabilizing agents, wetting or emulsifying agents, buffers and other commonly used additives. For therapeutic purpose, the analgesic agent of the present invention can be used in a form of pharmaceutical preparation suitable for oral, parenteral or external administration. The pharmaceutical preparations may be. capsules, tablets, dragees, granules, inhalant, suppositories, solution, lotion, suspension, emulsion, ointment, gel, or the like. Particularly, the analgesic agent of this invention is useful for treating or preventing acute or chronic pains associated with acute or chronic inflammations in human beings or animals by using administered systemicall'y or topically. 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 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 (I) 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 the above and subsequent description of the present specification, the following abbreviations and acronyms mean ones as shown in the following table. The following Examples and Preparations are given only for the purpose of illustrating the present invention in more detail. Example 1-1 (IE)-1-[4-(Methoxymethoxy)phenyl]-4-methyl-l-penten-3- one 1M Sodium hydroxide aqueous solution (5.4ml) was added to a solution of 4-mehoxymethoxybenzaldehyde (4.52g) and 3-methyl-2-butanone (4.69g) in ethanol (27ml), and the mixture was stirred at room temperature overnight. The mixture partitioned between ethyl acetate and water. The organic layer was washed with water, saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel chromatography eluted with 10% ethyl acetate/n-hexane to give the title compound (4.03g, 63.2%) as an oil. 1HNMR (CDC13) : 6 1.18 (6H, d, J=6.7Hz) , 2 . 92 (1H, m) , 3. 4 8 (3H, s) , 5.21(2H, s) , 6.71(1H, d, J=l6.0Hz), 7.05(2H, d, J=8.8Hz), 7.51(2H, d, J=8.8Hz), 7.58(1H, d, J=16.0Hz). MS (ESI+) : m/z 257 (M+Na). Example 1-2 (1S,2R)- and (1R,2S)-1,2-epoxy-l-[4-(methoxymethoxy)-phenyl]-4-methyl-3-pentanone 30% H2O2 (1.7ml) and 3M sodium hydroxide aqueous solution (1.7ml) was added to a solution of (IE)-1-[4-(methoxymethoxy)phenyl]-4-methyl-l-penten~3-one obtained by Example 1-1 (2 . OOg) in ethanol: acetone=3 :1 (34ml). The mixture was stirred at room temperature overnight. The mixture was concentrated in vacuo, and partitioned between ethyl acetate and water. The organic layer was washed with water, saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo to give the target compound (2.03g, 95%) as an oil. 1H NMR (DMS0-d6) : 3.36(3H, s), 3.93(1H, d, J-1.9Hz), 4.00(1H, d, J=1.9Hz), 5.20(2H, s), 7.03(2H, d, J=8.6Hz), 7.30(2H, d, J=8.6Hz). MS (ESI) : m/z 273 (M+Na). Example 1-3 4-[3-Isopropyl-l-(4-methoxyphenyl)-lH-pyrazol-5-yl]- phenol A mixture of (lS,2R)-and (1R,2S)-1,2-epoxy-l-[4-(methoxymeth-oxy)phenyl]-4-methyl-3-pentanone obtained by Example 1-2 (2.10g) and 4-methoxyphenylhydrazine hydrochloride (1.76g) in ethanolracetic acid~20:l (20ml) was stirred at 60°C for 3hrs. The mixture was concentrated in vacuo. To the residue was added ethyl acetate and 1M hydrochloric acid. The whole mixture was treated with activated carbon, and was filtered through a celite pad. The filtrate was partitioned. The organic layer was washed successively with 1M hydrochloric acid, saturated aqueous sodium bicarbonate solution, saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residual solid were collected and washed with ethyl acetate to give the target compound (322.2mg, 12.5%) as a white powder. IHNMR (CDCI3) : d 1.33(6H, d, J=7.0Hz) , 3. 07 (IH, m) , 3. 80 (3H, s) , 5.18 (IH, s) , 6.26(IH, s) , 6.72 (2H, d, J=8.8Hz), 6.83(2H, d, J=9.0Hz), 7.08(2H, d, J=8.8Hz), 7.20(2H, d, J=9.0Hz). MS (ESI+) ; m/z 309 (M+H). Example 2 tert-Butyl 2-{4-[3-isopropyl-l-(4-methoxyphenyl)-1H- pyrazol-5-yl]-phenoxy}ethylcarbamate Diethylazodicarboxylate (259mg) was added to a mixture of 4-[3-isopropyl-l-(4-methoxyphenyl)-IH-pyrazol-5-yl]phenol obtained by Example 1-3 (305mg), 2-t-butoxycarbonylaminoethanol (479mg), and triphenylphosphine (390mg) in tetrahydrofuran (3ml). After stirring at room temperature for 7hrs, diethylazod icarboxylate (17mg) and triphenylphosphine (26mg) was ad ded to the reaction mixture. After stirring at room temperature for lhr, the reaction mixture was concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with 30% ethyl acetate/n-hexane to give the target compound (396mg, 88.5%) as a solid. IHNMR (CDCI3) : br-s), 6.26(1H, s) , 6.76-6.87(4H, m) , 7.14(2H, d, J=8.9Hz), 7.20(2H, d, J=9.0 Hz). Example 3 2-{4- [3-Isopropyl-l-(4-methoxyphenyl)-lH-pyrazol-5-yl]- phenoxyJethanamine hydrochloride 4M Hydrochloric acid/dioxane (2ml) was added to a solution of tert-butyl 2-{4-[3-isopropyl-l-(4-methoxy-phenyl)-lH-pyrazol-5-yl]-phenoxy}ethylcarbamate obtained by Example 2 (382mg) in dichloromethane (3ml) at 0°C. After stirring at room temperature for lhr, the reaction mixture was concentrated in vacuo. The residue was crystallized from a mixture of isopropanol and ethyl acetate to give the target compound (311mg, 94.7%) as a powder. 1H NMR (DMS0-d6) : 6 1.27(6H, d, J=6.9Hz), 2.95(1H, m) , 3.14-3.22(2H, m) , 3.76(3H, s) , 4.14-4.20(2H, m) , 6.41(1H, s), 6.93(4H, d, J=8.9Hz), 7,16(4H, d, J=8.9Hz), 8.22(2H, br-s). MS (ESI+) : m/z 352 (M+H). Example 4 N- (2-{4-[3-Isopropyl-l-(4-methoxyphenyl)-lH-pyrazol-5- yl]phenoxy}-ethyl)methanesulfonamide Methanesulfonyl chloride (32.2mg) was added to a solution of 2-{4-[3-isopropyl-l-(4-methoxyphenyl)-1H-pyrazol-5-yl]phenoxy}ethanamine hydrochloride obtained by Example 3 (90.9mg) and triethylamine (71-lmg) in dichloromethane (2ml). The mixture was stirred at room temperature for 2hrs. The mixture was concentrated in vacuo, and the residue was partitioned between ethyl acetate and a mixture of IM hydrochloric acid and brine. The aqueous layer was reextracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium bicarbonate solution, and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was crystallized from a mixture of ethyl acetate and isopropylether to give the target compound (78.0mg, 77.5%) as a white powder. MP : 162-163^. 1H NMR (DMS0-d6) : 6 1.26(6H, d, J=6.9Hz), 2.94(3H, s) , 2.94(1H, m), 3.25-3.39(2H, m) , 3.76(3H, s) , 3.98-4.04(2H, m) , 6.4 0(1H, s) , 6.90 (2H, d, J=8.8Hz), 6.93(2H, d, J=8.9Hz), 7.13(2H, d, J=8.8Hz), 7.15(2H, d, J=8.9Hz), 7.27(1H, s). IR (KBr) : 3122, 2966, 2897, 2871, 1614, 1514cm"1. Example 5 N-(2-{4-[3-Isopropyl-l-(4-methoxyphenyl)-lH-pyrazol-5- yl]phenoxy}ethyl)urea Trimethylsilylisocyanate (41.4mg) was added to a solution of 2-{4- [3-isopropyl-l-(4-methoxyphenyl)-1H-pyrazol-5-yl]phenoxy}ethanamine hydrochloride obtained by Example 3 (93.0mg) and triethylamine (72.8mg) in dichloromethane (3ml) and the mixture wasstirred at room temperature for 3hrs. Trimethylsilylisocyanate (8.3mg) was added and the mixture was stirred at room temperature for l*5hrs. Trimethylsilylisocyanate (13.8 mg) and triethylamine (12.1mg) was added and the mixture was stirred at room temperature for 1.5hrs. The mixture was concentrated in vacuo, and the residue was partitioned between chloroform and a mixture of 1M hydrochloric acid and brine. The aqueous layer was extracted with chloroform. The combined organic layer was washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by preparative thin layer silica gel chromatography developed by 10% methanol/chloroform. The separated silica gel was extracted with 10% •nethanol/chlorof ormand the solvent was evaporated in vacuo. The residue was crystallized from a mixture of ethyl acetate and isopropylether to give the target compound (85.7mg, 90.6%) as a white powder. MP : 100-104°C. 1H NMR (DMS0-d6) : 6 1.26(6H, d, J=6.9Hz), 2.94(1H, m) , 3.27-3.36(2H, m) , 3.76(3H, s) , 3.89-3.96(2H, m) , 5.52(2H, s) , 6.14(1H, t, J=5.6Hz) , 6.39(1H, s) , 6.89(2H, d, J=8.7Hz) , 6.93(2H, d, J=8.9Hz), 7.12(2H, d, J=8.7Hz), 7.15(2H, d, J=8.9Hz). IR (KBr) : 3371, 3190, 2964, 2873, 1738, 1684, 1639, 1614, 1543, 1512cm"1. MS (ESI+) : m/z 395 (M+H). Example 6 tert-Butyl 2-{4-[3-(1-hydroxy-l-methylethyl)-1- (4- methoxyphenyl)-lH-pyrazol-5-yl]phenoxy}ethylcarbamate tert-Butyl 2-{4-[3-ethoxycarbonyl-l-(4-methoxy-phenyl)-lH-pyrazol-5-yl]phenoxy}ethylcarbamate (1.37g) in tetrahydrofuran (10ml) was added dropwise to 0.93M. solution of methyl magnesium bromide in tetrahydrofuran (16ml) at 24-27°C with cooling in a waterbath. After stirring at room temperature for Ihr, the mixture was poured into a mixture of saturated aqueous ammonium chloride solution and ice. The mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with 70% ethyl acetate/n-hexane to give the target compound (1.17g, 88%) as an amorphous powder. MS (ESI + ) : m/z 468 (M+H) 1H NMR (CDC13) : d 1.45(9H, s) , 1.65(6H, s) , 2.78(1H, s) , 3.48-3.57(2H, m) , 3.81(3H, s) , 3.97-4.03(2H, m) , 4.97(1H, br), 6.36(1H, s), 6.78-6.89 (4H, m) , 7.13(2H, df J=8.7Hz), 7.21(2H, d, J=8.9Hz). Example 7 tert-Butyl 2-{4-[3-isopropenyl-l-(4-methoxyphenyl)-1H- pyrazol-5-yl]phenoxyjethylcarbamate Methanesulfonyl chloride (367mg) and triethylamine (649mg) were added successively to a solution of tert-butyl 2-{4-[3-(1-hydroxy-l-methylethyl)-1-(4-methoxy¬phenyl) -lH-pyrazol-5-yl]phenoxy}ethylcarbamate obtained by Example 6 (l.Og) and N,N-dimethylformamide (91.5mg) in dichloromethane (10ml) and the mixture was stirred at room temperature for 2hrs. Additional methanesulfonyl chloride and triethylamine were added until all starting material was consumed with stirring at the same temperature. The reaction mixture was partitioned between ethyl acetate and 1M hydrochloric acid, and the organic layer was washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with 30% ethyl acetate/n-hexane to give the target compound (900mg, 93.6%) as an amorphous powder. 1H NMR (CDCI3) : 6 1.45(9H, s) , 2.21(3H, s) , 3. 48-3. 57 (2H, m) , 3.81(3H, s) , 3.97-4.03 (2H, m) , 4.98 (1H, br-s), 5.12(1H, br-s) , 5.59(1H, br-s), 6.56(1H, s), 6.77-6.87(4H, m) , 7.14(2H, d, J=8.7Hz), 7.22(2H, d, J=8.9Hz). MS (ESI+) : m/z 450 (M+H). Example 8 tert-Butyl 2-{4- [3-isopropyl-l-(4-methoxyphenyl) -1H- pyrazol-5-yl]phenoxy}ethylcarbamate A mixture of 10% Pd-C 50% wet (65mg) and tert-butyl 2-{4-[3-isopropenyl-l-(4-methoxyphenyl)-1H-pyrazol-5-yl]phenoxyjethylcarbamate obtained by Example 7 (64 5mg) in tetrahydrofuran (2ml) and methanol (4ml) was hydrogenated under H2 latm at room temperature for 3hrs. The catalyst was removed by filtration. The filtrate and combined washings were concentrated in vacuo. The residue was crystallized from a mixture of ethyl acetate and isopropyl ether to give the target compound (37Omg, 57.1%) as a white powder. 1HNMR (CDCI3) : 6 1.34 (6H, d, J=7.0Hz) , 1.4 5 (9H, s) , 3.07 (1H, m) , 3.4 8-3.57(2H, m) , 3.80(3H, s) , 3.97-4.03(2H, m) , 4.97(1H, br-s), 6.26(1H, s) , 6.7 6-6.87(4H, m) , 7.14(2H, d, J-8.9Hz), 7.20(2H, d, J=9.0Hz). MS (ESI+) : m/z 452 (M+H). Example 9 tert-Butyl 2-{4-[3-(1-hydroxy-l-methylethyl)-1-(6-methoxy-3-pyridinyl)-lH-pyrazol-5-yl]phenoxy}ethyl¬carbamate The title compound (624.4mg, 42.9%) was prepared as an amorphous powder f rom tert-butyl 2-{ 4- [3- (1-hydroxy-l-methylethyl)-1-(6-methoxy-3-pyridinyl)-lH-pyrazol-5-yl]phenoxy}ethylcarbamate in a similar manner to that of Example 6. 1H NMR (CDC13) : 6 1.45(9H, s), 1.65(6H, s), 3.49-3.57(3H, m), 3.93(3H, s), 3.98-4.04(2H, m) , 4.98(1H, br), 6.39(1H, s), 6.72(1H, d, J=8.8Hz), 6.83(2H, d, J=8.8Hz), 7.15(2H, d, J=8.8Hz), 7.54(1H, dd, J=2.8, 8.8Hz), 8.07(1H, d, J=2.8Hz). MS(ESI+) : 469 (M+H). Example 10 tert-Butyl 2-{4-[3-isopropenyl-l-(6-methoxy-3- pyridinyl)-lH-pyrazol-5-yl]phenoxy}ethylcarbamate The title compound (495mg, 85.7%) was prepared as an oil from tert-butyl 2-{4-[3-(1-hydroxy-1-methylethyl)-1-(6-methoxy-3-pyridinyl)-lH-pyrazol-5-yl]phenoxy}-ethylcarbamate obtained by Example 9 in a similar manner to that of Example 7. 1H NMR (CDCI3) : 6 1.45(9H, s) , 2.20(3H, s) , 3.49-3.57(2H, m) , 3.92(3H, s) , 3.98-4.04(2H, m) , 4.99(1H, br-s), 5.15(1H, br-s), 5.60(1H, br-s), 6.58(1H, s) , 6.72(1H, d, J=8.8Hz), 6.83(2H, d, J-8.7HZ), 7.15(2H, d, J=8.7Hz), 7.55(1H, dd, J=2.6, 8.8Hz), 8.09(1H, d, J=2.6Hz). MS (ESI+) : m/z 451 (M+H). Example 11 tert-Butyl 2-{4-[3-isopropyl-l-(6-methoxy~3-pyridinyl)- lH-pyrazol~5~yl]phenoxy}ethylcarbamate The title compound (220mg, quant.) was prepared as a n amorphous powder from tert-butyl 2-{4-[3-isopropenyl-1-(6-methoxy~3-pyridinyl)-lH-pyrazol-5-yl]phenoxy}-ethylcarbamate obtained by Example 10 in a similar manne r to that of Example 8. IHNMR (CDC13) : d 1.34 (6H, d, J=6.8Hz) , 1.45 (9H, s) , 3.07 (IH, m) , 3.48-3.57 (2H, m) , 3.92(3H, s), 3.98-4.04(2H, m) , 4.98 (IH, br) , 6.28(IH, s) , 6.71(IH, d, J=8.9Hz), 6.82(2H, d, J=8.9Hz), 7.14(2H, d, J=8.9Hz), 7.56(1H, dd, J=2.6, 8.9Hz), 8.05(1H, d, J=2.6Hz) . MS (ESI+) : m/z 453 (M+H). Example 12 2-{4-[3-Isopropyl-l-(6-methoxy-3-pyridinyl)-lH-pyrazol- 5-yl]phenoxy}ethanamine dihydrochloride The title compound (257mg, quant.) was prepared as a n amorphous powder from tert-butyl 2-{4-[3-isopropyl-l-(6-methoxy-3-pyridinyl)-lH-pyrazol-5-yl]phenoxy}ethyl¬carbamate obtained by Example 11 in a similar manner to that of Example 3. IHNMR (DMSO-d6) : 6 1.27(6H, d, J=6.9Hz), 2.96(1H, m) , 3.15-3.23 (2H, m) , 3.85(3H, s) , 4 .15-4.21(2H, m), 6.47(1H, s)f 6.86(1H, d, J=8.8Hz), 6.97(2H, d, J=8.8Hz), 7.20(2H, d, J=8.8Hz), 7.62(1H, dd, J=2.7, 8.8Hz), 8.01(1H, d, J= 2.7Hz),8.19(2H, s). MS (ESI+) : m/z 353 (M+H). Example 13 N-(2-{4-[3-Isopropyl-l-(6-methoxy-3-pyridinyl)-1H- pyrazol-5-yl]phenoxy}ethyl)urea The title compound (4 9.9mg, 51.6%) was prepared as a white powder from 2-{4-[3-isopropyl-l-(6-methoxy-3-pyridinyl)-lH-pyrazol-5-yl]phenoxy}ethanamine obtained by Example 12 in a similar manner to that of Example 5. MP : 106-107°C. 1H NMR (DMSO-d6) : 6 1.27(6H, d, J=6.9Hz), 2.96(1H, m), 3.27-3.36 (2H, m), 3.85(3H, s), 3.94(2H, t, J=5.5Hz), 5.52(2H, s), 6.15(1H, t, J=5.6Hz), 6.45(1H, s), 6.85(1H, d, J=8.8Hz), 6.93(2H, d, J=8.7Hz), 7.16(2H, d, J=8.7Hz), 7.60(1H, dd, J=2.6, 8.8Hz), 8.02(1H, d, J=2.6Hz). IR (KBr) : 3400, 3390, 3379, 3352, 2960, 1657, 1608, 154 7, 1512, 1500cm"1. MS (ESI+) : m/z 396 (M+H). Example 14-1 5-[4-(Benzyloxy)phenyl]-1-(4-methoxyphenyl)-4,5- dihydro-lH-pyrazol-3-amine Sodium (3.19g) was added portionwise to ethanol (160ml) . After all sodium was dissolved, 4-methoxyphenylhydrazine hydrochloride (14.5g) was added in one portion to the solution. The mixture was stirred at room temperature for lOmin. To this mixture was added 3-(4-benzyloxyphenyl)acrylonitrile (16.3g) in one portion, and the mixture was refluxed for 3days. Insoluble matter was filtered off, and the filtrate was concentrated in vacuo. Ethyl acetate and water were added to-the residue and the mixture was stirred at room temperature for Ihr. Precipitates were collected and washed successively with water, ethyl acetate, and air dried to give the target compound (12.57g, 48.6%) as a powder. 1H NMR (DMS0-d6) : 6 2.49(1H, dd, J=8.3, 16.1Hz), 3.29(1H, dd, J=10.2, 16.1Hz), 3.60 (3H, s) , 4.69(1H, dd, J=8.3, 10.2Hz), 5.06(2H, s) , 5.62(2H, s) , 6.65(4H, s) , 6.97(2H, d, J=8.6Hz), 7.25(2H, d, J=8.6Hz), 7.31-7.48(5H, m) . MS : (ESI+) : m/z 374 (M+H). Example 14-2 5-[4-(Benzyloxy)phenyl]-1-(4-methoxyphenyl)-lH-pyrazol- 3-amine Mn02 (3.5g) was added to a solution of 5-[4-(benzyloxy)phenyl]-1-(4-methoxyphenyl)-4,5-dihydro-lH-pyrazol-3-amine obtained by Example 14-1 (12.54g) in N,N-dimethylformamide (65ml) and the mixture was stirred at 60^ for 2hrs. Mn02 (5.3g) was added and the mixture was stirred at 60°C for lhr. The mixture was filtered through a celite pad and the pad was washed with N, N-dimethy If ormamide. To the filtrate were added ethyl acetate and water, and the mixture was stirred at room temperature for lhr. Precipitates were collected and washed with water and air dried. The obtained powder was suspended in hot isopropylether cooled with stirring, collected and washed with isopropylether to give the target compound (11.70g, 93.8%) as a powder. 1H NMR (DMS0-d6) : 6 3.74(3H, s), 4.84(2H, s), 5.08(2H, s) , 5.7 3(1H, s) , 6.87 (2H, d, J=9.0Hz), 6.96(2H, d, J=9.0Hz), 7.03-7.13(4H/ m), 7.34-7.47(5H, m). MS (ESI+) : m/z 372 (M+H). Example 15 5-[4-(Benzyloxy)phenyl]-1-(4-methoxyphenyl)-N,N- dimethyl-lH-pyrazol-3-amine 37% Aqueous formamide solution (6ml) and sodium cyanoborohydride (1.39g) were added successively to a so lution of 5-[4-(benzyloxy)phenyl]-1-(4-methoxyphenyl)-lH-pyrazol-3-amine obtained by Example 14-2 (2.75g) in methanol 30ml. The reaction mixture was stirred at room temperature for 3days, occasionally adding 37% aqueous formamide solution and sodium cyanoborohydride appropriate amount to consume all starting material. The reaction mixture was concentrated in vacuo, and the residue was partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with 20% ethyl acetate/chloroform to give the target compound (0.88g, 29.8%) as an oil. 1H NMR (DMS0-d6) : 6 2.81(6H, s), 3.75(3H, s), 5.08(2H, s) , 6.03(1H, s) , 6.90(2H, d, J-8.9Hz), 6.97(2H, d, J=8.8Hz), 7.06-7.16(4H, m) , 7.32-7.46(5H, m). MS (ESI+) : m/z 400 (M+H). Example 16 4-[3-(Dimethylamino)-1-(4-methoxyphenyl)-lH-pyrazol-5- yl]phenol A mixture of 5- [4-(benzyloxy)phenyl]-1-(4-methoxy¬phenyl) -N,N-dimethyl-lH-pyrazol-3-amine obtained by Example 15 (0.83g) and 10% Pd-C 50% wet (160mg) in acetic acid (8ml) was hydrogenated under H2 latm at room temperature for lOhrs. The catalyst was removed by filtration. The filtrate and combined washings were concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with 20% ethyl acetate/chloroform and was crystallized from a mixture of isopropylether and ethyl acetate to give the target compound (455mg, 70.8%) as a white powder. 1H NMR (DMSO-d6) : 6 2.80(6H, s) , 3.74(3H, s) , 5.96(1H, s), 6.69(2H, d, J=8.5Hz), 6.89(2H, d, J=9.0Hz), 7.01(2H, d, J=8.5Hz), 7.09 (2H, df J=9.0Hz), 9.64 (1H, s) . MS (ESI+) : m/z 310 (M+H). Example 17 tert-Butyl 2-{4-[3-(dimethylamino)-1-(4-methoxyphenyl)- lH-pyrazol-5-yl]phenoxy}ethylcarbamate The title compound (477.lmg, 99.7%) was prepared as an oil from 4-[3-(dimethylamino)-1-(4-methoxyphenyl)-lH-pyrazol-5-yl]phenol obtained by Example 16 in a similar manner to that of Example 2. 1H NMR (CDCI3) : 8 1.45(9H, s) , 2.93(6H, s), 3.48-3.54(2 H, m) , 3.79(3H, s) , 3. 97-4 . 03 (2H, m) , 4.97(1H, br) , 5.85 (1H, s), 6.79(2H, d, J=8.7Hz), 6.81(2H, d, J=9.0Hz), 7.1 0-7.27 (4H, m) . Example 18 5- [4- (2-Aminoethoxy)phenyl]-1-(4-methoxyphenyl)-N,N- dimethyl-lH-pyrazol-3-amine hydrochloride The title compound (454mg, quant.) was prepared as an amorphous from tert-butyl 2-{4-[3-(dimethylamino)-1-(4-methoxyphenyl)-lH-pyrazol-5-yl]phenoxy}ethyl-carbamate obtained by Example 17 in a similar manner to that of Example 3. 1H NMR (DMSO-d6) : 6 2.83(6H/ s) , 3.16-3.25 (2H, m) , 3.7 5(3H, s), 4.13-4.18 (2H, m) , 6.06(1H, s) , 6.91(2H, d, J=9. 0Hz), 6.94(2H, d, J=8.8Hz), 7.12(2Hr d, J=9.0Hz)f 7.17(2 H, d, J=8.8Hz), 8.05(2H, br-s). MS (ESI + ) : m/z 353 (M+H) . Example 19 N-(2-{4-[3-(Dimethylamino)-1-(4-methoxyphenyl)-1H- pyrazol-5-yl]phenoxy}ethyl)urea The title compound (116mg, 55.7%) was prepared as an amorphous from 5- [4- (2-aminoethoxy)phenyl]-1-(4-methoxyphenyl)-N,N-dimethyl-lH-pyrazol-3-amine hydrochloride obtained by Example 18 in a similar manner to that of Example 75 described later. 1H NMR (DMS0-d6) : 6 2.81(6H, s), 3.29-3.34(2H, m), 3.7 4(3H, s), 3.92(2H, t, J=5.6Hz), 5.53(2H, s) , 6.03(1H, s), 6.15(1H, t, J=5.6Hz), 6.88-6.92(4H, m), 7.04-7.14(4H, m) . IR (neat) : 3344, 3330, 3321, 1658, 1651, 1643, 1612, 1579, 1564, 1554, 1529, 1514cm"1. MS (ESI+) : m/z 396 (M+H). Example 20-1 5-[4-(Methoxymethoxy)phenyl]-1-(4-methoxyphenyl)-4,5- dihydro-lH-pyrazol-3-amine The title compound (4.0g, 57.8%) was prepared as a powder from 3-(4-methoxymethoxyphenyl)acrylonitrile in a similar manner to that of Example 14-1. 1H NMR (DMSO-d6) : 6 2.49(1H, dd, J=8.3, 16.1Hz), 3.30(1H, dd, J=10.3, 16.1Hz), 3.36(3H, s) , 3.59(3H, s) , 4.70(1H, dd, J=8.3, 10.3Hz), 5.16(2H, s), 5.62(2H, s), 6.65(4H, s), 6.97(2H, d, J=8.6Hz), 7.25(2H, d, J=8.6Hz). MS (ESI+) : m/z 328 (M+H). Example 20-2 5- [4- (Methoxymethoxy)phenyl]-1-(4-methoxyphenyl)-1H- pyrazol-3-amine The title compound (4.80g, quant.) was prepared as an oil from 5- [4-(methoxymethoxy)phenyl]-1-(4-methoxy¬phenyl) -4,5-dihydro-lH-pyrazol-3-amine obtained by Example 20-1 in a similar manner to that of Example 14-2. 1H MMR (DMS0-d6) : 6 3.36(3H, s) , 3.74(3H, s) , 4.85(2H, s), 5.18(2H, s) , 5.74(lHf s) , 6.88(2H, d, J=9.0Hz), 6.96 (2H, d, J=8.8Hz), 7.02-7.13(4H, m) . MS (ESI+) : m/z 326 (M+H). Example 21 3-Chloro-5- [4-(methoxymethoxy)phenyl]-1-(4-methoxy- phenyl)-IH-pyrazole A mixture of 5-[4-(methoxymethoxy)phenyl]-1-(4-methoxyphenyl)-lH-pyrazol-3-amine obtained by Example 20-2 (3.79g), lithium chloride (2.47g), and copper (II) chloride (3.13g) in acetonitrile (60ml) was stirred at room temperature for lOmin. To this mixture was added isoamyl nitrite (2.73g), and the mixture was stirred at room temperature for lhr. The mixture was partitioned between ethyl acetate and saturated aqueous ammonium chloride solution. The organic layer was washed with saturated aqueous ammonium chloride solution and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with 30% ethyl acetate/n-hexane. The solvent was evaporated in vacuo. The residue was crystallized from a mixture of isopropyl ether and ethyl acetate to give the target compound (2.38g, 59.3%) as a white powder. 1H NMR (CDC13) : 6 3.48(3H, s) , 3.82(3H, s), 5.17(2H, s), 6.36(1H, s), 6.85(2H, d, J=9.0Hz), 6.95(2H, d, J=8.9Hz), 7.12(2H, d, J-8.9HZ), 7.20(2H, d, J=9.0Hz). MS (ESI + ) : m/z 345 (M+H) . Example 22 4- [3-Chloro-l-(4-methoxyphenyl)-lH-pyrazol-5-yl] phenol To a solution of 3-chloro-5-[4-(methoxymethoxy)-phenyl]-1-(4-methoxyphenyl)-IH-pyrazole obtained by Example 21 (2.35g) in tetrahydrofuran (10ml) and methanol (10ml) was added 36% hydrochloric acid (0.34ml). The reaction mixture was stirred at room temperature for lhr, at 50°C for 1.5hrs, and at 60^ for 1.5hrs. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue solid was collected and washed with a mixture of isopropylether and n-hexane to give the target compound (1.99g, 97.1%) as a white powder. 1H NMR (DMSO-d6) : 6 3.78(3H, s), 6.62(1H, s), 6.71(2H, d, J=8.7Hz), 6.96(2H, d, J=9.0Hz), 7.03(2H, d, J=8.7Hz), 7.19(2H, d, J=9.0Hz), 9.80(1H, s). 200MHz 1H NMR (CDC13) : Example 2 3 2-{4-[3-Chloro-l-(4-methoxyphenyl)-lH-pyrazol-5-yl]- phenoxy}ethanol Sodium hydride 60% dispersion in mineral oil (31.1mg) was added to a solution of 4- [3-chloro-l- (4-methoxyphenyl) -lH-pyrazol-5-yl]phenol obtained by Example 22 (180mg) in N,N-dimethylformamide '(2ml) under cooling in an ice bath. The reaction mixture was stirred at room temperature for Ihr. To the reaction mixture was added a solution of 2-bromoethyl tert-butyl(dimethyl)silyl ether (258mg) in N,N-dimethylformamide (2ml). After stirring at room temperature overnight, the mixture was poured into ice water. The mixture was extracted with ethyl acetate- The organic layer was washed with water and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was dissolved in ethanol (3. 6ml) . To this solution was added 36% aqueous hydrochloric acid (0.3ml). After stirring at room temperature for 3 hrs, the mixture was concentrated in vacuo. The residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic layer was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by preparative thin layer silica gel chromatography developed by 70% ethyl acetate/n-hexane. The separate silica gel was extracted with 10% methanol/chloroform and the solvent was evaporated in vacuo. The residue was crystallized from a mixture of isopropylether and ethyl acetate to give the target compound (136.4mg, 66.1%) as a white powder. MP : 114.7-115.5°C. 1HNMR (DMSO-d6) : 6 3.64-3.73(2H, m), 3.7 7(3H, s), 3.97(2H, t, J=4.9Hz), 4.86(1H, t, J=5.4Hz), 6.68(1H, s) , 6.91(2H, d, J=8.9Hz), 6.96(2H, d, J=8.9Hz), 7.15(2H, d, J=8.9Hz), 7.20 (2H, d, J=8.9Hz) . IR(KBr) : 3521, 1610, 1518cm"1. MS (ESI+) : m/z 345 (M+H). Example 24 tert-Butyl 2-{4- [3-chloro-l-(4-methoxyphenyl)-1H- pyrazol-5-yl]phenoxy}ethylcarbamate The title compound (329.5mg, 22.3%) was prepared as an amorphous from 4-[3-chloro-l-(4-methoxyphenyl)-1H-pyrazol-5-yl]phenol obtained by Example 22 in a similar manner to that of Example 73 described later. 1H NMR (CDC13) : 6 1.45(9H, s) , 3 . 48-3. 57 (2H, m) , 3.81(3H, s), 4.00(2H, t, J=5.1Hz) , 4.96(1H, br), 6.35(1H, s), 6.81(2H, d, J=8.8Hz), 6.84(2H, d, J=8.9Hz), 7.12(2H, d, J=8.8Hz), 7.18(2H, d, J=8.9Hz) . MS (ESI+) : m/z 444 (M+H). Example 25 tert-Butyl 2-{4-[3-chloro-l-(4-methoxyphenyl)-1H- pyrazol-5-yl]phenoxy}ethylcarbamate The title compound (1.31g, 97.8%) was prepared from 4- [3-chloro-l-(4-methoxyphenyl)-lH-pyrazol-5-yl]phenol obtained by Example 22 in a similar manner to that of Example 2. MS (ESI+) : m/z 444 (M+H). Example 2 6 2-{4-[3-Chloro-l-(4-methoxyphenyl)-lH-pyrazol-5-yl]- phenoxy}ethanamine hydrochloride The title compound (605.2mg, 85.4%) was prepared as a white powder from tert-butyl 2-{4-[3-chloro-l-(4-methoxyphenyl)-lH-pyrazol-5-yl]phenoxy}ethylcarbamate obtained by Example 25 in a similar manner to that of Example 3. IHNMR (DMS0-d6) : 6 3.14-3.23(2H, m), 3.78 Example 27 N- (2-{4-[3-chloro-l-(4-methoxyphenyl)-lH-pyrazol-5-yl]- phenoxy}ethyl)methanesulfonamide The title compound (137.8mg, 82.8%) was prepared as a white powder from 2-{4-[3-chloro-l-(4-methoxyphenyl)-lH-pyrazol-5-yl]phenoxyJethanamine hydrochloride obtained by Example 26 in a similar manner to that of Example 4. MP : 117-119°C. IHNMR (DMSO-d6) : 6 2.94 (3H, s) , 3.27-3.34 (2H, m) , 3.7 6 (3H, s), 4.02(2H, t, J=5.5Hz)/ 6.69(1H, s), 6.90-7.01 (4H, m), 7.14-7.25(4H, m) , 7.28(1H," t, J=5.7Hz). IR (KBr) : 1612, 1516cm"1. MS (ESI+) : m/z 422(M+H). Example 28 N-(2-{4- [3-Chloro-l-(4-methoxyphenyl)-lH-pyrazol-5-yl]- phenoxy}ethyl)urea The title compound (174.6mg, 85.8%) was prepared as a white powder from 2-{4-[3-chloro-l-(4-methoxyphenyl)-lH-pyrazol-5-yl]phenoxy}ethanamine hydrochloride obtain ed by Example 26 in a similar manner to that of Example 75 described later. MP : 144. 8-145. 4°C. 1HNMR (DMSO-d6) : 6 3.27-3.34(2H, m) , 3.77(3H, s) , 3.93(2H, t, J=5.5Hz), 5.52(2H, s) , 6.15(1H, t, J=5.7Hz), 6.68(1H, s), 6.92(2H, d, J=9.0Hz), 6.97(2H, d, J=9.0Hz), 7.15(2H, d, J=9.0Hz), 7.20(2H, d, J=9.0Hz). IR (ATR) : 3423, 3402, 3203, 3143, 3010, 2976, 2943, 2885, 1651, 1610, 1583, 1516cm"1. MS (ESI+) : m/z 387 (M+H). Example 29-1 5-[4-(Methoxymethoxy)phenyl]-1-(6-methoxy-3-pyridinyl)- 4,5-dihydro-lH-pyrazol-3-amine The title compound (1.63g, 41.2%) was prepared as a powder from 3-(4-methoxymethoxyphenyl)acrylonitrile and 2-methoxy-5-pyridinylhydrazine dihydrochloride in a similar manner to that of Example 14-1. H NMR (DMS0-d6) : 6 2.48-2.60(1H, dd, overlapping), 3.23-3.34(1H, dd, overlapping), 3.36(3H, s) , 3.68(3H, s), 4.75(1H, dd, J=8.6, 10.0Hz), 5.16(2H, s), 5.77(2H, s), 6.56(1H, d, J=8.8Hz), 6.98(2H, d, J=8.6Hz), 7.15(1H, dd, J=2.8, 8.8Hz), 7.27(2H, d, J=8.6Hz), 7.49(1H, d, J=2.8Hz). MS (ESI+) : m/z 329 (M+H). Example 29-2 5-[4-(Methoxymethoxy)phenyl]-1-(6-methoxy-3-pyridinyl)-lH-pyrazol-3-amine The title compound (1.77g, quant.) was prepared as an oil from 5-[4-(methoxymethoxy)phenyl]-1-(6-methoxy~ 3-pyridinyl)-4,5~dihydro-lH-pyrazol-3-amine obtained by Example 29-1 in a similar manner to that of Example 14-2. 1H NMR (DMS0-d6) : 6 3.37(3H, s) , 3.83(3H, s)f 4.97(2H, s) , 5.19(2H, s) , 5.78 (1H, s) , 6.81(1H, d, J=8.9Hz), 6.99(2H, d, J=8.8Hz), 7.15(2H, d, J=8,8Hz), 7.51(1H, dd, J=2.7, 8.9Hz), 7.92(1H, d, J=2.7Hz). MS (ESI+) : m/z 327 (M+H). Example 30 5-{3-Chloro-5-[4-(methoxymethoxy)phenyl]-lH-pyrazol-1- yl}-2-methoxypyridine The title compound (981.7mg, 57.9%) was prepared as a powder from 5-[4-(methoxymethoxy)phenyl]-1-(6-methoxy-3-pyridinyl)-lH-pyrazol-3-amine obtained by Example 29-2 in a similar manner to that of Example 21. 1H NMR (CDC13) : 8 3.48(3H, s) , 3.93(3H, s), 5.18(2H, s), 6.39(1H, s), 6.74(1H, d, J=8.8Hz), 6.99(2H, d, J=8.8Hz), 7.13(2H, df J=8.8Hz), 7.55(1H, dd, J-2.7, 8.8Hz), 8.05 (1H, d, J=2.7Hz). MS (ESI + ) : m/z 346 (M+H) . Example 31 4- [3-Chloro-l-(6-methoxy-3-pyridinyl)-lH-pyrazol-5-yl]- phenol The title compound (2.15g, 80.5%) was prepared as a white powder from 5-{3-chloro-5-[4-(methoxymethoxy)-phenyl]-lH-pyrazol-1-yl}-2-methoxypyridine obtained by Example 30 in a similar manner to that of Example 22. IH NMR (DMSO~d6) : 6 3.87(3H, s) , 6.68(1H, s), 6.74(2H, d, J=8.6Hz), 6.89(1H, d, J=8.8Hz), 7.07(2H, d, J=8.6Hz), 7.65(1H, dd, J-2.7, 8.8Hz), 8.09(1H, d, J=2.7Hz), 9.86 (IH, br-s). MS (ESI+) : m/z 302 (M+H). Example 32 2-{4-[3-Chloro-l-(6-methoxy-3-pyridinyl)-lH-pyrazol-5- yl]phenoxy}ethanol The title compound (140.9mg, 86%) was prepared as a white powder from 4- [3-chloro-l-(6-methoxy-3-pyridinyl)-lH-pyrazol-5-yl]phenol obtained by Example 31 in a similar manner to that of Example 23. MP : 136.5-138.2°C. IH NMR (DMSO~d6) : 6 3.65-3.74 (2H, m) , 3.87(3H, s), 3.9 8(2H, t, J=4.9Hz), 4.87(1H, t, J=5.5Hz), 6.74(1H, s) , 6. 86-6.98(3H, m) , 7.19(2H, d, J=8.8Hz), 7.67(1H, dd, J=2.8, 8.8Hz), 8.10(1H, d, J=2.8Hz). IR (KBr) : 3369, 2960, 1610, 1502cm"1. MS (ESI+) : m/z 346 (M+H). Example 33 tert-Butyl 2-{4-[3-chloro-l-(6-methoxy-3-pyridinyl)-IH- pyrazol-5-yl]phenoxyJethylcarbamate The title compound (9641119, 93.4%) was prepared as a white solid from 4-[3-chloro-l-(6-methoxy-3-pyridinyl)-lH-pyrazol-5-yl]phenol obtained by Example 31 in a similar manner to that of Example 2. 1H NMR (DMS0-d6) : 6 1.37(9H, s) , 3.22-3.33 (2H, ih) , 3.8 7(3H, s), 3.95(2H, t, J=5.7Hz), 6.74(1H, s) , 6.86-7.04(4 H, m) , 7.19(2H, d, J=8.7Hz), 7.67(1H, dd, J=2.7, 8.8Hz), 8.11(1H, d, J=2.7Hz). MS (ESI + ) : m/z 445 (M+H) . Example 34 2-{4-[3-Chloro-l-(6-methoxy~3-pyridinyl)-IH-pyrazol-5- yl]phenoxy}-ethanamine dihydrochloride The title compound (842mg, 98.6%) was prepared as an amorphous from tert-butyl 2-{4-[3-chloro-l-(6-methoxy-3-pyridinyl)-lH-pyrazol-5-yl]phenoxy}ethylcarbamate obtained by Example 33 in a similar manner to that of Example 3. IH NMR (DMSO-d6) : 6 3.15-3.24(2H, m), 3.87(3H, s) , 4.1 9(2H, tf J=4.9Hz), 6.76(1H, s), 6.90(1H, d, J=8.8Hz), 6. 99(2H, d, J=8.8Hz), 7.23(2H, d, J=8.8Hz), 7.68(1H, d, J= 2.7, 8.8Hz), 8.10(1H, d, J=2.7Hz), 8.20(2H, br-s). MS (ESI+) : m/z 345 (M+H) . Example 35 N- (2-{4-[3-Chloro-l-(6-methoxy-3-pyridinyl)-IH-pyrazol- 5-yl]phenoxy}ethyl)urea The title compound (119.5mg, 62.4%) was'prepared as a white powder from 2-{4-[3-chloro-l-(6-methoxy-3-pyridinyl) -lH-p'yrazol-5-yl] phenoxy} ethanamine dihydrochloride obtained by Example 34 in a similar manner to that of Example 75 described later. MP : 155.6-157.9°C. 1H NMR (DMS0-d6) : 6 3.27-3.34 (2H, m) , 3.87(3H, s) , 3.9 4(2H, t, J=5.5Hz), 5.53(2H, s) , 6.15(1H, t, J=5.5Hz), 6. 75(1H, s), 6.89(1H, d, J=8.8Hz), 6.95(2H, d, J=8.8Hz), 7. 19(2H, d, J=8.8Hz), 7.66(1H, dd, J=2.7, 8.8Hz), 8.11(1H, d, J=2.7Hz). IR (KBr) : 3425, 3415, 3319, 1657, 1610, 1591, 1581, 1574, 1500cm"1. Example 36 5-[4-(Benzyloxy)phenyl]-3-isopropoxy-l-(4-methoxy- phenyl)-lH-pyrazole A mixture of 5-[4-(benzyloxy)phenyl]-3-hydroxy-l-(4-methoxyphenyl)-lH-pyrazol (2.4g), 2-iodopropane (5.4 8g) , and potassium carbonate (2.67g) in N,N-dimethyl- formamide (10ml) was stirred at 100°C for 3hrs. The reaction mixture was poured into ice water and the mixture was extracted with ethyl acetate . The organic layer was washed with water and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with 20% ethyl acetate/n-hexane and the solvent was evaporated in vacuo. The residue was recrystallized from a mixture of ethyl acetate and n-hexane to give the target compound (2.14g, 80.1%) as a white powder. 1H NMR (DMSO-d6) : 6 1.31(6H, d, J=6.1Hz), 3.76(3H, s) , 4.7 5 (1H, m) , 5.08 (2H, s) , 6.00(1H, s) , 6.92(2H, d, J=9.0Hz), 6.97(2H, d, J=8.9Hz), 7 .10-7.16 (4H, m) , 7.34-7.43(5H, m) . MS (ESI + ) : m/z 415 (M+H) . Example 37 4- [3-Isopropoxy-l-(4-methoxyphenyl)-lH-pyrazol-5-yl]- phenol To a solution of ammonium formate (954mg) in water (2ml) were added ethanol (10ml), a solution of 5-[4-(benzyl-oxy)phenyl]-3-isopropoxy-l-(4-methoxyphenyl)-1H-pyrazole obtained by Example 36 (2.09g) in tetrahydrofuran (10ml), and 10% palladium on carbon 50% wet (200mg) successively. The mixture was refluxed for lhr. The catalyst was removed by filtration and washed with ethyl acetate- The filtrate and combined washings were concentrated in vacuo. Ethyl acetate and water were added to the residue. Precipitates were collected and washed with water and ethyl acetate to give the first crop of the target compound (419mg) as a white powder. The filtrate was partitioned, and the organic layer was saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue crystals were collected and washed with isopropylether to give the second crop of the target compound (1.19g, 72.5%) as a white powder. 1H NMR (DMSO-d6) : 6 1.31(6H, d, J=6.2Hz), 3.75(3H, s), 4.75(1H, m), 5.93(1H, s), 6.70(2H, d, J=8.6Hz), 6.91(2H, d, J=9.0Hz) , 7.01(2H, d, J=8.6Hz), 7.11(2H, d, J=9.0Hz), 9.70(1H, s). MS (ESI + ) : m/z 325 (M+H) . Example 38 2-{4- [3-Isopropoxy-l-(4-methoxyphenyl)-lH-pyrazol-5- yl]phenoxy}ethanol The title compound (147.3mg, 88.2%) was prepared as an oil from 4-[3-isopropoxy-l-(4-methoxyphenyl)-1H-pyrazol-5-yl]phenol obtained by Example 37 in a similar manner to that of Example 23. 1H NMR (CDC13) : 8 1.40(6H, d, J=6.2Hz), 2.02(lH,'t, J=5. 8Hz), 3.79(3H, s), 3.94-4.00(2H, m), 4.04-4.10 (2H, m) , 4. 87(1H, m) , 5.85(1H, s) , 6.81(2H, d, J=9.0Hz), 6.82(2H, d, J=8.9Hz), 7.10-7.21(4H, m) . IR (neat) : 3400, 3369, 2974, 2933, 1612, 1514cm"1. MS (ESI+) : m/z 369 (M+H). Example 39 tert-Butyl 2-{4- [3-isopropoxy-l-(4-methoxyphenyl)-1H- pyrazol-5-yl]phenoxy}ethylcarbamate The title compound (520mg, 72.2%) was prepared as a white powder from 4-[3-isopropoxy-l-(4-methoxyphenyl)-lH-pyrazol-5-yl]phenol obtained by Example 37 in a similar manner to that of Example 2. 1H NMR (DMSO-d6) ; 8 1.31(6H, d, J=6.2Hz), 1.37(9H, s) , 3.22-3.3K2H, m) , 3.75(3H, s), 3 . 90-3. 97 (2H, m) , 4.76(1H, m) , 5.99{1H, s), 6.86-6.96(4H, m) , 7.01(1H, t, J=5.6Hz), 7.09-7.15(4H, m). MS (ESI + ) : m/z 467 (M+H) . Example 40 2- {4-[3-Isopropoxy-l-(4-methoxyphenyl)-lH-pyrazol-5- yl]phenoxy}ethanamine hydrochloride The title compound (557mg, quant.) was prepared as an amorphous from tert-butyl 2-{4-[3-isopropoxy-l-(4-methoxyphenyl)-lH-pyrazol-5-yl]phenoxy}ethylcarbamate obtained by Example 39 in a similar manner to that of Example 3. 1H NMR (DMSO-d6) : 6 1.31(6H, d, J=6.1Hz), 3.12-3.28(2H, m) , 3.76(3H, s) , 4.00-4.18(2H, m) , 4.76(1H, m) , 6.01(1H, s), 6.92(2H, d, J=9.0Hz), 6.94(2H, d, J=8.7Hz), 7.10-7, 19(4H, m) , 8.06(2H, br-s) . MS (ESI + ) : m/z 368 (M+H) . Example 41 N- (2-{4-[3-Isopropoxy-l-(4-methoxyphenyl)-lH-pyrazol-5- yl]phenoxy}ethyl)methanesulfonamide The title compound (125mg, 79.8%) was prepared as a white, powder from 2-{4-[3-isopropoxy-l-(4-methoxy¬phenyl) -lH-pyrazol-5-yl]phenoxy}ethanamine hydrochloride obtained by Example 40 in a similar manner to that of Example 4. MP : 167.9-168.0°C. 1H NMR (DMSO-d6) : 6 1.31(6H, d, J=6.1Hz), 2.94(3H, s) , 3.27-3.36 (2H, m), 3.75(3H, s) , 3.98-4.05(2H, m), 4.76(1H, m), 6.0 0(1H, s), 6.88-6.94(4H, m), 7.12(2H, d, J=9.0Hz), 7.14(2 H, d, J=8.9Hz), 7.29(1H, t, J=5.8Hz). IR (KBr) : 3132, 2979, 2939, 1612, 1556, 1518cm"1. MS (ESI+) : m/z 446 (M+H). Example 4 2 N-(2-{4-[3-Isopropoxy-l-(4-methoxyphenyl)-lH-pyrazol-5- yl]phenoxy}ethyl)urea The title compound (7 6.3mg, 50.1%) was prepared as a white powder from 2-{4-[3-isopropoxy-l-(4-methoxy¬phenyl) -lH-pyrazol-5-yl]phenoxy}ethanamine hydrochlorid e obtained by Example 40 in a similar manner to that of Example 75 described later. MP : 139-140°C. 1H NMR (DMSO-d6) : 6 1.31(6H, d, J=6.1Hz), 3.27-3.35(2H, m), 3.75(3H, s) , 3.89-3.96(2H, m), 4.76(1H, m), 5.53(2H, s), 6.00(1H, s), 6.15(1H, t, J=5.7Hz), 6.90(2H, d, J=8. 9Hz), 6.92(2H, d, J=9.0Hz), 7.08-7.15(4H, m). IR (KBr) : 3388, 3350, 3332, 1658, 1612, 1579, 1562, 1554, 1518cm"1. MS (ESI+) : m/z 411 (M+H). Example 4 3 5-[4-(Benzyloxy)phenyl]-1-(6-methoxy-3-pyridinyl)-1H- pyrazol-3-ol To a solution of 3-(4-benzyloxyphenyl)propiolic acid (lg) and 1-hydroxybenzotriazole hydrate (64 3mg) in N-methylpyrrolidone (10ml) was added WSCD-HCl (912mg) and the mixture was stirred at room temperature for lOmin. In another flask, diisopropylethylamine (2.31g) was added to a suspension of 5-hydrazino-2-methoxypyridine dihydrochloride (1.26g) in N-methylpyrrolidone (4ml) and stirred at room temperature until all 5-hydrazino-2-methoxypyridine dihydrochloride was dissolved. Thus obtained hydrazine solution was added to the reaction flask and the mixture was stirred at room temperature for 1.5hrs. The mixture was partitioned between ethyl acetate and 0 . 1M hydrochloric acid, and the aqueous layer was reextracted with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was dissolved in dichloroethane (15ml) and tetrakis(triphenylphosphine)palladium(0) (45.8mg) was added. The mixture was refluxed for lhr and then concentrated in vacuo. The residue was crystallized from ethyl acetate to give the target compound (739mg, 49.9%) as a powder. 1H NMR (DMSO-d6) : 6 3.84(3H, s), 5.10(2H, s), 5.87(1H, s), 6.83'(1H, d, J=8,7Hz), 7.00(2H, d, J=8.7Hz), 7.16(2H, d, J=8.7Hz), 7.29-7.4 8 (5H, m) , 7.54 (1H, dd, J=2.6, 8.7Hz), 7.97(1H, d, J=2.6Hz), 10.13(1H, s). MS (ESI + ) : m/z (M+H) . Example 4 4 5-{5-[4-(Benzyloxy)phenyl]-3-isopropoxy-lH-pyrazol-l- yl}-2-methoxypyridine The title compound (1.33g, quant.) was prepared as a powder from 5-[4-(benzyloxy)phenyl]-1-(6-methoxy-3-pyridinyl)-lH-pyrazol-3-ol obtained by Example 43 in a similar manner to that of Example 36. 1H NMR (CDC13) : 8 1.40(6H, d, J=6.2Hz), 3.92(3H, s) , 4. 86(1H, m) , 5.05(2H, s) , 5.87(1H, s) , 6.69(1H, df J=8.8H z), 6.9K2H, d, J=8.8Hz), 7.15(2H/ d, J=8.8Hz), 7.35-7.4 3(5H, m) , 7.51(1H, dd, J=2.7, 8.8Hz), 8.04(1H, d, J=2.7H z) -MS (ESI+) : m/z 416 (M+H) . Example 4 5 4-[3-Isopropoxy-l-(6-methoxy-3-pyridinyl)-lH-pyrazol-5- yl]phenol The title compound (442.5mg, 54.9%) was prepared as a powder from 5-{5- [4- (benzyloxy)phenyl]-3-isopropoxy-lH-pyrazol-l-yl}-2-methoxypyridine obtained by Example 44 in a similar manner to that of Example 37. 1H NMR (CDCI3) : (5 1.40(6H, d, J=6.2Hz), 3.91(3H, s) , 4. 84(1H, m) , 5.80(1H, s), 5.87(1H, s) , 6.71(1H, d, J=8.8H z), 6.75(2H, d, J=8.6Hz), 7.08(2H/ d, J=8.6Hz), 7.55(1H, dd, J=2.7, 8-8Hz), 8.00(1H, d, J=2.7Hz). MS (ESI+) : m/z 326 (M+H) . Example 4 6 2-{4-[3-Isopropoxy-l-(6-methoxy-3-pyridinyl)-1H- pyrazol-5-yl]phenoxy}ethanol The title compound (94.6mg, 52.2%) was prepared as a white powder from 4-[3-isopropoxy-l-(6-methoxy-3-pyridinyl)-lH-pyrazol-5-yl]phenol obtained by Example 45 in a similar manner to that of Example 23. MP : 74-75°C. 1H NMR (CDC13) : 6 1.40(6H, d,-J=6.1Hz), 1.99(1H, t, J=6. 1Hz) , 3.91(3H, s), 3.94-4.00(2H, m), 4.05-4.11(2H, m), 4. 86(1H, m), 5.88(1H, s) , 6.69(1H, d, J=8.7Hz), 6.85(2H, d, J=8.7Hz), 7.15(2H, d, J=8.7Hz), 7.51(1H, dd, J=2.7, 8.7 Hz), 8.03(1H, d, J=2.7Hz). IR (KBr) : 3350, 1612, 1512, 1500cm"1. MS (ESI+) : m/z 370 (M+H). Example 4 7 tert-Butyl 2-{4-[3-isopropoxy-l-(6-methoxy-3- pyridinyl)-lH-pyrazol-5-yl]phenoxy}ethylcarbamate The title compound (515.3mg, 87.6%) was prepared as a powder from 4-[3-isopropoxy-l-(6-methoxy-3-pyridinyl)-lH-pyrazol-5-yl]phenol obtained by Example 45 in a similar manner to that of Example 2. 1H NMR (DMSO-d6) : 6 1.32(6H, d, J=6.2Hz)/ 1.37(9H, s) , 3.22-3.34(2H, m) , 3.84(3H, s), 3.92(2H, t, J=5.7Hz), 4.7 7(1H, m), 6.06(1H, s)f 6.84(lHf d, J=8.8Hz), 6.91(2H, d, J=8.8Hz), 7.01(1H, t, J=5.5Hz), 7.16(2Hf df J=8.8Hz)/ 7. 58(1H, dd, J=2.7, 8.8Hz)f 7.99(1H/ df J=2.7Hz). Example 4 8 2-{4-[3-Isopropoxy-l-(6-methoxy-3-pyridinyl)-1H- pyrazol-5-yl]phenoxy}ethanamine dihydrochloride The title compound (531mg, quant.) was prepared as an amorphous from tert-butyl 2-{4-[3-isopropoxy-l-(6-methoxy-3-pyridinyl)-lH-pyrazol-5-yl]phenoxy}ethyl-carbamate obtained by Example 4 7 in a similar manner to that of Example 3. 1H NMR (DMS0-d6) : 6 1.32(6H, d, J=6.1Hz), 3.15-3.24(2H, m), 3.84(3H, s), 4.19(2H, t, J=4.9Hz), 4.77(1H, m), 6.0 7(1H, s), 6.85(1H, d, J=8.8Hz), 6.97(2H, d, J=8.8Hz), 7. 21(2H, d, J=8.8Hz), 7.60(1H, dd, J=2.7, 8.8Hz), 7.99(1H, d, J=2.7Hz), 8.22(2H, br-s). MS (ESI+) : m/z 369 (M+H). Example 4 9 N-(2-{4-[3-Isopropoxy-l-(6-methoxy-3-pyridinyl)-1H- pyrazol-5-yl]phenoxy}ethyl)urea The title compound (81.4mg, 60.2%) was prepared as a white powder from 2-{4-[3-isopropoxy-l-(6-methoxy-3-pyridinyl)-lH-pyrazol-5-yl]phenoxyJethanamine dihydrochloride obtained by Example 48 in a similar manner to that of Example 75 described later. MP : 120^. 1H NMR (DMSO-d6) : m) , 3.84(3H, s), 3.94(2H, t, J=5.5Hz), 4.77(1H, m), 5.5 2(2H, s), 6.06(1H, s), 6.15(1H, t, J=5.6Hz), 6.84(1H, d, J=8.8Hz), 6.93(2H, d, J=8.8Hz), 7.17(2H, d, J=8.8Hz), 7. 58(1H, dd, J=2.7, 8.8Hz), 7.99(1H, d, J=2.7Hz). IR (KBr) : 3400, 3330, 1658, 1612, 1514, 1500cm"1. MS (ESI+) : m/z 412 (M+H). Example 50 N- (2-{4-[3-Isopropoxy-l-(6-methoxy-3-pyridinyl)-1H- pyrazol-5-yl]phenoxy}ethyl)methanesulfonamide The title compound (94.4mg, 58.4%) was prepared from 2-{4-[3-isopropoxy-l-(6-methoxy-3-pyridinyl)-1H-pyrazol-5-yl]phenoxy}ethanamine dihydrochloride obtained by Example 48 in a similar manner to that of Example 4 . MP : 121.0-121.6°C. 1H NMR (DMS0-d6) : 6 1.32(6H, d, J=6.1Hz), 2.94(3H, s) , 3.29-3.34(2H, m) , 3.84(3H, s), 4 . 00-4.06 (2H, m), 4.77(1H, m) , 6.06(1H, s), 6.85(lHf d, J=8.7Hz), 6.94(2H, d, J=8. 8Hz), 7.18(2H, d, J=8.8Hz), 7.28(1H, br-s), 7.58(1H, dd, J=2.7, 8.7Hz), 7.99(1H, d, J=2.7Hz). IR (KBr) : 3242, 1612, 1514, 1502cm"1. MS (ESI+) : m/z 447 (M+H). Example 51 2-{4-[1-(4-Chlorophenyl)-3-(trifluoromethyl)-1H- pyrazol-5-yl]phenyl}ethyl methanesulfonate To a solution of 2-{ 4-[1-(4-chlorophenyl)-3-(trifluoromethyl)-lH-pyrazol-5-yl]phenyl}ethanol (2.72 g) and triethylamine (1.55ml) in dichloromethane (30ml) was added dropwise methanesulfonyl chloride (0.86ml) under ice-cooling. The reaction mixture was allowed to warm to room temperature and stirred for lhr. The reaction mixture was quenched with water. The organic layer was separated and washed with IN hydrochloric acid and water, dried over sodium sulfate, filtered and evaporated under reduced pressure to give the target compound (3.25g, 98.5%). 1 HNMR (CDCI3) : 6 2.929( 3H, s) , 3.072(2H, t, J=6.7Hz), 4.427(2H, t, J=6.7Hz), 6.739(1H, ), 7.175(2H, d, J=8.4H z), 7.234(2H, d, J=8.4Hz), 7.253(2H, d, J=8.9Hz), 7.344 (2H, d, J=8.8Hz). MS (ESI+): m/z 467 (M+Na) . Example 52 2- (2~{4-[1-(4-Chlorophenyl) -3-(trifluoromethyl)-1H- pyrazol-5-yl]phenyl}ethyl)-lH-isoindole-1,3(2H)-dione A mixture of 2-{4-[1-(4-chlorophenyl)-3-(trifluorom ethyl)-lH-pyrazol-5-yl]phenyl}ethyl methanesulfonate obtained by Example 51 (3.2g) and Potassium phthalimide (1.6g) was stirred at 80°C for 5hrs. After cooling, the mixture was diluted with water and ethyl acetate. The aqueous layer was separated and extracted with ethyl acetate (twice) . The combined organic layer was washed with water (twice) and brine, dried over magnesium sulfate, filtered and evaporated under reduced pressure to give the target compound (1.55g, 43.5%) as a powder. 1H NMR (CDCI3) : Example 53 2-{4-[l-(4-Chlorophenyl)-3-(trifluoromethyl)-1H- pyrazol-5-yl]phenyl}ethanamine A mixture of 2-(2-{4-[1-(4-chlorophenyl)-3-(trifluoromethyl)-lH-pyrazol-5-yl]phenyl}ethyl)-1H-isoindole-1,3(2H)-dione obtained by Example 52 (1.5g) and hydrazine (2.93ml) in acetonitrile (30ml) was stirred at 60°C for 5hrs. After cooling, the mixture was filtered and washed with acetonitrile. The filtrate was evaporated under reduced pressure to give the target compound (l.lg, quant.) as an oil. IH NMR (CDC13) : 6 3.09(2H, dd, J=5.6Hz, 9.3Hz), 3.24 (2H, dd, J=5.6Hz, 8.6Hz), 5.47(2H, s) , 6.69(1H, s), 7.12(1H, d, J=8.2Hz), 7.21(1H, d, J=8.2Hz), 7.22(1H, d, J=8.9Hz), 7.32(1H, d, J-8.9HZ). MS (ESI+) : m/z 366 (M+l) . Example 54 N- (2-{4-[1-(4-Chlorophenyl)-3-(trifluoromethyl)-1H- pyrazol-5-yl]phenyl}ethyl)methanesulfonamide To a solution of 2-{4-[1-(4-chlorophenyl)-3-(trifluoromethyl)-lH-pyrazol-5-yl]phenyl}ethanamine obtained by Example 53 (400mg) and triethylamine (0.46ml) in dichloromethane (20ml) was added dropwise methanesulfonyl chloride (0.25ml) at room temperature. After stirring for Ihr, the reaction mixture was quenched with IN hydrochloric acid. The aqueous layer was separated and extracted twice with chloroform. The combined organic layer was washed with IN hydrochloric acid, sodium hydrogencarbonate solution, water, dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel (ch1oroform/methanol=4:1) to give the target compound (166mg, 34.2%) as an oil. 1H NMR (CDC13) : 5 2.899(3H, s), 2.904(2H, t, J=6.9Hz), 3. 417(2H, dt, J=6.7 ,6.8Hz), 4.272(1H, t, J=6.1Hz), 6.737 (1H, s), 7.178(2H, d, J=8.4Hz), 7.21(2H, d, J=8.4Hz), 7. 255(2H, d, J=8.8Hz), 7.35(2H, d, J=8.8Hz). IR (Film) : 3346, 1657, 1597, 1552, 1496, 1471, 1236, 1163, 1136, 1092, 978, 835, 756 cm"1. MS (ESI-) : 442 (M-l) . Example 55 N- (2-{4-[1-(4-Chlorophenyl)-3-(trifluoromethyl)~1H- pyrazol-5-yl]phenyl}ethyl) urea To a solution of 2-{4-[1-(4-chlorophenyl)-3-(trifluoromethyl)-lH-pyrazol-5-yl]phenyl}ethanamine obtained by Example 53 (300mg) and triethylamine (0.57ml) in dichloromethane (10ml) was added dropwise trimethylsilyl isocyanate (0.555ml) at room temperature. After stirring overnight, the reaction mixture was quenched with IN hydrochloric acid. Aqueous layer was separated and extracted twice with chloroform. The combined organic layer was washed with IN hydrochloric acid, sodium hydrogencarbonate solution, water, dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel (chloroform/methanol=4:1) to give the target compound (205mg, 61.1%) as an amorphous. 1H NMR (CDCI3) : 8 2.83(2H, t, J=7Hz) , 3.43(2H, dt, J=6.6 Hz, 6.8Hz), 4.41(2H, s) , 4.61(1H, t, J=5.4Hz), 6.72(1H/ s), 7.16(4H, s), 7.25(2H, d, J=8.8Hz), 7.34(2H, d, J=8.8 Hz) . IR (Film): 3346, 1657, 1597, 1552, 1496, 1471, 1448, 1375, 1271, 1236, 1163, 1136, 1092, 978, 835, 756 cm"1. MS (ESI+) : m/z 431 (M+Na) . Example 56 4- [1- (4-Methoxyphenyl)-3-(trifluoromethyl)-lH-pyrazol- 5-yl]benzonitrile A mixture of 4- (4,4,4-trifluoro-3-oxobutanoyl)-benzonitrile (l.Og), 4-methoxyphenylhydrazine hydrochloride (760mg), and sodium acetate (357mg) in acetic acid (10ml) was stirred at 80^ for 4hrs. After cooling, the reaction mixture was poured into water and ethyl acetate. The aqueous layer was extracted twice with ethyl acetate. Combined organic layers were washed with saturated sodium hydrogencarbonate solution (twice), water and brine, dried over sodium sulfate, and evaporated under reduced pressure to give crude product. The crude product was column chromatographed on silica gel (50ml, n-hexane:ethyl acetate=5:1-4:1) and triturate with petroleum ether to give the target compound (553mg, 38.8%). 1H NMR (CDCI3) : d 3.84(3H, s) , 6.82(1H, s) , 6.9(2H, d, J=9Hz), 7.2(2H, d, J=9Hz), 7.33(2H, d, J=8.6Hz), 7.62(2H, d, J=8.6Hz) . IR (Film) : 2229, 1610, 1512, 1468, 1240, 1161, 1132, 839 cm"1. MS (ESI+) : m/z 366 (M+Na) . Example 57 4-[1- (4-Methoxyphenyl)-3-(trifluoromethyl)-lH-pyrazol- 5-yl]benzyl-amine hydrochloride A mixture of 4-[1-(4-methoxyphenyl)-3-(trifluoro¬methyl) -lH-pyrazol-5-yl]benzonitrile obtained by Example 56 (430mg), Pd/C (lOOmg) and IN hydrochloric acid (1.3ml) in methanol (43ml) was stirred under Hydrogen atmosphere for 5hrs. The reaction mixture was filtered with paper filter, and filtrate was evaporated. After dissolving in methanol, the solution was filtered with membrane filter. The filtrate was evaporated to give the target compound (450mg, 93.6%) as crystals. 1H NMR (CDC13) : d, J=9Hz), 7.42 (2H, d, J=9Hz) . IR (Film) : 2964, 1512, 1468, .1238, 1161, 1130, 976, 837 cm"1. MS (ESI+) : m/z 331 (M-CI-NH3) • Example 58 N-{4- [1-(4-Methoxyphenyl)-3-(trifluoromethyl)-1H- pyrazol-5-yl]benzyl}methanesulfonamide To a solution of 4-[1-(4-methoxyphenyl)-3-(trifluoromethyl)-lH-pyrazol-5-yl]benzylamine hydrochloride obtained by Example 57 (lOOmg) and triethylarnine (0.073ml) in chloroform (10ml) was added dropwise methanesulfonyl chloride (0.04ml) at room temperature. After stirring for lhr, the reaction mixture was partitioned between chloroform and water. The organic layer was washed with water, sodium bicarbonate solution, brine, driedovermagnesiumsulfate, filtereda'ndevaporated under reduced pressure to give the target compound (90mg, 81.2%) as an oil. 1H NMR (CDC13) : (2H, d, J=8.3Hz). IR (Film) : 3282, 1514, 1321, 1240, 1151, 974, 837cm"1. MASS (ESI+) : m/z 426 (M+l). Example 59 4-[3-(Difluoromethyl)-1-(4-methoxyphenyl)-lH-pyrazol-5- yl]benzonitrile The title compound (4.5g, 20.6%) was prepared from 4-(4,4-difluoro-3-oxobutanoyl)benzonitrile in a similar manner to that of Example 56. 1H NMR (CDC13) : 6 3.84(3H, s), 6.77(1H, t, J=54.9Hz), 6. 8(1H, s), 6.9(2H, d, J=9Hz), 7.19(2H, d, J=9Hz), 7.33(2H, d, J=8.6Hz), 7.61(2H, d, J=8.6Hz). MS (ESI+) : m/z 348 (M+Na). Example 60 l-{4- [3-(Difluoromethyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl]phenyl}methanamine hydrochloride The title compound (510mg, 45-4%) was prepared from 4-[3-(difluoromethyl)-1-(4-methoxyphenyl)-lH-pyrazol-5-yl]benzonitrile obtained by Example 59 in a similar manner to. that of Example 57 . 1H NMR (DMS0-d6) : 6 3.35(3H, s) , 3.79(2H, s), 7.1(1H, t, J=54.5Hz), 6.95(1H, s) , 6.99(2H, d, J=8.8Hz), 7.26(2H, d, J=8.8Hz), 7.3(2H, d, J=8.3Hz)/ 7.49(2H, d, J=8.3Hz). MS (ESI-): m/z 365 (M-HC1). Example 61 N-{4-[3-(Difluoromethyl)-1-(4-methoxyphenyl)-1H- pyrazol-5-yl]benzyl}methanesulfonamide The title compound (14 6mg, 65-5%) was prepared from 1-{4-[3-(difluoromethyl)-1-(4-methoxyphenyl)-IH-pyrazol -5-yl]phenylJmethanamine hydrochloride obtained by Example 60 in a similar manner to that of Example 58. 1H NMR (CDC13) : 6 2.90(3H, s), 3.82(3H, s) f 4.31(2H, d, J=6.2Hz), 4.73(1H, t, J=6.2Hz), 6.72(1H, s), 6.77(1H, t, J=55Hz), 6.86(2H, d, J=9Hz), 7.19(2H, d, J=9Hz) , 7.22(2 H, d, J=8.4Hz), 7.30(2H, d, J=8.4Hz). IR (film) : 3143, 1518, 1508, 1452, 1325, 1244, 1151, 10 74, 1022, 972, 843, 793 cm"1. MS (ESI-) : m/z 406 (M-l) . Example 62 N-{4-[3-(Difluoromethyl)-1-(4-methoxyphenyl)-1H-pyrazol-5-yl]benzyl}urea To a solution of l-{4-[3-(difluoromethyl)-1-(4-methoxyphenyl) -lH-pyrazol-5-yl] phenyl}xnethanamine hydrochloride obtained by Example 60 (lOOmg) in dichloromethane (1ml) was added dropwise triethylamine (0.163ml) and trimethylsilyl isocyanate (0.11ml) at room temperature. The mixture was stirred at room temperature overnight and quenched by adding saturated sodium hydrogencarbonate solution (0.5ml). The mixture was filtered by Chemelute. The elution was evaporated and purified by preparative thin layer chromatography (0.5mm, 10% methanol/chloroform) to give solid. The solid was added ethyl acetate and n-hexane, and the precipitate was collected by filtration to give the target compound(160mg, 62.9%). 1HNMR (CDC13) : 6 3.82(3H, s) , 4.35(2H, d, J=6Hz) , 4.46( 2H, br-s) , 4.99(1H, t, J=6Hz) , 6.69(1H, s) , 6.76(1H, t, J=55.1Hz) , 6.86(2H, d, J=9Hz), 7.14-7.21(6H, m). MS (ESI+) : m/z 395 (M+Na). IR (film) : 1657, 1608, 1593, 1550, 15120, 1510, 1467, 1338, 1252, 1171, 1088, 1030, 837, 796cm"1. Example 63 4-[1-(4-Methylphenyl)-3-(trifluoromethyl)-lH-pyrazol-5- yl]benzonitrile The title compound (942mg, 86.8%) was prepared from 4-(4,4,4-trifluoro-3-oxobutanoyl)benzonitrile in a similar manner to that of Example 56. 1H NMR (CDCI3) : 6 2.39(3H, s), 6.82(1H, s), 7.15(2H, d, J=8.9Hz), 7.21(2H, d, J=8.8Hz), 7.33(2H, d, J=8.3Hz), 7. 62(2H, d, J=8.3Hz). MS (ESI+): m/z 328 (M+l). Example 64 l-{4-[1-(4-Methylphenyl)-3-(trifluoromethyl)-1H- pyrazol-5-yl]phenylJmethanamine hydrochloride The title compound (414mg, 92.1%) was prepared from 4-[1-(4-methylphenyl)-3-(trifluoromethyl)-lH-pyrazol-5-yljbenzonitrile obtained by Example 63 in a similar manner to that of Example 57. 1H NMR (DMS0-d6) : Example 65 N-{4-[1-(4-Methylphenyl)-3-(trifluoromethyl)-1H- pyrazol-5-yl]benzyl}urea The title compound (81mg, 31.8%) was prepared from l-{4-[1-(4-methylphenyl)-3-(trifluoromethyl)-IH-pyrazol -5-yl]phenyl}methanamine hydrochloride obtained by Example 64 in a similar manner to that of Example 62. 1H NMR (CDCI3) : 6 2.36(3H, s), 4.35(2H, d, J=5.9Hz), 4. 50(2H, br-s), 5.02(1H, t, J=5.5Hz), 6.71(1H, s), 7.16(4H, s), 7.20(4H, d, J=5.7Hz). IR (film) : 3344, 1658, 1600, 1552, 1518, 1236, 1159, 11 34 cm"1. MS (ESI+) : m/z 397 (M+Na) . Example 66 4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-IH-pyrazol-l- yl]benzonitrile The title compound (1.05g, 73.8%) was prepared from 4-methyl-1-(4,4,4-trifluoro-3-oxobutanoyl)benzene in a similar manner to that of Example 69 described later. MP : 125.0-125.5°C. 1H NMR (CDC13) : 6 2.39(3H, s), 6.74( 1H, s) , 7.10(2H, d, J=8.1Hz), 7.19(2H, d, J=8.2Hz), 7.45(2H, d, J=8.7Hz), 7. 65(2H, d, J=8.7Hz). MASS (ESI+) : m/z 350 (M+Na). Example 67 l-{4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H- pyrazol-1-yl]phenyl}methanamine hydrochloride The title compound (830mg, 92.3%) was prepared from 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-lH-pyrazol-1- yl]benzonitrile obtained by Example 66 in a similar manner to that of Example 70 described later. 1H NMR (DMSO-d6) : 6 2.30(3H, d, J=2.3Hz), 4.07(2H, s), 7.15(1H, s), 7.15(2H, d, J=9.0Hz), 7.21(2H, d, J=8.9Hz), 7.39(2H, d, J=8.5Hz), 7.58(2H, d, J=8.5Hz). MS (ESI+) : m/z 332 (M+l). Example 68 N-{4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H- pyrazol-l-yl]benzyl}urea The title compound (65mg, 31.9%) was prepared from l-{4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-py r a zol-l-yl] phenyl} met hanamine hydrochloride obtained by Example 67 in a similar manner to that of Example 72 described later. 1H NMR (CDC13) : 6 2.34(3H, s) , 4.34(2H, d, J=5.8Hz), 4. 56(2H, br-s), 5.23(1H, t, J=5.8Hz), 6.71(1H, s) , 7.07(2H, d, J=8.7Hz), 7.13(2H, d, J=8.7Hz), 7.24(4H, s). IR (film) : 3344, 1658, 1604, 1552, 1234, 1159, 1134cm"1. MS (ESI+) : 397 (M+Na). Example 69 4-[5-(4-Methoxyphenyl)-3-(trifluoromethyl)-lH-pyrazol- 1-yl]benzonitrile A mixture of 4-methoxy-l-(4,4,4-trifluoro-3-oxobutanoyl)benzene (1.Og), 4-methoxyphenylhydrazine hydrochloride (758mg) and sodium acetate (367mg) in acetic acid (5ml) was stirred overnight at room temperature. After then, the reaction mixture was poured into water and ethyl acetate. The aqueous layer was extracted twice with ethyl acetate. Combined organic layers were washed with water, saturated sodium hydrogencarbonate (twice) and brine, dried over sodium sulfate, and evaporated under reduced pressure to give crude product. The crude product was column chromatographed on silica gel (50ml, n-hexane:ethyl acetate=10:1-5:1) to give the target compound (930mg, 66.7%) . 1H NMR (CDC13) : 8 3.84(3H, s), 6.72(1H, s), 6.9(2H, d, J=8.9Hz), 7.14(2H, d, J=8.9Hz), 7.46(2H, d, J=8.7Hz), 7.66(2H, d, J=8.7Hz). MS (ESI+) : m/z 366 (M+Na). Example 7 0 4-[5-(4-Methoxyphenyl)-3-(trifluoromethyl)-lH-pyrazol- 1-yl]benzylamine hydrochloride A mixture of 4-[5-(4-methoxyphenyl)-3-(trifluoro-methyl)-IH-pyrazol-l-yl]benzonitrile obtained by Example 69 (400mg) and 50% wet pd/C (400mg) in ethanol (10ml) and IN hydrochloric acid (1,2ml) was stirred under hydrogen atmosphere for 8hrs. The mixture was filtered and filtrate was evaporated under reduced pressure. The residue was washed with isopropyl ether to give the target compound (400mg, 89.4%) as a powder. 1H NMR (CDCI3) : 6 3.36(s, 3H), 3.76(d, J=2.4, 2Hz), 6.9 4 (d, J=8.7, 2Hz), 7.12(s, 1H), 7.23(d, J=8.7, 2Hz), 7.39 (d, J=8.4, 2Hz), 7.59(d, J=8.4, 2Hz) . MS (ESI + ) : m/z 348 (M+l) . Example 71 N-{4-[5-(4-Methoxyphenyl)-3-(trifluoromethyl) -1H- pyrazol-1-yl]benzyl}methanesulfonamide To a solution of 4-[5-(4-methoxyphenyl)-3-(trifluoromethyl)-lH-pyrazol-l-yl]benzylamine hydrochloride obtained by Example 70 (150mg) and triethylamine (0.1ml) in dichloromethane (10ml) was added dropwise methanesulfonyl chloride (0.06ml) under ice cooling. After stirring for lhr, the reaction mixture was quenched and partitioned between chloroform and water. The aqueous layer was extracted with chloroform. The combined organic layer was washed with water, IN hydrochloric acid, saturated sodium hydrogencarbonate solution and brine, dried over magnesium sulfate, filtered and evaporated under reduced pressure. The residue was chromatographed by high performanced thin layer chromatography to give the target compound (67mg, 40.3%). 1H NMR (CDC13) : 6 2.9M3H, s) , 3.82(s, 3H) , 4.35(2H, d, J-6.IH2), 4.69(1H, t, J=6.1Hz), 6.69(1H, s), 6.84(2H, d, J=8.6Hz), 7.13(2H, d, J=8.6Hz), 7.32 (2H, d, J=9Hz), 7.3 7(2H, d, J=9Hz). IR (film) : 3207, 1479, 1456, 1323, 1252, 1234, 1146, 1122, 984, 968, 962, 841, 802cm"1. MS (ESI+) : m/z 448 (M+Na). Example 72 N-{4- [5-(4-Methoxyphenyl)-3-(trifluoromethyl)-1H- pyrazol-1-yl]benzylJurea To a solution of 4-[5-(4-methoxyphenyl)-3-(trifluoromethyl)-lH-pyrazol-1-yl]benzylamine hydrochloride obtained by Example 70 (150mg) in water (8ml) and ethanol (4ml) was added sodium cyanate (lOOmg) under ice cooling. After stirring for 3hrs, the reaction mixture was partitioned between chloroform and water. The aqueous layer was extracted with chloroform. The combined organic layer was washed with water and brine, dried over magnesium sulfate, filtered and evaporated under reduced pressure. The residue was chromatographed by high performanced thin layer chromatography to give the target compound (105mg, 69%) . 1H NMR (CDCI3) : 8 3.80(3H, s), 4.35(2H, d, J=5.9Hz), 4. 53(2H, br-s), 5.171(1H, t, J=5.7Hz), 6.68(1H, s), 6.84(2 H, d, J=8.7Hz), 7.12(2H, d, J=8.7Hz), 7.25(4H, s) . MS (ESI + ) : m/z 413 (M+Na) . Example 7 3 tert-Butyl 2-{4-[1-(4-methoxyphenyl)-3-(trifluoro- methyl)-lH-pyrazol-5-yl]phenoxy}ethylcarbamate To solution of 4-[1-(4-methoxyphenyl)-3-trifluoro-methyl-lH-pyrazol-5-yl]phenol (500g) in N,N-dimethyl-formamide (1.5L) was added sodium hydride (dispersion in mineral oil, 77.8g) over 25min under ice cooling. The mixture was warmed to room temperature over lOmin and then stirred at room temperature for 30min. A solution of 2-tert-butoxycabonylaminoethyl bromide (4 69 g)(prepared by reacting di-ter-butyl dicarbonate with 2-bromoethylamine hydrobromide) reaction in N,N-dimethylformamide (300ml) was added to the mixture over lOmin at 25-28°C, and the whole mixture was stirred at 60°C for 6hrs. After allowed to stand overnight, the mixture was poured into a mixture of water (4.5L) and toluene (3L) . The organic layer was separated, and the aqueous layer was extracted with toluene (1.5L). The combined organic layers were washed with water (1.5LX3) and brine (1.5L), dried over magnesium sulfate, filtered and evaporated to give the oil (1.02kg). The oil was purified with silica gel column chromatography [5L, n-hexane (10L), 50% ethyl acetate/n-hexane (30L)] to give the target compound (680g, 95%) as a pale yellow oil. MP : 104.7-105.1°C. 1HNMR (CDC13) : 6 1.45 (3H, s), 4.01(2H, t, J=4Hz), 6.67(1H, s) , 6.8.3(2H, d, J=8Hz), 6.8 7(2H, d, J=8Hz), 7.13(2H, d, J=8Hz), 7.23(2H, d, J=8Hz) . Example 7 4 2-{4-El-(4-Methoxyphenyl)-3-(trifluoromethyl)-lH- pyrazol-5-yl]phenoxy}ethanamine hydrochloride To a solution of hydrogen chloride in ethyl acetate (4N, 1.0L) was added powdered tert-Butyl 2-{4-[1-(4-meth oxyphenyl) -3- (trif luor.omethyl) -lH-pyrazol-5-yl] -phenoxyJethylcarbamate obtained by Example 73 (500g) at 5°C over 2 0min. After stirring at the same temperature for 30min and then at room temperature for lhr, the mixture was evaporated to give oil (543.12g). The oil was dissolved in toluene (1.5L). And then, n-hexane (200ml) and the target compound (as seeds for crystallization) were added to the solution. The mixture was stirred at room temperature overnight. And the precipitate was filtered, washed with toluene (500ml X2) and isopropylether (650ml), and dried to give the target compound (420.5g, 97%) as a white powder. MP : 166.8-168.0°C. 1HNMR (DMSO-d6) : 6 3.185(2H, t, J=5Hz), 3.8(3H, s) , 4. 215(2Hf tf J=5Hz), 6.96-7.05(4H, m) , 7.1(1H, s) , 7.22-7. 33(4H, m). Example 7 5 N-(2-{4-[l-(4-Methoxyphenyl)-3-(trifluoromethyl)-lH- pyrazol-5-yl]phenoxy}ethyl)urea 2-{4-[1-(4-Methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]phenoxy}ethanamine hydrochloride obtained by Example 74 (400g) and sodium acetate (159g) was dissolved in a mixture of N,N-dimethylformamide (1.4L) and water (0.52L) at 50°C. A solution of potassium cyanate (157g) in water (520ml) was added dropwise to the solution over 15min at 38-40°C. The whole solution was stirred at 50°C for 2hrs. The solution was filtered and washed with N,N-dimethylformamide (0.68L) at the same temperature. The filtrate was cooled to room temperature, and then water (0.4L) and the target compound (A04 type crystal) was added as seeds for crystallization to the filtrate, and the mixture was stirred at room temperature for 30min. Then water (2.76L) was added dropwise to the mixture over 30min, and the mixture was stirred at room temperature for 30min. The precipitate was filtered, washed with water (0.8LX3) , and dried under reduced pressure at 45°C overnight to give the target compound (A04 type crystals, 442.Olg) as a white powder. IHNMR (CDCI3) : 8 3.555(2H/ dt, J=5, 6Hz), 3.81(3H, s), 3.995(2H, t, J=5Hz), 4.67 (2H, s) , 5.37(IH, t, J=6Hz), 6.66(1H, br-s), 6.79(2H, d, J=8Hz), 6.845(2H, d, J=6Hz), 7.11(2H, d, J=8Hz), 7.19(2H, d, J=8Hz). IHNMR (DMS0-d6) : Example 7 6 2-Hydroxy-N-{4-[1-(4-methoxyphenyl)-3-(trifluoromethyl) -lH-pyrazol-5-yl]benzyl}acetamide To a solution of 4-[1-(4-methoxyphenyl)-3-(tri-f luoromethyl) -lH-pyrazol-5-yl] benzylamine hydrochloride obtained by Example 57 (46.5mg) in dichloromethane (1.5ml) was added diisopropylethylamine (135//L) and acetoxyacetylchloride (41.6/iL) at 0°C. After stirring at room temperature for 3hrs, the mixture was quenched with water. The whole mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, filtered and evaporated to give oil (67mg). The oil was dissolved in methanol (1.5ml). Potassium carbonate (55mg) was added to the solution. After stirring at room temperature for 3hrs, the mixture was filtered and evaporated to give oil which was purified with preparative thin layer chromatography (0.5mmX2, 10% methanol/chloroform) to give colorless oil (42.5mg). The oil was crystallized from a mixture of ethyl acetate, diisopropylether, and n-hexane with stirring at room temperature. The precipitate was filtered and dried to give the target compound (33.9mg, 64.8%) as a white powder. 1HNMR (CDCI3) : 8 2.32(1H, t, J=5.2Hz), 3.83(3H, s), 4.2 0(2H, d, J=5.2Hz), 4.51(2H, d, J=6.1Hz), 6.72(1H, s) , 6. 87(2H, d, J=8.9Hz), 7 .16-7 . 24 ( 6H, m) . MS (ESI+) : 428.2(M+Na). Example 77 2- Hydroxy-N-(2-{4-[1-(4-methoxyphenyl)-3-(trifluoro- methyl)-lH-pyrazol-5-yl]phenyl}ethyl)ethanesulfonamide To a solution of 2-{4-[1-(4-methoxyphenyl)-3-(trifluoromethyl)-lH-pyrazol-5-yl]phenyl}ethanamine hydrochloride and triethylamine in chloroform was added methanesulfonyl chloride at room temperature. After stirring for Ihr, the reaction mixture was poured into water and chloroform. The aqueous layer was separated and extracted with chloroform. The combined organic layer was washed with water and brine, dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel and crystallized to give the target compound (27.7mg, 23.5%). 1HNMR (CDCI3) : d 2.78-2.91 (2H, m) , 3.16(2H, t, J=5.1Hz), 3.32-3.43(2H, m) , 3.82 (3H, s) , 3.96(2H, t, J=5.1Hz), 4.65 (1H, t, J=6.2Hz) , 6.72(1H, s), 6.87(2H, d, J-9.0Hz) , 7 .12-7.27 (6H, m) . MS(LC, ESI + ) , 4 70.2KMH+) , 511.17 (MHMeCN) . Example 78-1 tert-Butyl 2- (4-acetylphenoxy)ethylcarbamate To a solution of 4-hydroxyacetophenone (lOg) and 2-tert-butoxycarbonylaminoethylbromide (24.7g) in N/N-dimethylformamide (50 ml) was added potassium iodide (12.2g) and potassium carbonate (15.2g). After stirring at 50°C overnight, the mixture was quenched with water and extracted with ethyl acetate (3 times). The combined organic layers were washed with IN sodium hydroxide aqueous solution (2 times) and brine, dried over magnesium sulfate, and evaporated to give oil. The oil was purified with silica gel column chromatography [500ml, 20% ethyl acetate/n-hexane (1000ml), 30% ethyl acetate/n-hexane (1000ml)] to give the target compound (19.89g, 96.9%) as a white solid. 1HNMR(CDC13) : 6 1.46(9H, s), 2.56(3H, s) , 3.52-3.60(2H, ■m), 4.09(2H, t, J=5.1Hz), 6.93(2H, d, J=8.9Hz), 7.93(2H, d, J=8.9Hz). MS (ESI+) : 280.09(MH+). Example 78-2 tert-Butyl 2-[4-(4,4,4-trifluoro-3-oxobutanoyl)- phenoxy]ethylcarbamate A mixture of tert-butyl 2-(4-acetylphenoxy)ethyl¬carbamate obtained by Example 78-1 (15g), trifluoroacetic acid (8.95ml), and sodiumethoxide (8.77g) inethanol (45ml) was stirred at 70°C for 2.5hrs. The mixture was poured into a mixture of aqueous hydrogen chloride solution (IN) and ethyl acetate. The whole mixture was extracted with ethyl acetate (2 times). The organic layer was separated, washed with saturated sodium hydrogencarbonate and brine, dried over magnesium sulfate, and evaporated to give oil (25g) . The oil was purified with silica gel column chromatography [500ml, 30% ethyl acetate/n-hexane (1000ml)] to give oil. The oil was dissolved in ethyl acetate (5ml) under heating by water bath. n-Hexane (100ml) was added to the solution, and the solution was cooled to room temperature over 30min under stirring. And n-hexane (100ml) was added to the mixture. The precipitate was filtered and dried to give the target compound (15.956g, 79.2%) as an orange powder. 1HNMR (CDC13) : d 3.40-3.70(2H, m), 4.00-4.20(2H, m), 5.00(1H, br-s), 6.50(1H, s) , 6.98(2H, d, J=8.6Hz), 7.93(2H, d, J=8.6Hz). Example 78-3 tert-Butyl 2-{4-[1-(4-methoxyphenyl)-3-(trifluoro- methyl)-lH-pyrazol-5-yl]phenoxyjethylcarbamate To a suspension of 4-methoxyaniline (lOOmg) inamixture of acetic acid (2ml) and concentrated hydrogen chloride (0.4ml) was added dropwise a solution of sodium nitrite (61.6mg) in water (0.1ml) over 5min at 3°C, and the mixture was stirred at 3°C for lhr. To the mixture was added dropwise a solution of tin chloride (641mg) in concentrated hydrogen chloride (0.3ml) at 0°C over lOmin, and then the mixture was stirred at 0°C for lhr. Acetic acid (5ml) was added dropwise to the mixture at between -20 and -lO't over 2min, and then the mixture was quenched with a solution of sodium hydroxide (336mg) in water (2.24ml) at -10°C over 2min and warmed to room temperature to give a solution containing 4-methoxyphenylhydrazine hydrochloride. A solution of tert-butyl 2-[4-(4,4,4-trifluoro-3-oxobutanoyl)-phenoxy]ethylcarbamate obtained by Example 78-2 (305mg) was added to the former solution at -10°C, and then the mixture was stirred at room temperature for 3hrs. The mixture was poured into a mixture of saturated sodium hydrogen carbonate aqueous solution (150ml) and ethyl acetate (100ml), and adjusted pH to basic by sodium hydrogencarbonate powder. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (50mlX2) . The combined organic layers were washed with saturated sodium hydrogen carbonate aqueous solution and brine, dried over magnesium sulfate, filtered, and evaporated to give oil (450 mg). The oil was purified with silica gel column chromatography [35 ml, 15% ethyl acetate/n-hexane (800 ml)] to give an oil. (343.2mg, 88.5%). The oil was dissolved in isopropylether (2ml), and then n-hexane (6ml) was added to the solution. The whole mixture was stirred at room temperature for lhr. And then the precipitate was filtered, washed with n-hexane (10ml), and dried under reduced pressure for 2hrs to give the target compound (280.6 mg, 72.4%) as a white powder. 1HNMR (CDCI3) data was identical to authentic sample. 1HNMR (CDCI3) : d 1.45(3H, s), 3.53(2H, dt, J=4.4Hz), 3.82(3H, s), 4.01(2H, t, J=4Hz), 6.67(1H, s) , 6.83(2H, d, J=8Hz), 6.87(2H, d, J=8Hz), 7.13(2H, d, J=8Hz), 7.23(2H, d, J=8Hz). Example 79-1 1-[4-(Benzyloxy)phenyl]hydrazine hydrochloride To the suspension of 4-benzyloxyaniline (lOg) in concentrated hydrogen chloride (100ml) was added dropwise a solution of sodium nitrite (3.2g) in water (10ml) over lOmin at between -15 and -10°C, and then the mixture was stirred at 3°C for lhr. To the mixture was added dropwise a solution of tin chloride (33. 5g) in concentrated hydrogen chloride (80ml) at between -20 and -10°C over 30min, and then the mixture stirred at 0°C for lhr. After cooling to -20°C, the precipitate was filtered, washed with water (25ml), ethanol (25ml) and ether (50ml), and dried to give the target compound (10.637g, 100%) as a pale brown powder. NMR(DMSO-d6) : Example 79-2 2-{4-[l-(4-Benzyloxyphenyl)-3-(trifluoromethyl)-1H- pyrazol-5-yl]phenoxyl}ethanamine hydrochloride The title compound (12.9g, 87.5%) was prepared from 1-[4-(benzyloxy)phenyl]hydrazine hydrochloride obtained by Example 79-1 and tert-butyl 2-[4-(4,4,4-trifluoro-3-oxobutanoyl)phenoxy]ethylcarbamate obtained by Example 78-2 in a similar manner to that of Example 78-3. 1HNMR (DMSO-d6) : 6 3.10-3. 30 (2H, m) , 4.19(2H, t, J=6.3Hz) , 5.14(2H, s), 6.98(2H, d, J=8.7Hz), 7.09(1H, s) , 7.09(2H, d, J=8.9Hz), 7.49-7.22(9H, m). Example 80 N- (2-{4-[l-[4-(Benzyloxy)phenyl]-3-(trifluoromethyl)- lH-pyrazol-5-yl]phenoxy}ethyl)urea The title compound (10.57g, 84.3%) was prepared from 2-{4-[1-(4-benzyloxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]phenoxyl}-ethanamine hydrochloride obtained by Example 79-2 in a similar manner to that of Example 75. 1HNMR (CDC13) : 6 3.57(2H, td, J=5.7, 5.0Hz), 4.01(2H, t, J=5.0Hz), 4.57 (1H, br-s), 5.06(2H, s) , 5.20 (1H, t, J=5.7Hz) , 6.66(1H, s), 6.80(2H, d, J=8.7Hz), 6.93(2H, d, J=9.0Hz), 7.12(2H, df J=8.7Hz), 7.21(2H, d, J=9.0Hz), 7.35-7.42(5H, m) . Example 81 N-(2-{4-[1-(4-Hydroxyphenyl)-3-(trifluoromethyl)-1H- pyrazol-5-yl]-phenoxy}ethyl)urea To a solution of N-(2-{4-[1-[4-(benzyloxy)phenyl]-3-(trifluoromethyl)-lH-pyrazol-5-yl]phenoxy}ethyl)urea obtained by Example 80 (10.33g) in methanol (100ml) was added palladium on carbon (10% wet, 2g) , and the mixture was stirred vigorously at room temperature under hydrogen atmosphere for 3hrs. The whole mixture was fil tered and evaporated to give oil (8.23g) . The oil was purified with silica gel column chromatography [250ml, 3% methanol/chloroform (500ml), 5% methanol/chloroform (500ml), and 10% methanol/chloroform (500ml)] to give the target compound (8.07g, 95.4%) as an oil. 1HNMR (DMSO-d6) : 6 3.28-3.33(2H, m), 3.94(2H, t, J=5.5 Hz), 5.52(2H, br-s), 6.14(1H, br-t, J=5.7Hz), 6.80(2H, d, J=8.7Hz), 6.93(2H, d, J=8.9Hz), 7.05(1H, s), 7.14(2H, d, J=8.7Hz), 7.19(2H, d, J=8.9Hz). MS (ESI+) : 407.10(MH+). Example 82 4-[5-(4-{2-t(Aminocarbonyl)amino]ethoxy}phenyl)-3- (trifluoromethyl)-lH-pyrazol-1-yl]phenyl acetate To a mixture of N-(2-{4-[1-(4-hydroxyphenyl)-3-(trifluoromethyl)-lH-pyrazol-5-yl]phenoxy}ethyl)urea obtained by Example 81 (148.5mg) in dichloromethane (1.5 ml) was added pyridine (163]iL) and acetic anhydride (45y L) , and the mixture was stirred at room temperature for lhr and stirred under reflux for 3hrs. After evaporation, the mixture was purified with preparative thin layer chromatography (1.Omm, 10% methanol/chlorof orm) to give oil. The oil was crystallized from a mixture of dichloromethane and isopropylether at room temperature to give the target compound (138-6mg, 84.6%) as a white powder. 1HNMR (CDC13) : 6 2.30(3H, s) , 3.59(2H, td, J=5.5, 4 . 9H z), 4.04(2H, t, J=4.9Hz), 4.51(2H, br-s), 5.22(1H, br-t, J=5.5Hz), 6.69(1H, s), 6.84(2H, d, J=8.7Hz)f 7.10(2H, d, J=8.8Hz), 7.14(2H, d, J=8.7Hz), 7.31(2H, d, J=8.9Hz). MS(LC, ESI + ) : 449.24(MH+), (ESI-) 492.5 (M-H+HC02") . Example 83-1 1- (1,3-Benzodioxol-5-yl)hydrazine hydrochloride The title compound (1.811g, quant.) was prepared from 3, 4- (methylenedioxy) aniline in a similar manner to that of Example 79-1. 1HNMR (DMS0-d6) : 6 5.94(2H, s) , 6.53(1H, dd, J=2.2 8.2 Hz), 6.80(1H, s), 6.83(1H, d, J=8.2Hz). MS(LS, ESI + ) : 153.9(MH+) 193.99(MH+CH3CN) . Example 83-2 tert-Butyl 2-{4- [1- (1,3-benzodioxol-5-yl)-3-(trifluoro- methyl)-lH-pyrazol-5-yl]phenoxy}ethylcarbamate The title compound (371.3mg, 56.7%) was prepared from tert-butyl 2-[4-(4,4,4-trifluoro-3-oxobutanoyl)-phenoxy]ethylcarbamate obtained by Example 78-2 and 1-(1,3-benzodioxol-5-yl)hydrazine hydrochloride obtained by Example 83-1 in a similar manner to that of Example 78-3. NMR (CDC13) MA12.048 : Example 84 2-{4-[1-(1,3-Benzodioxol-5-yl)-3-(trifluoromethyl)-1H- pyrazol-5-yl]phenoxyJethanamine The title compound (181.2mg, 61.5%) was prepared from tert-butyl 2-{ 4-[1-(1, 3-benzodioxol-5-yl)-3- (tri-fluoromethyl)-lH-pyrazol-5-yl]phenoxy}ethylcarbamate obtained by Example 83-2 in a similar manner to that of Example 74. 1HNMR (CDCI3) : 6 1.75(9H, s), 3.45-3.60 (2H, m), 4.02(2H, t, J=5.1Hz), 6.02(2H, s) , 6.66-6.88(1H, m) , 7.16(2H, d, J=8.8Hz). MS (LC, ESI+) : 392.09(MH+), 433.16(MHMeCN+). Example 8 5 N- (2-{4- [1- (1,3-Benzodioxol-5-yl) -3-(trifluoromethyl)- lH-pyrazol-5-yl]phenoxy}ethyl)urea The title compound (181.2mg, 90.1%) was prepared from 2-{4-[l-(l,3-benzodioxol-5-yl)-3-(trifluoro¬methyl) -lH-pyrazol-5-yl]phenoxy}ethanamine obtained by Example 84 in a similar manner to that of Example 75. 1HNMR (CDC13) : S 3.6(2H, td, J=5.0, 5.0Hz), 4.045(2H, t, J=5Hz), 4.5(2H, br-s), 5.095(1H, br-t, J=5Hz), 6.01(2H, s), 6.66(1H, s), 6.75-6.86(3H, m) , 6.84(2H, d, J=8Hz), 7.16(2H, d, J=8Hz). MS (LC, ESI+) : 435.08(MH+). Example 86 ' tert-Butyl 2-({4-[l-(4-methoxyphenyl)-3-(trifluoro¬methyl) -lH-pyrazol-5-yl]benzyl}amino)-2-oxoethyl-carbamate A mixture of 4-[1-(4-methoxyphenyl)-3-(trifluoro¬methyl) -lH-pyrazol-5-yl]benzylamine hydrochloride obtained by Example 57, N-tert-butoxycarbonyl-glycine, WSCD and 1-hydroxybenzotriazole hydrate in triethylamine and dichloromethane was stirred at room temperature. After stirring for 15hrs, the reaction mixture was poured onto water and chloroform. The aqueous layer was separated and extracted with chloroform. The combined organic layer was washed with water and brine, dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel and crystallized to give the target compound (93.5mg, 88.9%). 1HNMR (CDCI3) : 8 1.43(9H, s) , 3.82(3H, s) , 3. 82-3. 85 (2H, m) , 4.475(2H, d, J=6Hz), 6.71(1H, s), 6.87(2H, d, J=8Hz), 7.14-7.26(6H, m). MS (ESI+) : 505(MH+). Example 87 2-Amino-N-{4-[1-(4-methoxyphenyl)-3-(trifluoromethyl)- lH-pyrazol-5-yl]benzyl}acetamide hydrochloride The title compound (62.3mg, 82.9%) was prepared from tert-butyl 2-({4-[1-(4-methoxyphenyl)-3-(trifluoro¬methyl) -lH-pyrazol-5-yl]benzyl}amino)-2-oxoethyl-carbamate obtained by Example 86 in a similar manner to that of Example 74. 1HNMR (DMSO-d6) : 6 3.61(2H, s), 3.79(3H, s) , 4.345(2H, d, J=6Hz), 7.005(2H, d, J=10Hz), 7.15(1H, s), 7.22-7.32 (6H, m) , 8.09(2H, br-s), 8.93(1H, br-t, J=6Hz) . MS (ESI + ) : 405.33 (free, MH+) . Example 8 8 N-{4-[1-(4-Methoxyphenyl)-3-(trifluoromethyl)-1H- pyrazol-5-yl]benzyl}acetamide To a solution of 4-[1-(4-methoxyphenyl)-3-(trifluoro¬methyl) -lH-pyrazol-5-yl]benzylamine hydrochloride obtained by Example 57 and triethylamine in dichloromethane was added dropwise acetyl chloride at 0°C. After stirring at room temperature for lhr, the mixture was quenched with saturated sodium hydrogen carbonate aqueous solution and extracted with ethyl acetate (3 times) . The combined organic layers were washed with IN hydrochloric acid, water, and brine, dried over magnesium sulfate, and evaporated to give oil, which was purified with silica gel column chromatography (eluted with 50% ethyl acetate/n-hexane) to give oil. The oil was crystallized from a mixture of ethyl acetate and n-hexane at 50^ to give the target compound (52.2mg, 69,3%) as a solid. 1HNMR (CDC13) : 8 2.04(3H, s), 3.83(3H, s), 4.435(2H, d, J=6Hz), 6.7K1H, s), 6.87(2H, d, J=8Hz) , 7 .15-7 .26 (6H, m) . 1R (KBr) : 1647cm-1. MS (ESI+) : 412.1(M+Na). Example 8 9 N- (2-{4- [1- (4-Methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]-phenyl}ethyl)-l-methyl-lH-imidazole-4-sulfonamide The title compound (72mg, 70.8%) was prepared from 2-{4-[1-(4-methoxyphenyl) -3-(trifluoromethyl)-1H-pyrazol-5-yl]phenyl }ethanamine hydrochloride in a similar manner to that of Example 77. 1HNMR (CDCI3) : 6 2.83(2H, t, J=8Hz), 3.26(2H, dt, J=6H z), 3.75(3H, s), 3.83(3H, s) , 5.005(1H, t, J=6Hz), 6.7(1 H, s), 6.88(2H, d, J=8Hz) , 7.13(4H, s), 7.22(2H, d, J=8H z) , 7.45-7.47(2H, m) . MS (ESI+) : 528.1 (MNa+) . Example 90 N- ( (1R)-2-{4-[l-(4-methoxyphenyl)-3-(trifluoromethyl)- lH-pyrazol-5-yl]phenoxy}-l-methylethyl)urea To a solution of (1R)-2-{4-[1-(4-methoxyphenyl)-3-(trifluoromethyl)-lH-pyrazol-5-yl]phenoxy}-l-methyl-ethanamine hydrochloride in dichloromethane was added triethylamine and trimethylsilyl isocyanate at 0°C. After stirring for 5hrs, the mixture was quenched with water and extracted with dichloromethane. The combined organic layers were washed with brine, dried over magnesium sulfate, and evaporated under'reduced pressure to give oil, which was purified with preparative thin layer chromatography (1mm, ethyl acetate) to give oil. The oil was crystallized from a mixture of isopropyl ether, ethyl acetate, and n-hexane to give the target compound as a white# solid (22.8mg, 88.1%). 1HNMR (CDC13) : 6 1.29(3H, d, J=8Hz) , 3.82(3H, s) , 3.87-3.94(2H, m), 4 . 07-4 .19 (1H, m) , 4.51(2H, s) , 4.87(1H, d, J=8Hz), 6.67(1H, s), 6.8-6.89(4H, m) , 7.12(2H, d, J=8Hz), 7.215(2H, d, J=10Hz). MS (ESI + ) : 435.3 (MH+) , 476.3(MH+MeCN) . Example 91 N- (2-{4- [1- (6-Methoxy-3-pyridinyl)-3-(trifluoromethyl)- lH-pyrazol-5-yl]phenoxy}ethyl)methanesulfonamide The title compound (130mg, 71.8%) was prepared from 2-{4-[l-(6-methoxy-3-pyridinyl)-3-(trifluoromethyl)-1H- pyrazol-5-yl]phenoxy}ethanamine dihydrochloride in a similar manner to that of Example 77. 1HNMR (CDCI3) : 8 3.03 (3H, s) , 3.555 (2H, dt, J=5, 5Hz) , 3.94(3H, s), 4.115(2H, t, J=5Hz), 4.785(1H, br-t, J=5Hz), 6.71(1H, s), 6.76(1H, d, J=8Hz) , 6.85(2H, df J=8Hz) f 1. 16(2H, d, J-8Hz), 7.555(2Hf ddr J==8, 2Hz) , 8.085(1H, d, J=2Hz). MS (ESI + ) : 479.1 (M+Na) + . Example 92 4-[5-(4-Methoxyphenyl)-3-(trifluoromethyl)-IH-pyrazol- 1-yl]phenol A mixture of 4-methoxy-l-(4,4,4-trifluoro-3-oxo-butanoyl)benzene (5.0g) and p-hydroxyphenyl hydrazine hydrochloride (3.59g) in acetic acid (30ml) was stirred at room temperature. After stirring for 15hrs, toluene and water was added. The aqueous layer was separated and extracted twice with toluene. The combined organic layer was washed with water (twice) and brine, dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel to give the target compound (4.88g/ 71.9%) as crystals. 1H NMR (CDCI3) : 8 3.80(3H, s), 6.68(1H, s) , 6.72(2H, d, J=8.8Hz), 6.83(2H, d, J=8.8Hz), 7.12(2H, d, J=8.8Hz), 7.13 (2H, d, J=8.8Hz) . MS (ESI+) : m/z 357 (M+Na). Example 93 2-{4-[5-(4-Methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]phenoxy}ethanol A suspension of 4-[5-(4-methoxyphenyl)-3-(tri-fluoromethyl)-lH-pyrazol-l-yl]phenol obtained by Example 92 (500mg), potassium carbonate (1.24g), potassium iodide (1.49g), and 2-chloro-l-ethanol (0.60m 1) was stirred at 80°C for 5hrs. After cooling, the reaction mixture was poured into water. The mixture was extracted twice with ethyl acetate, washed with water and brine, dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel to give the target compound (545mg, 96.4%). 1H NMR (CDC13) : d 2.03(1H, t, J=5.8Hz), 3.81(3H, s) , 3. 94-4.01(2H, m) , 4.09(2H, dd, J=3.5 ,4.6Hz), 4.52(3H, s) , 6.68(1H, s), 6.84(2H, d, J=8.9Hz), 6.89(2H, d, J=9Hz), 7.13(2H, d, J=8.9Hz), 7.24(2H, d, J=9Hz). MASS (ESI + ) : m/z 401 (M+Na) . Example 94 {4-[5-(4-Methoxyphenyl)-3-(trifluoromethyl)-lH-pyrazol- l-yl]phenoxy}acetonitrile A suspension of 4-[5-(4-methoxyphenyl)-3-(tri-fluoromethyl)-lH-pyrazol-l-yl]phenol obtained by Example 92 (2.0g), potassium carbonate (992mg), potassium iodide (993mg), and chloroacetonitrile (0.57m 1) was stirred at 80°C for 4hrs. After cooling, the reaction mixture was poured into water. The mixture was extracted twice with ethyl acetate, washed with water and brine, dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel to give the target compound (1.75g, 78.3%) as an oil. 1H NMR (CDCI3) : 6 3.81(3H, s), 4.79(2H, s), 6.69(1H, s), 6.86(2H, d, J=8.8Hz), 6,96(2H, d, J=9Hz), 7.14(2H, d, J -8.8Hz), 7.31(2H, d, J=9Hz). MS (APCI+) : m/z 374 (M+l) . Example 95 tert-Butyl 2-{4-[5-(4-methoxyphenyl)-3-(trifluoro- methyl)-lH-pyrazol-1-yl]phenoxy}ethylcarbamate The title compound (420mg, 21%) was prepared from 4- [5-(4-methoxyphenyl)-3-(trifluoromethyl)-lH-pyrazol-1-yl]phenol obtained by Example 92 in a similar manner to that of Example 73. 1H NMR (CDCI3) : 5 1.46(9H, s) , 3.501-3.58 (2H, m) , 4.02 (2H, t, J=5.1Hz), 4.99(1H, br-s), 6.67(1H, s) , 6.84(2H, d, J=8.9Hz), 6.85(2H, d, J=9Hz), 7.13(2H, d, J=8.9Hz), 7. 23 (2H, d, J=9Hz) . MS (ES1+) : m/z 500 (M+Na) . Example 96 2-{4-[5-(4-Methoxyphenyl)-3-(trifluoromethyl)-1H- pyrazol-1-yl]phenoxy}ethanamine hydrochloride The title compound (0.35g, 96.2%) was prepared from tert-butyl 2-{4-[5-(4-methoxyphenyl)-3- (trifluoro¬methyl) -lH-pyrazol-l-yl]phenoxyJethylcarbamate obtained by Example 95 in a similar manner to that of Example 74. 1H NMR (CDC13+CD30D) : 6 3.2-3.5(4H, m) , 3.81(3H, s) , 4. 2-4.35(2H, m), 6.70(1H, s), 6.84(2H, d, J=8.6Hz), 6.95(2 H, d, J=8.6Hz), 7.13(2H/ d, J=8.6Hz), 7.25(2H, d, J=8.6H z) - MS (ESI + ) : m/z 378 (M-Cl) . Example 97 N- (2-{4- [5- (4-Methoxyphenyl)-3-(trifluoromethyl)-1H- pyrazol-1-yl]phenoxy}ethyl)methanesulfonamide To a solution of 2-{4-[5-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-l-yl]phenoxy}ethanamine hydrochloride obtained by Example 96 (lOOmg) in dichloromethane (5ml) and triethylamine (0.1ml) was added dropwise methanesulfonyl chloride (38£ll) at room temperature. After stirring for 2hrsf the reaction mixture was partitioned between chloroform and water. The aqueous layer was extracted with chloroform. The combined organic layer was washed with water and brine, dried over magnesium sulfate, filtered and evaporated under reduced pressure. The residue was purified with high performanced thin layer chromatography to give the target compound (35mg, 31.8%) as crystals. 1H NMR (CDC13) : 6 3.03(3H, s), 3.56(2H, dt, J=5 ,5.7Hz), 3.8M3H, s), 4.11(2H, t, J=5Hz) , 4.82(1H, t, J=5.7Hz), 6.68(1H, s), 6.85(2H, d, J=7.9Hz), 6.85(2H, d, J=8.7Hz), 7.13(2H, d, J-8.7Hz), 7.24(2H, d, J=7.9Hz). MS (ESI + ) : m/z 478 (M+Na) . Example 98 N- (2-{4- [5-(4-Methoxyphenyl)-3-(trifluoromethyl)-1H- pyrazol-1-yl]-phenoxy}ethyl)urea To a solution of 2-{4-[5-(4-methoxyphenyl)-3- (tri-fluoromethyl)-lH-pyrazol-1-yl]phenoxy}ethanamine hydrochloride obtained by Example 96 (200mg) in water (10ml) and ethanol (5ml) was added sodium cyanate (314m g) at room temperature. After stirring for 15hrs, the reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water, dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was column chromatography by high perf ormanced thin layer chromatography (chloroform:methanol=8:1) to giVe the target compound (0.148g, 72.8%). 1H NMR (CDC13) : 8 3.60(2H, dt, J=5.6, 5.0Hz), 3.81(3H, s) , 4.04 (2H, t, J=5.0Hz), 4.50(2H, br-s), 5.12(1H, t, J=5.6Hz), 6.68(1H, s), 6.84(2H, d, J=8.8Hz), 6.85(2H, d, J=8.9Hz), 7.13(2H, d, J=8.8Hz), 7.22(2H, d, J=8.9Hz). MS (ESI+) : m/z 443 (M+Na). Example 99 N- (2-{4- [3-(Difluoromethyl)-1-(4-methoxyphenyl)-1H- pyrazol-5-yl]phenyl}ethyl)-2-hydroxyethanesulfonamide To a solution of 2-(2-{4-[1-(4-methoxyphenyl)-3-difluoromethyl-lH-pyrazol-5-yl]phenyl}ethyl)-1H-isoindole-lf3(2H)-dione in acetonitrile was added hydrazine monohydrate. After stirring at 60°C overnight, the mixture was filtered. And the filtrate was evaporated to give 2-{4-1-(4-methoxyphenyl)-3-(difluoromethyl)-lH-pyrazol-5-rl]phenyl}ethanamine as an orange oil. To a solution of the oil and triethylamine in chloroform /as added 2-hydroxyethanesulfonyl chloride at room ;emperature. After stirring for lhr, the reaction mixture was poured )nto water and chloroform. The aqueous layer was separated md extracted with chloroform. The combined organic layer *as washed with water and brine, dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel and :rystalized to give the target compound (220mg, 76.1%). LH NMR (CDC13) : 8 2.875(2H, t, J=7Hz) , 2. 91-3.19 (2H, m) , 3.395(2H, dt, J=6Hz) , 3.83(3H, s) , 3.985(2H, t, J=5Hz), 3.44(1H, br-t, J=6Hz) , 6.7(1H, s), 6.765(1H, t, J-55Hz) , 5.875(2H, d, J=10Hz).f 7.12(6H, s) . AS (ESI+) : 452.19(MH+). x To a suspension of A1C13 (45. 9g) was added dropwise acetyl -hloride (13.4ml) (About 5°C), and then I (25.7g) mentioned above under ice-cooling (5-10°C) . After stirring for 8 hours, the reaction mixture was poured onto ice-water. The organic layer was separated andwashed with water (twice) andlNHCl, sat.NaHC03 and brine, dried over MgS04, filtered and evaporated under reduced pressure to give crude product. The product was distilled under reduced pressure to give 105.8g (84%) of the following compound (P0001) (P0001) TLC Check: Ninhydrin/UV b.p. 1> 91-117 °C /0.7mmHg. E111271-1 12.6g 2> 117 °C /0.7mmHg. E111271-2 105.8g (P0002) The above compound P0002 was prepared in a similar manner to that of P0001. Mass (API-ES positive) : 243 (M+Na)+ 200MHz 1H NMR (CDC13, d) : 1. 91-2. 05 (2H, m) , 2.06(3H, s), 2.59(3H, s), 2.76(2H, t, J=7.7 Hz) , 4.09(2H, t, J=6.5 Hz), 7.28(2H, d, J=8.2 Hz), 7.90(2H, d, J=8.2 Hz) Preparation 3 (P0003) 60% Sodium hydride 427mg was added to a solution of the compound P0001 (2g) and ethyl trif luoroacetate 2. 6ml in DMF 10ml portionwise (in three portions) under ice bath cooling. The reaction mixture was stirred at same temperature for 45minutes. Then ice bath was replaced to water bath. The temperature of reaction mixture was raised to 24.5°C, then slowly fall down to 22°C over lhour. The mixture was stirred at r.t. for lhour, then poured into a mixture of 1M HC1 12ml and ice 4 0ml. The whole mixture was extracted with AcOEt 20ml. The organic layer was washed with H20 30ml, saturated aqueous sodium chloride solution, dried over magnesium sulfate, concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with toluene. Obtained crystals were washed with chilled n-hexane 10ml and petroleum ether 5ml by decantation to give a compound P0003 as white crystals, mp. 87-88°C Mass (API-ES negative) : 301(M-H)+ 200MHz 1H NMR (DMSO-d6, d) : 3.00 (2H, t, J=6.7 Hz) , 4.27(2H, t, J=6.7 Hz) , 6.99(1H, s) , 7.48 (2H, d, J=8.3 Hz), 8.08(2H, d, J=8.3 Hz) P0004 was prepared in a similar manner to that of P0003 as shown in Preparation 3. Mass (API-ES negative) : 315 (M-H)+ NMR JA2 4.112 200MHz 1H NMR (CDC13, d) : 1. 92-2. 06 (2H, m) , 2.06(3H, s) , 2.7 4-2.82(2H, m) , 4.10 (2H, t, J=6.5Hz) , 6.55QH, s) , 7.33(2H, d, J=8.3 Hz), 7.89(2H, d, J=8.3 Hz) (P0005) P0005 was prepared in a similar manner to that of P0003 as shown in Preparation 3. yellow crystals Mass (API-ES positive) : 259 (M+Na)+ 400MHz 1H NMR (CDC13, d) : 1.4K3H, t, J=7.1 Hz), 4.40(2H, q, J=7. 1 Hz), 6.93(2H, d, J=8.9 Hz), 7.02 (1H, s), 7.96(2H, d, J=8.9 Hz) (P0006) P0006 was obtained according to a similar manner to that of P0003. (PREPARATION 3) ( P0007) 60% Sodium hydride 233mg was added to a solution of P0001 Ig and ethyl pentaf luoropropionate 0 . 93ml in three portions under ice bath cooling. The reaction mixture was stirred at 24-27°C with cooling in a water bath for several hours, then poured into a mixture of ice and 1M HC1 50ml. The whole mixture was extracted with AcOEt twice. The combined organic layer was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo to give P0007 1.94g as an oil. Mass (API-ES negative) : 309 (M-H)+ 2 0 0MHz 1H NMR (CDC13, d) : 2.90-3.05(2H, m) , 3.85-4.00(2H, m) , 6.62(1H, s), 7.39(2H, d, J=8.3 Hz), 7.92(2H, d, J=8.3 Hz) (P0008) 20% solution of sodium ethoxide in EtOH 18ml was added dropwise to a solution ofPOOOl (4.OOg) and diethyl oxalate 5 . 95g in DMF 12ml at 4-6°C. After stirring at same temperature for Ihour, the reaction mixture was poured into a mixture of ice-water 100ml and cone. HC1 5ml, and extracted with AcOEt. The organic layer was washed successively with 1M HC1, H20, and saturated aqueous sodium chloride solution, dried over magnesium sulfate, treated with activated carbon, then filtered through a SiO2(20ml) pad. The pad was washed with AcOEt. The filtrate and combined washings were concentrated in vacuo to give P0008 (6.05g). as an oil. Mass (API-ES positive) : 287(M+Na)+, (API-ES negative) 263(M-H) + 200MHz 1H NMR (CDC13, d) : 1.42(3H, t, J=7.1Hz), 2.96(2H, t, J=6.5Hz), 3.93(2H, t, J=6.5Hz), 4.40(2H, q, J=7.1Hz), 7.06(1H, s), 7.38(2H, d, J=8.3Hz), 7.96(2H, d, J=8.3Hz) u // r O O ( P0009) To a solution of 4-Hydroxybenzophenone (160 g), Ethyl trifluoroacetate (182 ml), and ethanol (11 ml) in N, N-dimethylformamide (670 ml) was addedportionwise sodium hydride (suspension in mineral oil, 103 g) over 15 minutes at 0 ~ 35°C. The mixture was stirring at room temperature for 2 hours, and then at 35 ~ 40°C for 3 hours. The mixture was poured into a mixture of ice and concentrated hydrogen chloride (320 ml) (aqueous layer total 4L) and diisopropyl ether (2 L) . The aqueous layer was separated and extracted with diisopropyl ether (500 ml x 2). The combined organic layers were washed with water (500 ml x 4) and brine, dried over magnesium sulfate, and evaporated to give 415 g of solid. The solid was dissolved in diisopropyl ether (200 ml) at 65°C. The solution was added dropwise hexane (1.5 L) under stirring at room temperature. After stirring at room temperature for 1 hour, The suspension was filtered and dried under reduced pressure to give solid (first crop, 109.53 g, 40%). The mother liquid evaporated and similarly treated diisopropyl ether (20 ml) and hexane (250 ml) to give second crop (71.11 g, 26%). P0009 (first corp and second corp total, 66.2%). NMR(CDC13); 5.65(1H, brs), 6.50(1H, s) , 6.94(2H, d, J=8.8 Hz), 7.91(2H, d, J=8.8 Hz). MS(ESI+), 255.1(M+Na)+. (P0010) This compound was obtained according to a similar manner to that of P0009 (S0203744) as a powder (56.195 g, 102%). NMR(CDC13); 6.01(1H, t, J=54 Hz), 6.49(1H, s), 6.92(2H, d, J=8.8 Hz), 7.90(2H, d, J=8. 8 Hz). MS(ESI-), 213.3(M-H)+ ( POOH) A mixture of P0009 (100 g), 4-Methoxyphenylhydrazine hydrochloride (82 .4 g) , and sodium acetate (42 . 6 g) in acetic acid (550 ml) was stirring at 70°C for 3 hours. After cooling to room temperature, the mixture was poured into water (4 L) and stirred at room temperature for 1 hour. The precipitate was filtered, washed with water (250 ml x 3) and Hex (500 ml x 2)> and dried at room temperature overnight to give powder (157.86 g) . The powder was purified by recrystallization from ethyl acetate andhexane to give POOH as a powder 121.34G (77%). NMR(CDC13); 3.82 (3H, s) , 5.08(1H, brs) , 6.67(1H, s) , 6.77(2H, d, J=8.6 Hz) , 6.87(2H, d, J=9.0 Hz) , 7.09(2H, d, J=8.6 Hz) , 7.23 (2H, d, J=9.0 Hz) . MS(ESI+); 357.1(M+Na)+. ( P0012) This compound was obtained according to a similar manner to that of P0011 as a solid (3.2028 g, 72%). NMR(DMSO-d6) ; 3.88(3H, s) , 6.74(2H, d, J=8.6Hz), 6.82(1H, s), 6.90(1H, d, J=8.6Hz), 7.10(2H, d, J=8.6Hz), 7.09(1H, t, J=55 Hz) , 7.68(1H, dd, J=8.6, 2.7 Hz), 8.12(1H, d, J=2.7 Hz) . MS(ESI+); 316.1(M-H)+, 633.3(2M-H). Preparation 13 / CI (P0013) This compound was obtained according to a similar manner to that of POOH. (P0014) To a solution of 4-methoxyphenylhydrazine hydrochloride (3.43 g) in water (7.7 ml) was added a solution of P0009 in acetic acid (50 ml) . The mixture was then allowed to stand at room temperature overnight. The mixture was poured into water (500 ml) and stirred at room temperature for 1 hour. The precipitate was filtered, washed with water (100 ml), and dried at room temperature to give P0014 as a brown solid (3.26 g, 90%). NMR(DMSO-d6); 3.88(3H, s) , 6.75(2H, d, J=8.6Hz), 6.92(1H, d, J=8.5 Hz) , 7. 06-7.15 (3H, m) , 7.7 3 (1H, dd, J=8.5, 2.8 Hz) , 8.16(1H, d, J=2.8 Hz), 9.86(1H, s, OH). MS(ESI-); 334.1(M-H)+, 669.2(2M-1)+. Preparation 15 (P0015) This compound was obtained according to a similar manner to that of P0014 as a pale brown powder (13.58 g, 91.7%). NMR(DMS0-d6); 3.94(3H, s), 6.67(1H, s), 6.75(1H, t, J=55 Hz), 6.73-6.80(3H, m) , 7.09(2H, d, J=8.6Hz), 7.57(1H, dd, J=8.6, 2.6 Hz), 8.07(1H, d, J=2.6 Hz). MS(ESI-); 316.KM-H), 633.3 (2M-H) . (P0016) (P0016-1) 1M NaOH 1ml was added to a solution of P0016-1 (reported inW09427973) 1. 31gandinEtOH 5ml andthemixturewas stirred at amibient temperature overnight. The mixture partitioned between AcOEt and H20. The organic layer was washed with H20, saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with AcOEt / n-hexane to give P0016 (900mg) as an oil. Mass (ESI+) : 331 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : -0.05(6H, s), 0.82(9H, s), 0.94(4H, d, J=6.0Hz), 2.38-2.52(1H, m) , 2.78(2H, t, J=6.6 Hz), 3.79(2H, t, J=6.6Hz), 7.01(1H, d, J=16.2Hz), 7.29(2H, d, J=8.1 Hz) , 7.65(2H, d, J=8.1 Hz) , 7.65(1H, d, J=16.2 Hz) 6 (P0017) P0017 6.41gwas prepared in a similar manner to that of P0016. Mass (API-ES positive) : 255 (M+Na) + 200MHz 1H NMR (CDC13, d) : 0.90-1.01(2H, m) , 1.11-1.20(2H, m) , 2.22(1H, m) , 3.49(3H, s) , 5.21(2H, s) , 6.78(1H, d, J=16.0 Hz) , 7.05(2H, d, J=8.7 Hz) , 7.52 (2H, d, J=8.7 Hz) , 7.58(1H, d, J=16.0 Hz) (P0018) 30% H202 0 . 64ml and 3MNaOH 0 . 64ml was added to a 0 . 25M solution of, P0016 1. 03g in EtOH: acetone=3 :1. The mixture was stirred at ambient temperature overnight. The mixture was concentrated in vacuo, and partitioned between AcOEt and H20. The organic layer was washed withH20, saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo to give P0018 (792mg) as an oil. Mass (ESI+) : 347 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : -0.05(6H, s), 0.82(9H, s) , 0.92-1.04(4H, m) , 2.24(1H, m), 2.75(2H, t, J=6.7 Hz), 3.76(2H, t, J=6.7Hz), 3.86(1H, d, J=1.9 Hz), 4.19(1H, d, J=1.9 Hz), 7.24(2H, d, J=8.4 Hz), 7.30(2H, d, J=8.4 Hz) (P0019) P0019 1. 082g was prepared from POO 17 1. Og in a similar manner to that of P0018. Mass (API-ES positive) : 271(M+Na)+ 200MHz 1H NMR (DMSO-cl6, d) : 0.90-1.04 (4H, m) , 2.24 (1H, m) , 3.37(3H, s), 3.88(1H, d, J=1.9Hz), 4.17(1H, d, J=L9Hz), 5.20(2H, s), 7.03(2H, d, J=8.7 Hz), 7.32(2H, d, J=8.7 Hz) 200MHz 1HNMR (CDC13, d) : 0 . 90-1. 07 (2H, m) , 1 -12-1. 2 6 (2H, m) , 2.18(1H, m) , 3.48 (3H, s) , 3.58 (1H, d, J=1.9Hz) , 4.05 (1H, d, J=1.9Hz), 5.18(2H, s) , 7.04(2H, d, J=8.7Hz), 7.23(2Hf d, J=8.7 Hz) (P0020) . . P0005 17.00g was dissolved in warm EtOH 68ml and AcOH 170ml at 70°C. To this solution was added P0005, suspended in H20 20ml, in one portion. The mixture was stirred at 70°C for 1.5hours and then poured into a mixture of ice 500ml and conc.HCl 10ml. Diisopropyl ether 100ml was added and the mixture was stirred at ambient temperature for 20minutes. The precipitates were collected and washed successively with 1M HC1, H20, and diisopropylether. This was air dried overnight to give P0020 21.28g was a pale yellow powder. Mass (ESI+) : 339 (M+H)+ 400MHz 1H NMR (CDC13, d) : 1.41(3H, t, J=7.1 Hz), 3.82(3H, s), 4.44(2H, q, J=7.1Hz), 6.76(2H, d, J=8.7Hz), 6.85(2H, d, J=9.0Hz), 6.96(1H, s), 7.08(2H; d, J=8.7Hz), 7.24(2H, d, J=9.0 Hz) -O' ! (P0021) P0021 was prepared from P0005 in a similar manner to that of P0020. white powder Mass (ESI+) : 340 (M+H)+ 200MHz 1H NMR (DMS0-d6, d) : 1.31(3H, t, J=7.1 Hz) , 3.88(3H, s) , 4.32(2H, q, J=7 .1 Hz) , 6.74 (2H, d, J=8 . 6 Hz) , 6.92(1H, d, J=8.8 Hz), 7.00(1H, s) , 7.09(2H, d, J=8.6 Hz), 7.71(1H, dd, J=8.8,2.7 Hz), 8.13(1H, d, J=2.7 Hz), 9.82(1H, s) (P0022) A solution of triphenylphosphine 831mg in THF 5ml was added dropwise to a solution of E0118 521.8mg and carbon tetrabromide 1.15g in THF 5ml at ambient temperature. The reacionmixturewas stirredat ambient temperaturer for lhour. Carbon tetrabromide 573mg and triphenylphosphine 415mg were added in one portion and stirred for further lhour. Unsoluble matter was filtered off and washed with THF. The filtrate and combined washings were concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with AcOEt / n-hexane = 5%, then 25% to give P0022 647.2mg as pale yellow wax. mp.60-70°C Mass (API-ES positive) : 425,427 (M+H)+ , 447,449(M+Na)+ 200MHz 1H NMR (CDC13, d) : 3.12-3.19(2H, m) , 3.52-3.60(2H, m), 3.82(3H, s) , 6.72(1H, s), 6.87(2H, d, J=9.0Hz), 7.16-7.30(6H, m) (P0023) P0023 was prepared in a similar manner to that of P0022. colorless oil Mass (API-ES positive) : 448,450 (M+Na)+ 4 00MHz 1H NMR (DMSO-d6, d) : 3.14(2H, tf J=7.2 Hz) , 3.7 4(2H, t, J=7.2 Hz), 3.88(3H, s) , 6.92(1H, d, J=8.8 Hz), 7.20(1H, s)7 7.27(2Hf d, J=8.4 Hz), 7.32(2H, d, J=8.4 Hz), 7.76(1H, dd, J=2.7,8.8 Hz), 8.19(1H, d, J=2.7 Hz), Preparation 24 To a solution of P0001 (20.Og) and P0024-0 (53.4g) in DMF (200ml) was added portionwise NaH (4.27g) under ice-cooling. The reaction mixture was warmed at room temperature and the temperature was kept under 4 0°C. After stirring for 5 hours, the reaction mixture was poured onto ice-cooled dilHCl and extracted twise with ethylacetate. The combined organic layer was washed with water (twice) and brine, dried over MgS04, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel (500ml, Hex:EtOAc) to give 12.12g of P0024 as crystal, mp: 52.6-53.6°C / o (E0100) To a solution of 4-hydroxybenzophenone (4.16g) and chloromethyl methyl ether (2.4 6g) in N, N-dimethylacetoamide (15ml) was added portionwise sodium hydride (suspension in mineral oil (60%), 1.22g) over 15 minutes at 0 °C. The mixture was stirred for 30 minutes at ambient temperature. To the reaction mixture was added 2-propanole (0.5ml) , carbon disulfide (2.56g) and portionwise sodium hydride (suspension in mineral oil (60%) , 2.50g) over 15 minutes at 25D. The mixture was stirred at ambient temperature for 1.5 hours,diluted with toluene (20ml) and poured into a mixture of ice and concentrated hydrogen chloride (8 ml) (aqueous layer total 68ml). The resultant mixture was extracted with ethyl acetate , washed with brine,dried over magnesium sulfate, and evaporated. To the mixture of the.resultant residue and sodium hydrogen carbonate (13g) in ethyl acetate (30ml) and water (20ml) was added portionwise the solution of iodine (3.88g) and sodium iodide (8.0g) in water at 0°C. To the mixture was added portionwise 4-Methoxyphenylhydrazine hydrochloride (3-80g) at 0°C under nitrogen. The mixture was stirred at ambient temperature for 3 hours and the organic layer was seperated, washed with water and brine, dried over magnesium sulfate, and evaporated. To the solution of the residue in ethyl acetate (30ml) was added methyl iodide (4.0ml) and triethylamine (10ml) at 0°C. The mixture was stirred for 30 minutes at ambient temperature, washed with water and aqueous potassium carbonate, dried over magnesium sulfate, and evaporated. The residue was column chromatographed on silica gel (80g) ,eluting with a mixture of ethyl acetate and toluene (1:20) to give 7 . 56g of 5-[4-(methoxymethoxy)- phenyl]-1-(4-methoxyphenyl)-3-(methylthio)-IH-pyrazole. To the solution of methyl sulfide (7.56g) in dichloromethane (30 ml) was added a solution of m-chloroperbenzoic acid (80%,4.4g) in dichloromethane (15ml) at 0°C, and the mixture was stirred at 0°C for 1 hour. The mixture was washed with aqueous potassium carbonate , dried over magnesium sulfate, and evaporated. The residue was column chromatographed on silica gel (80g) ,elutingwith ethyl acetate to give 5.43g of 5-[4-(methoxymethoxy)phenyl]-1-(4-methoxyphenyl)-3-(methylsulfinyl)-lH-pyrazole (E0100). mp.136.9-137.3°C Mass;373(M+l) IR(KBr);1054cm-l NMR(CDC13,5) ;3.00(H, s) , 3.48(H, s) , 3.83(H, s) , 5.17(H, s), 6.88(H, d, J=9.0Hz), 6.92(H, s) , 6.97(H, d, J=8.8Hz), 7.14(H, d, J=8.8 Hz), 7.22(H, d, J=9.0 Hz), / 0 (E0101) To the solution of 5-[4-(methoxymethoxy)phenyl]-1-(4-methoxyphenyl)-3-(methylsulfinyl)-lH-pyrazole (7.56g) in dichloromethane (20 ml) was added m-chloroperbenzoic acid (60%,3.76g) at 0°C, and the mixture was stirred at 0°C for 3 hour. The mixture was washed with aqueous sodium hydrogen carbonate , dried over magnesium sulfate, and evaporated. The residue was purified by recrystallization with toluene to give 5.07g of 5-[4-(methoxymethoxy)phenyl]-1-(4-methoxyphenyl)-3-(methylsulfonyl)-lH-pyrazole(E0101) . mp.128.0-128.1°C Mass;389(M+l) IR(KBr);1300cm-l NMR(CDC13,5) ;.3.29(3H, s) , 3.4 8 (3H, s) , 3.83(3H, s) , 5.17(2H, s), 6.88(2H, d, J=9.0 Hz), 6.93(1H, s) , 6.98(2H, d, J=8.8 Hz), 7.13(2H, d, J=8.8 Hz), 7.24(2H, -d, J=9.0 Hz), (P0024) To the solution of 5-[4-(methoxymethoxy)phenyl]-1-(4-methoxyphenyl)- 3-(methylsulfonyl)-lH-pyrazole (0.93g) in a mixture of tetrahydrofuran (10ml) andisopropylalcohol (5ml) was added hydrogen chloride aqueous solution (20%,8ml) at ambient temperature. The solution was stirred for 3 hours, extracted with ethyl acetate , washed with brine, dried over magnesium sulfate,and evaporated to give 0.82g of 4-[1-(4-methoxyphenyl)-3-(methylsulfonyl)-lH-pyrazol- 5-yl]phenol (P0025). Mass;345(M+l) NMR(DMSO-d6,5);3.32(3H, s) , 3.7 9 (3H, s) , 6.73 (2H, d, J=8.6 Hz), 7.01(2H, d, J=8.9Hz), 7.05(1H, s), 7.08(2H, d, J=8.6 Hz), 7.27(2H, d, J=8. 9 Hz), 9.84(1H, s), To a solution of P0026-0 (5.0g) and imidazole (3.3g) in DMF (40ml) was added portionwise TBDMSC1 (6.69g) at room temperature. After stirring overnight, water and hexane was added. The aqueous layer was separated and extracted twice with hexane. The combined organic layer was washed with water (twice) and brinef dried over MgS04f filtered and evaporated under reduced pressure to give 9. 49g (98.3%) of P0026. IR (film): 2952.5, 2935.1, 1467.6, 1255.4, 1124.3, 1097.3, 838.9, 777.2 cm~l. (P0027-0) (P0027) To a solution of P0027-0 (lOg) and dimethylcarbonate 5.97g in DMF was added sodium methoxide 4.77g. The mixture was stirred at ambient temperature for 2hours. The mixture was poured into water with 8 ml of cone. HC1, and extracted with AcOEt. The organic layer was dried over magnesium sulfate, and concentrated in vacuo. The residue was purif iedby silica gel column chromatography to give orange solid. Which was recrystallized from MeOH to give P0027 as white crystals. NMR (200 MHz, CDC13) 3.75(3H, s) , 3.96(2H, s) , 5.14(2H, s) , 7.02(2H, d, J=8.9 Hz) , 7.34-7.45(5H, m) , 7.93(2H, df J-8.9 Hz) Mass ESI 285(M+H)+ (file platform 7366-1) (P0028) To a solution of triphenylphosphin oxide 294mg in 1,2-dichloroethane 3ml was added trifluoromethanesulfonic anhydride 198mg dropwise under cooling in an ice bath. The mixture was stirred at same temperature for 15minutes, when white precipitates were came out. To this mixture was added P0027 (300mg) in 1, 2-dichloroethane 2ml dropwise, followed by addition of Et3N 214mg. The mixture was re fluxed for 2hours -The mixture was allowed to cool to ambient temperature and was washed with H20, sat.aq NaCl, dried over MgS04, concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with AcOEt / n-hexane = 5%, and 10%. The residue was crystallized from IPE to give P0028 (166mg) as a white powder. Mass (ESI+) : 289 (M+Na)+ 200MHz 1HNMR (DMSO-d6, d) : 3.7 6(3H, s) , 5.18 (2H, s) , 7.11(2H, d, J=8.8Hz), 7.33-7.48(5H, m), 7.62(2H, d, J-8.8 Hz) (P0029) Solid KOH 124mg was dissolved in EtOH 5ml at 50°C. To this solution was added P0028 (196mg). After stirring at same temperature for 2hours, the reaction mixture was allowed to cool to ambient temperature. The mixture was partitioned between 1M HC1 and CHC13. The aqueous layer was reextracted with CHC13 . The combined organic layers were dried over MgS04, evaporated in vacuo. The residual crystals were collected and washed with IPE to give 1st crop of P0029 (87mg) as a white powder. The mother liqour was concentrated in vacuo and the residual crystals were collected and washed with n-hexane to give 2nd crop of P0029 (39mg) as a slightly reddish powder. Mass (ESI-) : 251 (M-H) + 200MHz 1H NMR (CDC13, d) : 5.10(3H, s), 6.97(2H, d, J=8.9 Hz), 7.34-7.43(5H, m) , 7.56(2H, d, J=8.9 Hz) (P0030-0) (P0030) To a solution of P0030-0 (2g) and triethylphosphonoacetate 2.32g in DMF 20ml was added 60% NaH 4 90mg in two portions with cooling on ice bath. The mixture was stirred at same temperature for lhour, and then poured into ice water containing NH4C1. The mixture was stirred for a while, and white precipitates were collected and washed with water and 10% aqueous IPA to give P0030. 200MHz 1H NMR (CDC13, d) : 1.33(3H, t, J=7.2 Hz) , 4.25(2H, q, J=7.2 Hz) , 5.10 (2H, s) , 6.31(1H, d, J=16.0 Hz) , 6.97(2H, d, J=8.7 Hz), 7.32-7.50(7H, m), 7.64(1H, d, J=16.0 Hz) Toasolutionof P0030 (2.79g) inCH2C12 28ml was addedbromine 1.66g dropwise under ice bath cooling. The mixture was stirred at same temperature for 30minutes. The reaction mixture was poured into 5% aqueous solution of Na2S203, and partitioned. The organic layer was washed with sat. aqNaHC03, sat.aqNaCl, dried over MgS04, concentrated in vacuo. The residual crystals were collected and washed with n-hexane to give P0031 (3.07g) as a pale yellow powder. 200MHz 1H NMR (CDC13, d) : 1.38(3H, t, J=7.2 Hz), 4.35(2H, q, J=7.2 Hz) , 4.81 (1H, d, J=11.8 Hz) , 5.07 (2H, s) , 5.35(1H, d, J=11.8 Hz) , 6.98 (2H, d, J=8 .7 Hz) , 7.34 (2H, d, J=8.7 Hz) , 7.32-7.45(5H, m) 85% solid KOH 1.73g was dissolved in 95% aqueous EtOH 20ml at50°C. P0031 (3.05g) was added in one portion and the mixture was ref luxed for 9hours. To this mixture was added a solution of 85% KOH 0.32g dissolved in 95% aqueous EtOH 10ml and ref luxed for 5hours. The mixture was cooled in an ice bath, precipitates were collected and washed with EtOH. The crystals were suspended in AcOEt and H20, cooled in an ice bath, acidified by 3M HC1 and 1M HC1. The mixture was partitioned and the organic layer was washed with H20, dried over MgS04, concentrated in vacuo. The residual solid was collected and washed with IPE-n-hexane to give P0032 (0.67g) as a white powder. 200MHz 1H NMR (CDC13, d) : 5.10(3H, s) , 6.97(2H, d, J=8.9 Hz), 7.34-7.43(5H, m) , 7.56(2H, d, J=8. 9 Hz) (E0102-0) (E0102) To a solution of P0032(99.9mg) and HOBT 64.2mg in N-methylpyrrolidone 1ml was added WSCD*HC1 91.1mg and the mixture was stirred at ambient temperature for 20minutes. In another flask, diisopropylethylamine 76.8mg was added to a suspension of E0102-0 (83.0mg) in N-methylpyrrolidone lml and stirred at ambient temperature until all E0102-0 was dissolved. The solution of E0102-0 was added to the reaction flask and the mixture was stirred at ambient temperature for lhour. The mixture was partitioned between AcOEt and H20, washed with sat. aqNaHC03, sat.aqNaCl, dried over MgS04, and concentrated in vacuo.The residue was dissolved in CH2C12 3ml, and stirred at ambient temperature for 24hours. The mixture was concentrated in vacuo. The residual crystals were suspended in hot AcOEt, cooled with stirring, collected and washed with AcOEt to give E0102 (90.9mg) as a white powder. Mass (ESI+) : 373 (M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 3.75(3H, s) , 5.08 (2H, s) , 5.81 (1H, s) , 6.90(2H, d, J=9.0 Hz) , 6.96(2H, d, J=9.0 Hz) , 7.10(2H, d, J=9.0 Hz), 7.12(2H, d, J=9.0 Hz), 7.32-7.47 (5H, m),. 10.00(1H, s) Example 103 MeCT^ (E0103) To a suspension of E0102 (20.9mg) and K2C03 23.3mg in DMSO 0.5ml was added dimethylsulfate 10.6mg and the mixture was stirred at ambient temperature for lhour. The mixture was partitioned between AcOEt and H20, and the organic layer was washed with sat.aqNaCl, dried over MgS04, concentrated in vacuo. The residue was purified by preparative thin layer chromatography developed with AcOEt / n-hexane = 25%. The obtained crystals were crystallized from IPE to give E0103 (12.0mg) as white crystals. Mass (ESI+) : 387 (M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 3.76(3H, s), 3.83(3H, s), 5.08(2H, s), 6.04(1H, s), 6.92(2H, d, J=9.0Hz), 6.97(2H, d, J=9.0 Hz), 7.11-7.17(4H, m) , 7.30-7.50(5H, m) 2 0 0MHz 1HNMR (CDC13, d) : 3.80 (3H, s) , 3.97 (3H, s) , 5.04 (2H, s), 5.88(1H, s), 6.82(2H, d, J=9.0Hz), 6.88(2H, d, J=8.9 Hz), 7.11-7.21(4H, m) , 7.34-7.43(5H, m) (E0104) To suspension of E0102 (818mg) and K2C03 911mg in DMF 6ml was added dimethylcarbonate 0.56ml. The mixture was stirred at 120°C for 2hours. Additional dimethylcarbonate lml was added and stirred at 120°C for 8hours. The mixture was partitioned between AcOEt and H20, and the aq layer was reextracted with AcOEt. The combined organic layers were washed with sat.aqNaCl, dried over MgS04, concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with AcOEt / n-hexane = 30%. The residue was crystallized from AcOEt 2.5ml and n-hexane 5ml to give E0104 (583mg) as white crystals. 20 0MHz 1HNMR (DMSO-d6, d) : 3.7 6 (3H, s) , 3.83(3H, s) , 5.08 (2H, s), 6.04(1H, s), 6.92(2H, d, J=9.0 Hz), 6.97(2H, d, J=9.0 Hz), 7.11-7.17(4H, m) , 7.30-7.50 (5H, m) 200MHz 1HNMR (CDC13, d) : 3.80 (3H, s) , 3.97 (3H, s) , 5.04 (2H, s), 5.88(1H, s), 6.82(2H, d, J=9.0Hz), 6.88(2H, d, J=8.9 Hz), 7.11-7.21(4H, m), 7.34-7.43(5H, m) (P0033) A mixture of 10% Pd-C 50% wet 50mg and E0104 (2 61mg) in AcOEt 2ml and MeOH 2ml was hydrogenated under H2 latm at ambient temperature for lday. The additional 10% Pd-C 50% wet 50mg was added and the mixture was hydrogenated under H2 3.5atm at ambient temperature for 3hours. The catalyst was filtered off and the filtrate and combined washings were concentrated in vacuo. The residue was dissolved in AcOEt, dried over MgS04, and concentrated in vacuo. The residue was crystallized from AcOEt-n-hexane to give P0033 (146mg) as a white powder. Mass (ESI+) : 297 (M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 3.75(3H, s) , 3.83 (3H, s) , 5.98 (1H," s), 6.70(2H, d, J=8.6Hz), 6.91(2H, d, J=8.9Hz), 7.01(2H, d, J=8.6 Hz), 7.12(2H, d, J=8.9 Hz), 9.69(1H/ s) (P0034) To a solution of ammmonium formate 4 55mg in H20 1ml was added EtOH 6ml, E0104 (558mg) , THF 1ml, and 10% Pd-C 50% wet 60mg successively. The mixture was refluxed for lhour. The catalyst was removed by filtration. The filtrate and combined washings were concentrated in vacuo. The residue was partitioned between AcOEt and H20, and the organic layer was washed with sat.aqNaCl, dried over MgS04, concentrated in vacuo. The residual crystals were recrystallized from AcOEt 3ml and n-hexane 3ml to give P0034 (335mg) as white crystals. Mass (ESI+) : 297 (M+H)+ / —^ A mixture of P0003 (2.9g) and 4-methoxyphenylhydrazine (1. 68g) in acetic acid (30ml) was stirred at room temperature for 15 hours. After addition of water, the mixture was extracted twice with toluene. The combined organic layer was washed with water (twice), sat.NaHC03, water and brine, dried over MgS04, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel ( Hex/EtOAc = 8:1-4:1) to give 2.2g (57%) of E0105 as an oil. IR (film): 1737.6, 1511.9, 1240.0, 1159.0, 1130.1 cm-1. \ (E0106) E0106 was prepared from P0004 in a similar manner to that of E0105. Mass (ESI+) : 420 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.7 9-1.94 (2H, m) , 1.98 (3H, s) , 2.60-2.68(2H, m), 3.88(3H, s), 3.98(2H, t, J=6.5Hz), 6.92(1H, d, J=8.9 Hz), 7.18(1H, s), 7.24(4H, s), 7.75(1H, dd, J=2.7,8.9 Hz), 8.48(1H, d, J=2.7 Hz) (E0107) E0107 (175.7mg) was prepared from P0007 (590mg) and 4-methoxyphenylhydrazine hydrochloride (332mg) in a similar manner to that of E0105. Mass (ESI+) : 455 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.96(3H, s) , 2.88 (2.H, t, J=6.8 Hz), 3.79(3H, s), 4.20(2H, t, J=6.8Hz), 6.99(2H, d, J=8.9 Hz), 7.15(1H, s), 7.17-7.30(6H, m) (E0108) E0108 was prepared from P0007 in a similar manner to that of E0105. Mass (API-ES positive) : 456 (M+H)+ , 478 (M+Na)+ 200MHz 1H NMR (DMSO-d6, d) : 1.96(3H, s) , 2.89(2H, t, J=6.8 Hz), 3.88(3H, s), 4.21(2H, t, J=6.8 Hz), 6.92(1H, d, J=8.8 Hz), 7.15-7.35(4H, m) , 7.21(1H, s) , 7.76(1H, dd, J=2.7,8.8 Hz), 8.17(1H, d, J=2.7 Hz) (E0109) E0109 was prepared in a similar manner to that of E0105. Mass (ESI+) 409(M+H)+, 431(M+Na)+ NMR: SE20.059 200MHz 1H NMR (DMS0-d6, d) : 1.31 (3H, t, J=7.1 Hz) , 1.96(3H, s) , 2.87 (2H, t, J=6.8Hz) , 3.79(3H, s) , 4.20 (2H, t, J=6.8 Hz) , 4.32(2H, q, J=7.1 Hz) , 6.99(2H, d, J=9.0 Hz) , 7.08(1H, s), 7.16-7.28(6H, m) (E0110) E0110 was prepared in a similar manner to that of E0105. Mass (ESI+) : 410 (M+H)+ 20 0MHz 1H NMR (DMSO-d6, d) : 1.32(3H, t, J=7 .1 Hz) , 1.96(3H, s), 2.89(2H, t, J=6.8 Hz), 3.88(3H, s) , 4.21(2H, t, J=6.8 Hz), 4.33(2H, q, J=7.1Hz), 6.92(1H, d, J=8.8Hz), 7.12(1H, s) , 7.19-7.32(4H, m) , 7.73(1H, dd, J=2.7,8.8 Hz) , 8.14(1H, d, J=2.7 Hz) (E0111) E0111 was prepared in a similar manner to that of E0105. Mass (API-ES positive) : 406(M+H)+ , 428(M+Na)+ 200MHz 1H NMR (DMSO-d6, d) : 1.96(3H, s), 2.89(2H, t, J=6.7 Hz), 3.88(3H, s), 4.21(2H, t, J=6.7Hz), 6.92(1H, d, J=8.8 Hz), 7.20(1H, s), 7.24(2H, d, J=8.7Hz), 7.30(2H, d, J=8.7 Hz), 7.76(1H, dd, J=2.7, 8.8 Hz), 8.18(1H, d, J=2.7 Hz) (E0112) E0112 was obtained according to a similar manner to that of E0105. (E0113) E0113 was obtained according to a similar manner to that of E0105. (E0114) E0114 was obtained according to a similar manner to that i of E0105. r (E0115) E0115 was obtained according to a similar manner to that of E0105. (E0116) E0116 was obtained according to a similar manner to that of E0105. (E0117) E0117 was obtained according to a similar manner to that of E0105. Example 118 (E0118) A mixture of E0105 (2.0g) and IN NaOH (15ml) in THF (40ml) was stirred at room temperature for 5 hours. After the reaction was completed, the mixture was neutralized with IN HC1 (15ml), extracted twice with ethylacetate, washed with IN HC1, sat.NaHC03, and brine, dried over NA2S04, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel (H/EA = 2:1-1:1) to give 1.14g (64%) of E0118 as a crystal, mp: 103-104°C IR (film): 3396.0, 1513.9, 1467.6, 1238.1, 1160.9, 1132.0 cm-1. (E0119) E0119 was prepared from E0217 in a similar manner to that of E0118. IR (neat) : 3359, 3332, 3325, 1658, 1651, 1624, 1614, 1545, 1533, 1500cm-l Mass (ESI+) : 421 (M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 2.71-2.79(2H, m) , 3.28-3.39(2H, m) , 3.76(2H, brs), 3.88(3H, s), 5.47(1H, br), 6.92(1H, d, J=8.9Hz), 7.18(1H, s), 7.24(4H, s), 7.74(1H, dd, J=2.7, 8.9 Hz), 7.80(1H, t, J=5.9 Hz), 8.19(1H, d, J=2.7 Hz) \ (E0120) E0120 was prepared from E0002 in a similar manner to that of E0118. IR (neat) : 3433, 3423, 3398, 3367, 2945, 1612, 1500cm-l Mass (ESI+) : 378 (M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 1.62-1.77(2H, m) , 2.57-3.65(2H, m) , 3.34-3.44(2H, m) , 3.88(3H, s), 4.48(1H, t, J=5.1 Hz), 6.92(1H, d, J=8.9Hz), 7.17(1H, s), 7.23(4H, s), 7.76(1H, dd, J=8.9,2.8 Hz), 8.18(1H, d, J=2.8 Hz) u (E0121) E0121 was prepared from E0268 in a similar manner to that r of E0118. white powder mp. 91-92°C IR (KBr) : 3491, 3471, 3437, 2941, 2239, 1610, 1508cm-l Mass (ESI+) : 336 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 3. 65-3.73 (2H, m) , 3.79 (3H, s) , 3.95-4.05(2H, m) , 4.87(1H, t, J=5.4 Hz) , 6.93(2H, d, J=8.8 Hz) , 7.00(2H, d, J=9.0 Hz) , 7.16(2H, d, J=8.8 Hz) , 7.28(2H, d, J=9.0 Hz), 7.32(1H, s) ( E0122) E0122 was prepared from E0353 in a similar manner to that of E0118. white powder mp. 158-159°C IR (KBr) : 3399, 2955, 1707, 1693, 1647, 1614, 1566, 1547, 1529, 1512cm-l Mass (ESI+) : 393 (M+H)+ 200MHz 1H NMR (DMS0-d6, d) : 2.44 (3H, s) , 3.66-3.74 (2H, m) , 3.80(3H, s) , 3.96-4.02(2H, m), 4.88(1H, t, J=5.4Hz), 6.94(2H, d, J=8.7 Hz) , 7.02(2H, d, J=8.9 Hz) , 7.22(2H, d, J=8.7 Hz), 7.26(1H, s), 7.3K2H, d, J=8. 9 Hz) (E0123) E0123 was prepared from E0358 in a similar manner to that of E0118. white powder mp. 105-107°C IR (KBr) : 3529, 3437, 2956, 1610, 1570, 1547, 1529cm-l Mass (ESI+) : 337 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 3.65-3.73 (2H, m) , 3.88 (3H, s) , 3.96-4.02(2H, m) , 4.87(1H, t, J=5.3 Hz) , 6.93(1H, d, J=8 . 8 Hz) , 6.96(2H, d, J=8.7 Hz) , 7.21(2H, d, J=8.7 Hz) , 7.35(1H, s), 7.73(1H, dd, J=2.7,8.8 Hz), 8.20(1H, d, J=2.7 Hz) (E0124) E0124 was prepared from E0107 in a similar manner to that of E0118. white powder mp. 97-98°C IR (KBr) : 3427, 2960, 1608, 1516cm-l Mass (ESI+) : 413 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 2.71(2H, t, J=6.9 Hz), 3.54-3.65(2H,m) , 3.7 9(3H, s) , 4.64 (1H, t, J=5.1Hz) , 7.00 (2H, d, J=9.0 Hz), 7.12(1H, s), 7.15-7.33(4H, m), 7.29(2H, d, J=9.0 Hz) Example 125 (E0125) E0125 was prepared in a similar manner to that of E0118. IR (neat) : 3435, 3425, 3406, 3398, 3367, 1691, 1658, 1647, 1614, 1547, 1512cm-l Mass (ESI+) : 320 (M+H)+ , 361(M+CH3CN+H)+ 200MHz 1H NMR (DMSO-d6, d) : 2.71(2H, t, J=6.8 Hz), 3.54-3.64(2H, m) , 3.79(3H, s), 4.64(1H, t, J=5.2Hz), 7.00(2H, d, J=8.9 Hz) , 7.15(2H, d, J=8.3 Hz) , 7.23(2H, d, J=8.3 Hz), 7.29(2H, d, J=8.9 Hz), 7.34(1H, s) (E0126) E0126 was prepared from E0111 in a similar manner to that of E0118. white powder mp. 89-92°C IR (KBr) : 3481, 2947, 1608, 1496cm-l Mass (ESI+) : 364 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 2.72(2H, t, J=6.8 Hz), 3.55-3.65 (2H,m) , 3. 88 (3H, s) , 4 . 65 (1H, t, J=5.2Hz) , 6.92(1H, d, J=8.8 Hz), 7.16(1H, s), 7.19-7.28 (4H, m), 7.77(1H, dd, J=2.6,8.8 Hz), 8.19(1H, d, J=2.6 Hz) (E0127) E0127 was prepared from E0108 in a similar manner to that of E0118. IR (neat) : 3400, 2951, 1610, 1502cm-l Mass (API-ES positive) : 414 (M+H)+ , 436 (M+Na)+ 200MHz 1H NMR (DMSO-d6, d) : 2.72(2H, t, J=6.9 Hz), 3.51-3.65(2H, m) , 3.88(3H, s), 4.65(1H, t, J=5.1Hz) , 6.93(1H, d, J=8.8 Hz), 7.15-7.35(4H, m) , 7.18(1H, s) , 7.77(1H, dd, J=2.7,8.8 Hz), 8.18(1H, d, J=2.7 Hz) (E0128) E0128 104.4mg was prepared in a similar manner to that of E0118. IR (neat) : 3433, 3423, 3398, 2947, 2873, 2243, 1608cm-l Mass (ESI+) : 321 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 2.72(2H, t, J=6.8 Hz), 3.55-3.65 (2H, m) , 3.88(3H, s) , 4.65(1H, t, J=5.1Hz) , 6.93(1H, d, J=8.8 Hz), 7.19(2H, d, J=8.4 Hz), 7.26(2H, d, J=8.4 Hz), 7.38(1H, s), 7.76(1H, dd, J=2.7,8.8 Hz) , 8.21(1H, d, J=2 . 7 Hz) (E0129) E0129 was obtained according to a similar manner to that of E0118. o \ (E0130) E0130 was obtained according to a similar manner to that of E0118. (E0131) E0131 was obtained according to a similar manner to that of E0118. (E0132) E0132 was obtained according to a similar manner to that of E0118. IR (film): 3392.2, 1494.6, 1236.2, 1160.9, 1133.9, 1095.4, 975.8, 833.1 cm-1. (E0133) E0133 was obtained according to a similar manner to that of E0118. IR (film): 3374.8, 1511.9, 1471.4, 1274.7, 1232.3, 1160.9, 1133.9, 977.7, 842.7, 811.9 cm-1. mp: 82-83 °C E0134 was obtained according to a similar manner to that of E0118. IR (film): 3386.4, 1511.9, 1471.4, 1236.2, 1159.0, 1132.0, 1047.2, 975.8, 817.7 cm-1. (E0135) E0135 was obtained according to a similar manner to that of E0118. IR (film): 3399.9, 1610.3, 1513.9, 1459.9, 1251.6, 1172.5, 1083.8, 1033.7, 836.9, 802.2 cm-1. (FS7081) (E0136) P0018 (277mg) and 4-methoxyphenylhydrazine hydrochloride (209mg) in EtOH:AcOH=20:1 6ml was refluxed for 2hours. The mixture was partitioned between AcOEt and H20. The organic layer was washed successively with 1M HC1, saturated aqueous sodium bicarbonate solution, and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica ael column chromatography eluted with AcOEt / n-hexane = 30%, 40%, 50%. Th'epure fraction was collected and concentrated in vacuo. The residue was crystallized from AcOEt / n-hexane to give E0136 (95.6mg) as a white powder. mp. 111-112°C IR (KBr) : 3325, 2931, 1707, 1693, 1685, 1658, 1647, 1564, 1549, 1514cm-l Mass (ESI+) : 335 (M+H) + 200MHz 1HNMR (DMSO-d6, d) : 0.69-0.77(2H, m) , 0.86-0.96(2H, m) , 1.93(1H, m) , 2.69(2H, t, J=6.9 Hz), 3.53-3.64(2H, m), 3.76(3H, s), 4.64(1H, t, J=5.2 Hz), 6.28(1H, s) , 6.92(2H, d, J=9.0 Hz), 7.05-7.19(6H, m) \ (E0137) E0137 was prepared from P0018 498.5mg in a similar manner to that of E0136. (P0034) P0034 was prepared in a similar manner to that of E0137. white powder Mass (ESI+) : 306 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 0.67-0.76(2H, m) , 0.84-0.94(2H, m) , 1.91(1H, m) , 3.76(3H, s), 6.18(1H, s), 6.68(2H, d, J=8.7 Hz), 6.91(2H, d, J=9.0 Hz) , 6.98(2H, d, J=8.7 Hz) , 7.12(2H, d, J=9.0 Hz) , 9.63(1H, s) (E0138) To a solution of E0118 (l.Og) and Et3N (0.6ml) in CH2C12 (20ml) was addeddropwisemethanesulfonylchloride (0.26ml) under ice-cooling. After stirring for 1 hour, the reaction mixture was quenched with water and extracted with CHC13. The organic layer was washed with water, dried over Na2S04, filtered and evaporated to give 1.2g (99%) of crude E0138 as an off-white solid. IR (film): 1513.9, 1469.5, 1351.9, 1240.0, 1166.7, 1130.1, 971.9, 835.0, 804.2cm-l. (E0139) E0139 was prepared in a similar manner to that of E00138. Mass (ESI+) : 459 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) 1.09-1.23(3H, m) , 2 . 98, 3.29 (3H, s), 3.01(2H, t, J=6.6Hz), 3.09(3H, s) , 3.43-3.77(2H, m) , 3.87(3H, s), 4.42(2H, t, J=6.6 Hz), 6.88-6.92(2H, m) , 7.25(2H, d, J=8.3 Hz), 7.33(2H, d, J=8.3 Hz), 7.65-7.73(lH, m) , 8.15(1H, d, J=2.6 Hz) (E0140) E0140 was prepared in a similar manner to that of E0138. Mass (APCI+) : 458 (M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 1. 05-1. 25 (3H, m) , 2 . 96-3 . 03 (2H, m) , 2.98,3.29(3H, s) , 3.08(3H, s) , 3 . 40-3.85(2H, m) , 3.78(3H, s), 4.42(2H, t, J=6.6Hz), 6.86,6.88(1H, s), 6.98(2H, d, J=8.9 Hz), 7.18-7.32(6H, m) (E0141) E0141 was prepared in a similar manner to that of E0138 . Mass (ESI+) : 456 (M+H)+ 20 0MHz 1HNMR (DMS0-d6, d) : 1. 89-2 . 04 (2H, m) , 2 . 52-2 . 73 (2H, m) , 3.16(3H, s) , 3.88 (3H, s) , 4.19(2H, t, J=6.3Hz) , 6.92(1H, d, J=8.9Hz), 7.18(1H, s), 7 . 21-7.31 (4H, m), 7.76(1H, dd, J=2.6,8.9 Hz), 8.19(1H, d, J=2.6 Hz) (E0142) E0142 was obtained according to a similar manner to that of E0138. (E0143) E0143 was obtained according to a similar manner to that of E0138. . —6 (E0144) This compound was obtained according to a similar manner to that of E0138. (E0145) This compound was obtained according to a similar manner to that of E0138. (E0146) This compound was obtained according to a similar manner to that of E0138. (E0147) This compound was obtained according to a similar manner to that of E0138. Example 14 8 (E0148) A mixture of E0138 (900mg) and potassium phthalimide (454mg) in DMF (18ml) was stirred at 6O0C for 3.0 hours. After addition of water, the reaction mixture was extracted with EtOAc and washed twice with water and with brine. The organic layer was dried over Na2S04 , filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel (50ml) to give 930mg (93%) of E0148 as a powder. IR (film): 1772.3, 1712.5, 1240.0, 1160.9, 1130.1cm-l. (E0149) E0149 was prepared from E0139 in a similar manner to that of E0148. amorphous powder Mass (ESI + ) : 510 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.08-1.22(3H, m), 2.89-2.98(2H, m), 2.98,3.27(3H, s), 3.48,3.70(2H, q, J-7.1,6.9 Hz), 3.82(2H, t, J=7.3 Hz), 3.88 (3H, s) , 6. 83-6. 88 (2H, m) , 7.23 (,2H, d, J=8.7Hz) , 7.18 (2H, d, J=8.7 Hz) , 7.53-7.63(1H, m) , 7.7 9-7.89(4H. m) . 8.15(1H. d, J=2.6 Hz) (E0150) E0150 was prepared from E0140 in a similar manner to that of E0148. amorphous powder Mass (ESI+) : 509 (M+H)+ 200MHz 1H NMR (DMS0-d6, d) : 1.12,1.18(3H, t, J=7.0,7.1 Hz), 2.92(2H, t, J=7.0Hz), 2 . 97 , 3 . 28 (3H, s), 3 . 47, 3 . 71 (2H, q, J=7.1,7.0 Hz), 3.78(3H, s), 3.81(2H, t, J=7.0 Hz), 6.82,6.84(1H, s), 6.94(2H, d, J=9.0Hz), 7.11-7.20(6H, m) , 7.79-7.89(4H, m) (E0151) E0151 was prepared from E0038 in a similar manner to that of E0148. Mass (ESI+) : 507 (M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 1.82-1.97(2H, m) , 2.59-2.67(2H, m), 3.60(2H, t, J=7.0 Hz), 3.88(3H, s), 6.91(1H, d, J=8.8 Hz), 7.14(1H, s), 7.20(2H, d, J=8.5Hz), 7.26(2H, d, J=8 .5 Hz) , 7.73(1H, dd, J=8.8 , 2.8 Hz) , 7.7 8-7.8 9(4H, m) , 8.17(1H, d, J=2.8 Hz) (E0152) This compound was obtained according to a similar manner to that of E0148. (E0153) This compound was obtained according to a similar manner to that of E0148. (E0154) This compound was obtained according to a similar manner to that of E0148. / F (E0155) This compound was obtained according to a similar manner to that of E0148. (E0156) This compound was obtained according to a similar manner to that of E0148. (E0157) This compound was obtained according to a similar manner to that of E0148. Example 158 (E0158) To a solution of E0148 (800mg) in CH3CN (10ml) was added hydrazine hydroxide (87ul) at room temperature. After stirring for 1 hour, the reaction mixture was filtered and evaporated. After addition of dichloromethane, themixture was stirred for an hour, filtered and evaporated. The residue was treated with 4NHCl/EtOAc to give 518mg (80%) of E0158. IR (Film); 3403.74, 1610.27, 1511.92, 1467.56, 1238.08, 1160.94, 1130.08, 1027.87, 975.80, 8 36.96, 806.10cm-l. (E0159) This compound was obtained according to a similar manner to that of E0158. (E0160) This compound was obtained according to a similar manner to that of E0158. (E0161) This compound was obtained according to a similar manner to that of E00158. IR (film): 3428.8, 1511.9, 1467.6, 1238.1, 1160.9, 1132.0cm-l. / F (E0162) This compound was obtained according to a similar manner to that of E0158. IR (film): 3371.0, 1511.9, 1471.4, 1272.8, 1230.4, 1160.9, 1133.9, 975.8, 842.7, 810.0cm-l. Example 163 (E0163) This compound was obtained according to a similar manner to that of E0158. mp: 163.1-165.1°C IR (film): 2973.7, 1511.9, 1471.4, 1236.2, 1159.0, 1133.9cm-l. (E0164) This compound was obtained according to a similar manner to that of E0158. IR(film): 3369.0, 1604.5, 1513.9, 1459.9, 1251.6, 1172.5, 1083.8, 1029.8,837.0, 800.3 cm-1. (E0165) To a solution of E0395 (1.08 g) in acetonitril (15 ml) was added hydrazine monohydrate (0.53 ml). After stirring at 60°C overnight, the mixture was filtered. And the filtrate was evaporated to give E0165 as an orange oil (814 mg, 102%) . NMR(CDC13), 2.76(2H, t, J=6.5 Hz), 2.98(2H, t, J=6.5 Hz), 3.94 (3H, s) , 6.73(1H, s) , 6.76(1H, d, J=8.9 Hz), 7.22-7.12(4H, m), 7.57(1H, dd, J=8.9, 2.7 Hz), 8.09(1H, d, J=2.7 Hz). MS(ESI+);363.3(MH+). (E0166) E0166 was prepared from E0046 in a similar manner to that of E0165. Mass (ESI+) : 380 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.91-1.23(3H, m) , 2.59-2.79(4H, m), 2.98,3.28(3H, s), 3.48,3.71(2H, q, J=7.2,7.0 Hz) , 3.87(3H, s) , 6.86-6.93(2H, m) , 7.16-7.26(4H, m), 7.64-7.73(1H, m), 8.15(1H, d, J=2 . 5 Hz) * (E0167) E0167 was prepared from E0150 in a similar manner to that of E0165. Mass (ESI+) : 379 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.08-1.22(3H, m), 2.57-2.78 (4H, m), 2.97,3.29 (3H, s), 3.48,3.72(2H, q, J=7.2, 7.0 Hz) , 3.78(3H, s) , 6.83,6.85(1H, s), 6.98(2H, d, J=8.9 Hz), 7.06-7.26(6H, m) (E0168) E0168 was prepared from E0048 in a similar manner to that of E0165. Mass (ESI+) : 377 (M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 1. 54-1. 69 (2H, m) , 2 . 4 9-2 . 64 (4H, m) , 3.88 (3H, s) , 6.92(1H, d, J=8.7Hz) , 7 .17 (1H, s) , 7 .22 (4H, s), 7.75(1H, dd, J=8.7,2.6 Hz), 8.18 (1H, d, J=2.6 Hz) \ (E0169) To a solution of E0165 (180 mg) in tetrahydrofuran (2 ml) was added triethylamine (0.242 ml) and t-butoxycarbonyl anhydride (325 mg) at room temperature. After stirring at room temperature overnight, the mixture was quenched with water and extracted with ethyl acetate (x3). The organic layer was washed with hydrogen chloride aqueous solution (IN) , saturated sodium hydrogen carbonate aqueous solution, and brine, dried over magnesium sulfate, and evaporated to giveoil, which waspurifiedwith column chromatography (Si02 25 ml, 20% ethyl acetate/hexane) to give E0169 as an oil (224 mg , 97.5%) . NMR(CDC13); 1.35(9H, s), 2.69(2H, t, J=7.7 Hz), 3. 09-3.19 (2H, m) , 3.88 (3H, s) , 6.9K1H, d, J=8.8Hz) , 7.17 (1H, s) , 7.18-7.27(4H, m) , 7.75(1H, dd, J=8.8, 2.7 Hz), 8.19(1H, d, J=2.7 Hz). MS(ESI+); 485.2(M+Na). (E0170) This compound was obtained according to a similar manner to that of E0169. NMR(CDC13), 1.45(9H, s), 3.49-3.57(2H, m), 3.82(3H, s), 4.01(2H, t, J=5.1Hz), 6.67(1H, s), 6.82(2H, d, J=8.7Hz), 6.87(2H, d, J=9.0 Hz), 7.13(2H, d, J=8.7 Hz), 7.22(2H, d, J=9.0 Hz) . MS(ESI+), 500.2(M+Na). Example 171 (E0171) A mixture of E0158 (650mg) , Boc20 (428mg) and INNaOH (3-3ml) in THF (20ml) was stirred at room temperature for 15 hours. Water and EtOAc was added and the aqueous layer was separated and extracted with EtOAc. The combined organic layer was washed with sat NaHC03, water and brine, dried over NA2S04, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel (Hex/EtOAc) to give 700mg (93%) of E0171 as an oil. (E0172) This compound was obtained according to a similar manner to that of E0171. This compound was obtained according to a similar manner to that of E0171. (E0174) This compound was obtained according to a similar manner to that of E0171. IR (film): 1702.8, 1513-9, 1241.9, 1164.8, 1132.0cm-l. (E0175) To a solution of E0171 (200mg) and Mel (0.14ml) in THF (20ml) was added portionwise NaH (35mg) at room temperature . Then the reaction mixture was heated at 70oC for 1 hour. Almost no reaction. Mel (0.3ml) and NaH (40mg) was added, and DMF was added. The mixture was stirred at 70°C for 12 hours, and then cooled, quenched with water. The aqueous layer was extracted twice with EtOAc. The combined organic layer was washed with water and brine, dried over MgS04, filtered and evaporated. The residue was column chromatographed on silica gel to give 151mg (73%) of E0175 as an oil. ■(E0176) This compound was obtained according to a similar manner to that of E0175. (E0177) To a mixture of E0158 (150mg) and HCHO (46ul) in Et3N (53ul) and CH3CN (5ml) was added portionwise NaBH(0Ac)2 (240mg) at room temperature - After stirring for 15 hours, the mixture was quenched with water and extracted three times withEtOAc. The combined organic layer was washed with water and brine, dried over Na2S04, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel (CHC13/MeOH) and treated with 4NHCl/dioxane to give 108mg (70%) of E0177. Example 17 8 (E0178) Methylisocyanate 36.2mg was added to a solution of E0165 (199.3mg) and triethylamine 48.6mg in CH2C12 2ml under ice bath cooling. The reaction mixture was stirred at same temperature for lhour and concentrated in vacuo. The residue was partitioned between AcOEt and 1M HC1. The organic layer was washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was recrstallized fromAcOEt-n-hexane. Obtained powder was dissolved in CHC13 and further purified by preparative thin layer silica gel chromatography developed by MeOH / CHC13 = 10% . The seaparated silica gel was extracted with 10% MeOH/CHC13 and the solvent was evaporated in vacuo. The residual solid was collected and washed with diisopropyl ether to give E0178 (101.3mg) as a white powder, mp. 149°C IR (KBr) : 3348, 2947, 2885, 1626, 1583, 1529, 1500cm-l Mass (ES1 + ) : 420 (M+H) + 200MHz 1H NMR (DMSO-d6, d) : 2 . 49-2.53 (3H, overlapping), 2.64-2.72(2H, m) , 3.15-3.26(2H, m) , 3.88(3H, s) , 5.72(1H, q, J=4.5 Hz) , 5.89(1H, t, J=5.7 Hz) , 6.92 (1H, d, J=8.8 Hz) , 7.17(1H, s), 7.24(4H, s) , 7.76(1H, dd, J=2.7, 8.8 Hz), 8.19(1H, d, J=2.7 Hz) Example 17 9 (E0179) E0179 80.7mg was prepared from E0166 in a similar manner to that of E0178. amorphous powder IR (neat) : 3350, 2950, 2930, 1707, 1691, 1674, 1645, 1641, 1622, 1614, 1566, 1549, 1533, 1510cm-l Mass (ESI+) : 437 (M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 1. 09-1. 23 (3H, m) , 2 . 49-2 . 54 (3H, overlapping), 2.67(2H, t, J=7.2 Hz), 2.98,3.28(3H, s), 3.15-3.28(2H, m) , 3.48,3.71(2H, q, J=6.8, 6.9 Hz) , 3.88(3H, s), 5.73(1H, q, J=4.6 Hz), 5.90(1H, t, J=5.6 Hz), 6.86-6.93(2H, m) , 7.22(4H, s) , 7.64-7.73(1H, m) , 8.15(1H, d, J=2.6 Hz) (E0180) E0180 was prepared from E0294 in a similar manner to that of E0178. white powder mp. 155-157°C IR (KBr) : 3336, 2968, 1707, 1693, 1674, 1621, 1576, 1533cm-l Mass (ESI+) : (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 0.96(3H, t, J=7.1 Hz), 2.64-2.72(2H, m) , 2.91-3.05 (2H, m) , 3.15-3.26(2H, m) , 3.88 (3H, s) , 5.7 6-5.84(2H, m), 6.92(1H, d, J=8.8Hz), 7.17(1H, s), 7.24(4H, s), 7.76(1H, dd, J=8.8,2.7 Hz), 8.19(1H, d, J=2.7 Hz) (E0181) This compound was obtained according to a similar manner to that of E0178. IR (film) : 3343.9, 1658.5, 1608.3, 1513.9, 1457.9, 1249.6, 1029.8, 836.9 cm-1. CI (E0182) This compound was obtained according to a similar manner to that of E0178. IR (Film): 1659.0, 1608.8, 1554.8, 1485.4, 1470.0, 1240.4, 1165.1, 1134.3, 1097.6, 835.3cm-l. Example 183 (E0183) This compound was obtained according to a similar manner to that of E0178. IR (film): 3249.8, 1658.5, 1608.3, 1554.3, 1469.5, 1240.0, 1164.8, 1133.9, 1097.3, 975.8, 835.0 cm-1. (E0184) AcCl 23.3mg was added to E0158 (107. 4mg) and triethylamine 68.3mg in CH2C12 2ml with cooling in an ice bath. After stirring at same temperature for lhour, the reaction mixture was concentrated in vacuo. The residue was partitioned between AcOEt and 1M HC1. The-organic layer was washed with saturated aqueous sodiumbicarbonate solution and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residual solid were collected and washed with diisopropyl ether to give E0184 (84mg) as a white powder, mp. 79-80°C IR (KBr) : 3307, 3221, 3093, 2964, 1689, 1639, 1554, 1514cm-l Mass (ESI+) : 404 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.76(3H, s) , 2. 65-2. 7 3 (2H, m) , 3.18-3.31(2H, m), 3.79(3H, s), 6.99(2H, d, J=8.9Hz), 7.12 (1H, s) , 7.20(4H, s), '7.28(2H, d, J=8.9 Hz), 7.92(1H, t, J=5.4 Hz) (E0185) E0185 (143.4mg) was prepared from E0232 (155.3mg), methyl chloroformate 35.8mg, and triethylamine 105mg in a similar manner to that of E0184. amorphous powder IR (neat) : 3319, 2954, 1718, 1711, 1668, 1660, 1612, 1545, 1533, 1500cm-l Mass (ESI + ) : 178 (M+H) + 200MHz 1HNMR (DMSO-d6, d) : 2 . 67-2 . 75 (2H, m) , 3 . 22-3 . 33 (2H, m), 3.50-3.60(2H, overlapping), 3.53(3H, s), 3.88(3H, s), 6.92(1H, d, J=8.8Hz), 7.18(1H, s), 7.24(4H, s), 7.28(1H, t, J=6Hz), 7.75(1H, dd, J=2.7,8 . 8 Hz), 7.94(1H, t, J=5.6 Hz) , 8.19(1H, d, J=2.7 Hz) (E0186) E0186 (59.3mg) was prepared from E0158 (96.2mg), methyl chloroformate 25.1mg and triethylamine 61.2mg in a similar manner to that of E0184. mp. 78-80°C IR (KBr) : 3352, 1739, 1695, 1658, 1647, 1549, 1514cm-l Mass (ESI+) : 420 (M+H)+ 2 00MHz 1HNMR (DMSO-d6, d) : 2.66-2.7 4(2H, m) , 3.14-3.25(2H, m) , 3.49(3H, s) , 3.79(3H, s) , 6.99(2H, d, J=8.9Hz) , 7.12(1H, s), 7.12-7.32(1H, m), 7.20(4H, s), 7.28(2H, d, J=8.9 Hz) (E0187) E0187 (63.4mg) was prepared from E0165 (113.6mg), acetyl chloride 29.5mg, andtriethylamine 41.2mg in a similarmanner to that of E0184. white powder mp.97-98°C IR (KBr) : 3311, 2956, 1674, 1641, 1543, 1500cm-l Mass (ESI+) : 405 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.76(3H, s) , 2.66-2.74 (2H, m) , 3.19-3.30(2H, m) , 3.88(3H, s) , 6.92(1H, d, J=8.8Hz) , 7.18(1H, s), 7.24(4H, s), 7.75(1H, dd, J=8.8,2.6 Hz), 7.92(1H, t, J=5.3 Hz), 8.19(1H, d, J=2.6 Hz) Example 188 (E0188) E0188 was prepared from E0165 in a similar manner to that of E0184 . IR (neat) : 3338, 3020, 2951, 1716, 1610, 1527, 1500cm-l Mass (ESI+) : 421 (M+H)+ 200MHz 1HNMR (DMS0-d6, d) : 2 . 67-2 . 75 (2H, m) , 3 .14-3 . 25 (2H, m) , 3.49(3H, s), 3.88(3H, s), 6.92(1H, d, J=8.9 Hz), 7.15-7.35(5H, m) , 7.18(1H, s) , 7.75(1H, dd, J=2.7,8.9 Hz) , 8.19(1H, d, J=2.7 Hz) (E0189) E0189 was prepared from E0294 in a similar manner to that of E0184. IR (neat) : 3352, 2939, 1691, 1639, 1533, 1500cm-l Mass (ESI+) : 434 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 2.67-2.74(2H, m) , 2.74(6H, s) , 3.15-3.26(2H, m) , 3.88(3H, s) , 6.34(1H, t, J=5.4Hz) , 6.92(1H, d, J=8.9 Hz), 7.17CLH, s) , 7.23(4H, s) , 7.75(1H, dd, J=8.9,2.7 Hz), 8.19(1H, d, J=2.7 Hz) (E0190) This compound was obtained according to a similar manner to that of E0189. NMR(CDC13); 2.7 8(3H, d, J=5.0Hz), 3.56-3.64(2H, m) , 3.82(3H, s) , 4.03(2H, t, J=5.1 Hz) , 4.2-4.4(1H, m, NH) , 4.6-4.9(lH, m, NH), 6.67(1H, s), 6.80-6.91(4H, m), 7.13(2H, d, J=8.8 Hz), 7.22(2H, d, J=9.0 Hz). MS (ESI + ) .457.1(M+Na) . IR(NBr), 1627.6cm-l (E0191) This compound was obtained according to a similar manner to that of E0184. IR (film): 3299.6, 1658.5, 1550.5, 1515.8, 1467.6, 1240.0, 1164.8, 1132.0, 975.8, 829.2, 755.9 cm-1. Example 192 (E0192) E0158 (250mg) was suspended in AcOEt 5ml and was partitioned between AcOEt and saturated aqueous sodium bicarbonate solution. The organic layer was washed with aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was dissolved in dimethoxyethane 5ml, sulfamide 181mg was added and refluxed for 2days. The reacion mixture was concentrated in vacuo, and the residue was purified by silica gel column chromatography eluted with MeOH / CHC13 = 1%, 2%, then 3%. Obtained amorphous powder was crystallized from EtOH-diisopropyl ehter to give E0192 153mg as a white powder, mp. 127-128°C IR (KBr) : 3357, 1707, 1693, 1647, 1564, 1549, 1529, 1514cm-l Mass (ESI+) : 441 (M+H)+ 4 00MHz 1HNMR (DMSO-d6, d) : 2 . 76-2 . 80 (2H, m) , 3.06-3.11 (2H, m) , 3.79(3H, s), 6.53(2H, s), 6.53-6.61(1H, broad), 7.00 (2H, d, J=8.9 Hz) , 7.12(1H, s) , 7.21(2H, d, J=8.5 Hz), 7.24(2H, d, J=8.5 Hz), 7.29(2H, d, J=8.9 Hz) E0193 was prepared from E0294 in a similar manner to that of E0192. white powder mp.ll4-115°C IR (KBr) : 3489, 3469, 3458, 3435, 3425, 3398, 3363, 3280, 1647, 1500cm-l Mass (ESI+) : 442 (M+H)+ 20 0MHz 1HNMR (DMSO-d6, d) : 2.75-2.83(2H, m) , 3.00-3.20(2H, m) , 3.88(3H, s) , 6.45-6.67(3H, m) , 6.92(1H, d, J=8.7 Hz), 7.18(1H, s) , 7.21-7.31 (4H, m) , 7.76(1H, dd, J=2.6,8.7 Hz) , 8.19(1H, d, J=2.6 Hz) (E0194) E0194 was prepared from E0322 in a similar manner to that of E0192. white powder mp. 142-143°C IR (KBr) : 3415, 3323, 3111, 3093, 3010, 2962, 1614, 1516cm-1 Mass (ESI+) : 429 (M+H)+ 200MHz1HNMR (DMSO-d6, d) : 0.68-0.76(2H, m) , 0.8 5-0.95(2H, m) , 1.92(1H, m) , 3.15-3.31(2H, m) , 3.7 6(3H, s) , 4.00-4.07(2H, m) , 6.25(1H, 1), 6.60(2H, brs), 6.72(1H, brs), 6.86-6.96(4H, m) , 7.10(2H, d, J=8.7 Hz), 7.13(2H, d, J=8.9 Hz) Example 195 (E0195) This compound was obtained according to a similar manner to that of E0192. NMR(CDC13) , 3.50-3.59(2H, m), 3.82(3H, s) , 4.14 (2H, t, J=4.9 Hz), 6.68(1H, s), 6.80-6.90(4H, m) , 7.15(2H, d, J=8.8 Hz), 7.22(2H, d, J=9.0 Hz). IR(KBr); 1612, 1552cm-l. MS(ESI+), 479.1(M+Na). (E0196) To a solution of E0158 (lOOmg) and Et3N (53ul) in CHC13 (10ml) was added MsCl (29ul) at room temperature. After stirring for 1 hour, the reaction mixture was poured onto water and CHC13. The aqueous layer was separated and extracted with CHC13. The combined organic layer was washed with water and brine, dried over Na2S04, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel (50ml) and crystalized to give 75mg (68%) of E0196 as a powder. IR (film): 3284.2, 1513.9, 1319.1, 1240.0, 1151.3, 973.9cm-l. (E0197) E0197 was prepared from E0166 in a similar manner to that of E0196. mp.l37-138°C IR (KBr) : 3222, 1691, 1684, 1658, 1645, 1610, 1566, 1547, 1531cm-l Mass (ESI+) : 458 (M+H)+ 200MHz 1H NMR (DMS0-d6, d) 1.09-1.22(3H, m), 2.73-2.81(2H, m), 2.80(3H, s), 2.98,3.28(3H, s), 3.09-3.30(2H, m), 3.48,3.71(2H, q, J=7.0, 6.8Hz), 3.87(3H, s), 6.88-6.93(2H, m) , 7.10(1H, brs) , 7.22(2H, d, J=8.5Hz), 7.28(2H, d, J=8.5Hz), 7 . 64-7 . 73 (1H, m), 8.15(1H, d, J=2.5 Hz) (E0198) E0198 was prepared from E0167 in a similar manner to that of E0196. mp.l62-163°C IR (KBr) : 3224, 1610, 1547, 1512cm-l Mass (ESI+) : 457 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.08-1.22(3H, m) , 2.76(2H, t, Jr=7.2 Hz), 2.80(3H, s) , 2.98,3.29(3H, s), 3.12-3.23(2H, m), 3.48,3.73(2H, q, J=7.2,6.9 Hz) , 3.78(3H, s) , 6.84,6.87(1H, s) , 6.98(2H, d, J=9.0 Hz), 7.09(1H, t, J=5.7 Hz), 7.16-7.26(6H, m) (E0199) E0199 was prepared from E0234 i\\ a similar manner to that of E0196. white powder, mp. 155°C IR (KBr) : 3265, 2974, 2937, 1682, 1612, 1512cm-l Mass (ESI+) : 458 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.15(6H, d, J=6.8 Hz) , 2.94(3H, s), 3.27-3.36(2H, m), 3.68(1H, m), 3.79(3H, s), 4.03(2H, t, J=5.5 Hz) , 6.93(2H, d, J=8.8 Az) , 6.98(1H, s) , 7.00(2H, d, J=8.9Hz), 7.19(2H, d, J=8.8Hz), 7.28(2H, d, J=8.9Hz), 7.17-7.30(1H, overlapping) (E0200) E0200 was prepared from E0235 ijn a similar manner to that of E0196. white powder mp. 149-153°C IR (KBr) : 3321, 1693, 1658, l|647, 1610, 1547, 1510cm-l Mass (ESI+) : 413 (M+H)+ 200MHz 1H NMR (DMS0-d6, d) : 2.93|(3H, s) , 3.27-3. 35 (2H, m) , 3.79(3H, s), 4.03(2H, t, J=5.5 Hz), 6.95(2H, d, J=8.7 Hz), 7.01(2H, d, J=9.0 Hz), 7.18(2H, d, J=8.7 Hz), 7.28(2H, d, J=9.0 Hz), 7.3K1H, s), 7.15-7L31HH. overlaDoina) (E0201) E0201 was prepared from E0294 liti a similar manner to that of E0196. IR (neat) : 3298, 2952, 2885, 1|612, 1566, 1547, 1529cm-l Mass (ESI+) : 470 (M+H)+ 200MHz 1H NMR (DMS0-d6, d) : 2.56(6H, s) , 2 . 71-2 . 79 (2H, m) , 3.07-3.17 (2H,m), 3.88 (3H, s) , 6.92(1H, d, J=8.7Hz) , 7.18 (1H, s) , 7.19-7. 30 (5H, m) ,, 7.7 7 (1H, dti, J=8 . 7 , 2 . 6 Hz) , 8.18 (1H, d, J=2.6 Hz) Example 202 (E0202) E0202 was prepared from E0322 iji a similar manner to that of E0196. white powder mp. 166-168°C IR (KBr) : 3093, 2964, 2873, 2^54, 1614, 1516cm-1 t Mass (ESI+) : 428 (M+H)+ • i 200MHz 1HNMR (DMS0-d6, d) : 0 . 68-0 . 76 (2H, m) , 0 . 85-0 . 95 (2H, m), 1.92(1H, m), 2.93(3H, s), 3 . 27-3.36(2H, m), 3.76(3H, s), 3.98-4.04 (2H, m), 6.25(1H, js) , 6.90(2H, d, J=8.7 Hz), 6.92(2H, d, J=8.9 Hz), 7.11(2H, d, J=8.7 Hz), 7.13(2H, d, J=8.9 Hz), 7.27(1H, t, J=5.8 HE) (E0203) This compound was obtained according to a similar manner to that of E00196. MS(ESI+); 454.1(MH+). IR(KBr); 1612.2, 1515.8cm-l. NMR(CDC13), 3.03(3H, s), 3.51-B.59(2H, m), 3.82(3H, s), 4.10(2H, t, J=4.9Hz), 6.68(lH,|s), 6.82(1H, d, J=8.7Hz), 6.88 (1H, d, J=8.9 Hz) , 7.15 (1H,I d, J=8 . 7 Hz) , 7.22 (1H, d, This compound was obtained accqramg to a similar manner to that of E0196. NMR(DMS0-d6); 2.80(3H, s) , 2.7 3-2.8 4(2H, m) , 3.13-3.22(2H, m) , 3.88(3H, s), 6.92(1H, d, J=9.0 Hz), 7.08-7.13(1H, m), 7.19(1H, s) , 7.22-7.33(4H, m) , 7.76(1H, dd, J=9.0, 2.6 Hz) , 8.19(1H, d, J=2.6 Hz). MS(ESI+),463.1(M+Na). IR(KBr), 3136, 1614, 1554, 114ftcm-l. (E0205) This compound was obtained according to a similar manner to that of E0196. Example 206 (E0206) This compound was obtained according to a similar manner to that of E0196. mp: 134.2-134.5°C IR (film): 3284.2, 1610.3, 1513.9, 1457.9, 1321.0, 1251.6, 1151.3, 1083.8, 1031.7, 838.9, 802.2, 757.9 cm-1. (E0207) This compound was obtained according to a similar manner to that of E00196. IR (film): 3286.11, 1606.41, ]J513.85, 1457.92, 1319.07, 1251.58, 1153.22, 1081.87, 102^9.80, 836.955 cm-1. (E0208) This compound was obtained according to a similar manner i to that of E0196. IR(film): 3284.2, 1513.9, 1317 .jl, 1240.0, 1153. 2cm-l. (E0209) This compound was obtained according to a similar mantiei to that of E0196. IR (film): 3286.1, 1511.9, 132l[0, 1230.4, 1155.2, 975.8, ■ 842.7, 756.0cm-l. (E0210) This compound was obtained according to a similar manner to that of E0196. IR (film): 3284.2, 1511.9, 1469J5, Y621.U, 1ZJ6.2, 1153.2, 975.8, 821.5, 756.0cm-l. Example 211 (E0211) This compound was obtained accdrdinq to a similar manner to that of E0196. IR (film): 3289.9, 1612.2, 1513.9, 1322.9, 1251.6, 1155.1, 1085.7, 1029.8, 975.8, 836.9, 1796.4 cm-1. (E0212) This compound was obtained according to a similar manner to that of E0196. IR (film): 3266.8, 1612.2, 1469|.5, 1321.0, 1240.0, 1153.2, 1097.3, 975.8, 835.0 cm-1. (E0213) This compound was obtained according to a similar manner to that of E0196. IR (film): 3288.0, 1612.2, 1322.9, 1240.0,'1153.2, 975.8, 94 6.9 cm-1. (E0214) A mixture of E0158 (180mg), formic acid (38ul), and WSCD (155mg) in Et3N (0.3ml) and THF (5ml) was stirred at room temperature for 1 hour. After addition of water and EtOAc, the aqueous layer was separated and extracted twice with EtOAc. The combined organic layer was washed with 1NHC1, sat.NaHC03, water and brine, dried over Na2S04, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel (Hex/EtOAc=2 :1) to give 136mg (70%) of E0214 as a powder. IR (film): 1670.1, 1513.9, 1238.1, 1160.9, 1130.1cm-l. (E0215) A mixture of E0158 (250mg), aocuxy (132mg), WSCD (127mg) andHOBt (HOmg) inEt3N (114ul) andCH2C12 (30ml) was stirred at room temperature. After stir ting for 15 hour, the reaction mixture was poured onto water and CHC13. The aqueous layer was separated and extracted with CHC13. The combined organic layer was washed with water and brine, dried over Na2S04, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel (50ml) and crystalized to give 325mg (99%) of E0215 as an oil. (E0216) E0216 was prepared in a similar manner LU umi. WJ. ^^^15. oil IR (neat) : 3431, 3421, 3404, 3400, 2939, lb!4, 1570, 1547cm-l Mass (ESI+) : 381(M+H) + 200MHz 1H NMR (DMS0-d6, d) : 1.0 9-1.23(3H, m) , 2.72(2H, t, J+6.9 Hz) , Z.ya,3.29(3H, s) , 3.42-3.77(4H, m) , 3.88(3H, s) , 6.86-6.93(2H, m) , 7.19(2H, d, J=8.5 Hz), 7.24(2H, d, J=8j5 Hz), 7.65-7.74(1H, m), 8.15(1H, d, J=2.6 Hz) (E0217) E0217 was prepared from E0294 and acetoxyacetic acid in a similar manner to that of E0215. oil Mass (ESI+) : 463(M+H) + 200MHz 1H NMR (DMSO-d6, d) : 2.07 (3H, s) , 2.69-2.77 (2H, m) , 3.24-3.33 (2H, m) , 3.88(3H,.s) , 4.40 (2H, s) , 6.92 (1H, d, J=8.7 Hz), 7.18(1H, s), 7.24(4H, s), 7.75(1H, dd, J=2.7,8.7 Hz) , 8.10(1H, t, J=5.6 Hz), 8.19(1H, d, J=2.7 Hz) (E0218) E0218 was prepared from E0294 and N-tert-butoxycarbonyl glycine in a similar manner to that of E0215 using N-methylmorpholine 55.8mg instead of triehtylamine. amorphous powder IR (neat) : 3315, 1707, 1693, 1684, 1676, 1658, 1649, 1624, 1614, 1564, 1547, 1533, 1510, 1500cm-l Mass (ESI+) : 520 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.37(9H, s) , 2.67-2.75(2H, m) , 3.22-3.33(2H, m) , 3.47(2H, d, J=6.0 Hz), 3.88(3H, s), 6.8 0-7.00 (1H, overlapping), 6.92(1H, d, J=8.8 Hz) , 7.17(1H, s), 7.24(4H, s), 7.75(1H, dd, J=8.8,2.7 Hz), 7.86(1H, t, J=5.6 Hz), 8.19(1H, d, J=2.7 Hz) Example 219 (E0219) E0219 was prepared in a similar manner to that of E0215. oil IR (KBr) : 3329, 3313, 3303, 1620, 1564, 1547, 1512 cm-1 Mass (ESI+) : 380 (M+H)+ 200MHz 1H NMR (DMS0-d6, d) : 1.08-1.22 (3H, m) , 2.71(2H, t, J=6.9 Hz) , 2.97,3.29 (3H, s) , 3.42-3.7 8(4H, m) , 3.78(3H, s) , 4.65(1H, t, J=5.1 Hz), 6.82,6.85(1H, s), 6.98(2H, d, J=8.9 Hz), 7.12-7.27(6H, m) (E0220) E0220 was prepared in a similar manner to that of E0215. Example 221 (E0221) E0221 was prepared in a similar manner to that of E0215. white powder mp. 95-101°C IR (KBr) :. 3421, 1693, 1647, 1603, 1566, 1549, 1516cm-l Mass (ESI+) : 396 (M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 1. 08-1. 22 ( 3H, m) , 2 . 97, 3 . 29 (3H, s) , 3.42-3.7 4(4H, m) , 3.78(3H, s) , 3. 95-4.00(2H, m) , 4.8 6(1H, t, J=5.4 Hz), 6.78,6.81 (1H, s) , 6.91(2H, d, J=8.8 Hz), 6.98(2H, d, J=8.8 Hz), 7.16(2H, d, J=8.8 Hz), 7.23(2H, d, J=8.8 Hz) (E0222) E0222 was prepared in a similar manner to that of E0215. white powder Mass (ESI+) : 398 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 3.38 (3H, s) , 3.65-3.74 (2H, m) , 3.77(3H, s), 3.78(3H, s), 3.95-4.01(2H, m) , 4.87(1H, t, J=5.4 Hz), 6.89(1H, s), 6.92(2H, d, J=8.8Hz), 6.99(2H, s, J=8.9 Hz), 7.17(2H, d, J=8.8 Hz), 7.24(2H, d, J=8.9 Hz) E0223 was prepared in a similar manner to that of E0215. white powder mp. 110-111°C IR (KBr) : 3425, 2979, 2945, 1606, 1570, 1549cm-l Mass (ESI+) : 397 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.09-1.23(3H, m), 2.98,3.28(3H, s) , 3.42-3.73(4H, m), 3.87(3H, s), 3.96-4.02(2H, m), 4.87(1H, t, J=5.3 Hz), 6.82-6.97(4H, m) , 7.21 (2H, d, J=8.7Hz), 7.63-7.72(1H, m) , 8.14(1H, d, J=2.6 Hz) (E0224) E0224 was prepared in a similar manner to that of E0215. white powder Mass (ESI+) : 399 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 3.37 (3H, s) , 3.66-3.74 (2H, m) , 3.77 (3H, s) , 3.88(3H, s), 3.96-4.02(2H, m) , 4.87(1H,t, J=5.5 Hz), 6.88-6.97(4H, m) , 7.21(2H, d, J=8.7 Hz), 7.69(1H, dd, J=2.7,8.8 Hz), 8.16(1H, d, J=2.7 Hz) (E0225) E0225 was prepared in a similar manner to that of E0215. white powder Mass (ESI+) : 495(M+H)+ 400MHz 1H NMR (DMS0-d6, d) : 1. 12,1.18(3H, t, J=7.0Hz), 1.37(9H, s) , 2 . 97 , 3.29(3H, s) , 3.24-3.28 (2H, m), 3.48 , 3.45(2H, q, J=7.0 Hz), 3.78(3H, s) , 3.95(2H, t, J=5.7 Hz), 6 . 78, 6.81(1H, s) , 6.91(2H, d, J=8.8 Hz), 6.98(2H, d, J=8.8 Hz), 7.00(1H, overlapping) , 7.16(2H, d, J=8.8 Hz), 7.23(2H, d, J=8.9 Hz) (E0226) E0226 was prepared in a similar manner to that of E0215. white powder Mass (ESI+) : 497 (M+H)+ 4 00MHz 1H NMR (DMSO-d6, d) : 1.37 (9H, s) , 3.25-3 . 29 (2H, m) , 3.37(3H, brs), 3.76(3H, s) , 3.78(3H, s) , 3.95(2H, t, J=5.7 Hz), 6.88(1H, s), 6.91(2H, d, J=8.8 Hz), 6.99(2H, d, J=8.9 Hz), 6.97-7.00(lH, br) , 7.17(2H, d, J=8.8Hz), 7.24(2H, d, J=8.9 Hz) Example 227 (E0227) E0227 was prepared in a similar manner to that of E0215. white powder Mass (ESI+) : 498 (M+H)+ 200MHz 1H NMR (DMS0-d6, d) : 1.37(9H, s), 3.22-3.33(2H, m), 3.37 (E0228) This compound was obtained according to a similar manner to that of E0215 as an oil (371.9 mg, 96%). NMR(CDC13); 1.43(9H, s), 3.65-3.73(2H, m) , 3.79-3.82(2H, m), 3.82(3H, s) , 4.03(2H, t, J=5.2 Hz), 6.67(1H, s), 6.79-6.89(4H, m) , 7.14(2H, d, J=8.7 Hz), 7.22(2H, d, J=9.0 Hz) . MS(ESI+); 557.2(M+Na). Example 229 (E0229) This compound was obtained according to a similar manner to that of E0289 as a white powder. NMR(DMS0-d6),3.49-3.63(4H, m), 3.79(3H, s), 4.03(2H, t, J=4.8 Hz) , 6.92-7.08(5H, m) , 7.21(2H, d, J=8.7 Hz) , 7.28(2H, d, J=8.9 Hz). MS(ESI-), 433.2(M-H). IR(KBr); 1683cm-1 (E0230) This compound was obtained according to a similar manner to that of E0215. IR (film): 3320.82, 1706.69, 1668.12, 1515.77, 1249.65, 1168.65, 1031.73 cm-1. (E0231) A mixture of E0215 (300mg) and 4NHC1 in dioxane (5.8ml) was stirred at room temperature for 1.0 hour. After then, the reaction mixture was evaporated under reduced pressure to give 260mg (99%) of E0231 as an amorphous. IR(film): 3226.3, 1679.7, 1513.9, 1251.6, 1083.8, 1029.8, 837.0cm-l. o (E0232) E0232 was prepared in a similar manner to that of E0231. white powder IR (KBr) : 3458, 3435, 3404, 3244, 3078, 3026, 1671, 1614, 1579, 1566, 1554, 1500cm-l Mass (ESI+) : 420 (M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 2 . 71-2. 79 (2H, m) , 3.30-3.41 (2H, m), 3.44-3.54 (2H, m), 3.88(3H, s), 6.93(1H, d, J=8.7 Hz), 7.22(1H, s) , 7.22-7.33(4H, m) , 7.77(1H, dd, J=2.7,8.7 Hz), 8.10(2H, br) , 8.19(1H, d, J=2.7 Hz), 8.55(1H, t, J=5.4 Hz) E0233 was prepared in a similar manner to that of E0231. white powder mp. 207-209°C IR (KBr) : 2966, 2933, 2871, 2750, 1606, 1566, 1549, 1512cm-l Mass (ESI+) : 395 (M+H) + 200MHz 1HNMR (DMS0-d6, d) : 1. 08-1. 22 (3H, m) , 2 . 97 , 3 . 29 ( 3H, s), 3.17-3.22(2H, m), 3.40-3.80(2H, m) , 3.78(3H, s), 4.14-4.20(2H, m) , 6.80,6.83(1H, s), 6.94-7.01(4H, m), 7.18-7.26(4H, m), 8.13(2H, brs) (E0234) E0234 was prepared in a similar manner to that of E0231. white powder mp. 129-142°C IR (KBr) : 3471, 3437, 2968, 2933, 1674, 1639, 1631, 1612, 1545, 1512cm-l Mass (ESI+) : 380 (M+H)+. 200MHz 1H NMR (DMS0-d6, d) : 1.15(6H, d, J=6.9 Hz), 3.16-3.22(2H, m) , 3.68(1H, m) , 3.79(3H, s) , 4.15-4.20(2H, m), 6.94-7.05(5H, m), 7.22(2H, d, J=8.8 Hz), 7.29(2H, d, J=8.9 Hz), 8.15(2H, brs) Example 235 (E0235) E0235 was prepared and in a similar manner to that of E0231. white powder mp. 186-189°C IR (KBr) : 3209, 3136, 2968, 2873, 1647, 1610, 1547, 1512cm-l Mass (ESI+) : 335 (M+H)+ 200MHz 1H NMR (DMS0-d6, d) : 3.19(2H, t, J=4 . 9 Hz) , 3.79(3H, s), 4.18(2H, t, J=4.9 Hz), 6.96-7.05(4H, m), 7.21(2H, d, J=8.8 Hz) , 7.29 (2H, d, J=9.0 Hz) , 7.32 (1H, s) , 8.16(2H, brs) (E0236) E0236 was prepared in a similar manner to that of E0231. white powder Mass (ESI+-) : 378 (M+H) + 200MHz 1H NMR (DMSO-d6, d) : 1.04 (4H, d, J=6.1 Hz) , 3.04 (1H, m), 3.14-3.22(2H, m), 3.80(3H, s), 4.15-4.21(2H, m), 6.93-7.05(5H, m) , 7.23(2H, d, J=8.6Hz), 7.31(2H, d, J=8 . 9 Hz), 8.15(2H, brs) Example 237 (E0237) E0237 was prepared in a similar manner to that of E0231. amorphous powder IR (KBr) : 3433, 3425, 3404, 3043, 3028, 3022, 2962, 1658, 1612cm-l Mass (ESI+) : 336 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 3.15-3.24(2H, m) , 3.88(3H, s) , 4.16-4.22(2H, m) , 6.94(1H, d, J=8.8 Hz), 7.01(2H, d, J=8 .7 Hz), 7.25(2H, d, J=8.7 Hz), 7.36(1H, s), 7.75(1H, dd, J=2.6,8.8 Hz), 8.10-8.30(2H, br), 8.20(1H, d, J=2.6 Hz) (E0238) E0238 was prepared in a similar manner to that of E0231. white powder mp. 156-161°C IR (KBr) : 2970, 1676, 1647, 1612, 1550, 1500cm-l Mass (ESI+) : 381 (M+H)+ 200MHz 1H NMR (DMS0-d6, d) : 1.16(6H, d, J=6.9 Hz), 3.15-3.24(2H, m) , 3.68(1H, m) , 3.88(3H, s) , 4.16-4.22(2H, m), 6.91-7.06(4H, m), 7.26(2H, d, J=8.7 Hz), 7.75(1H, dd, J=2.7,8.9 Hz), 8.18(1H, d, J=2.7 Hz), 8.22(2H, brs) (E0239) This compound was obtained according to a similar manner to that of E0231. IR (film): 3220.5, 1679.7, 1513.9, 1461.8, 1251.6, 1081.9, 1029.8, 837.0, 800.3 cm-1. (E0240) To a solution of E0267 (75.2 mg) in dichloromethane (1 ml) was added triethylamine (30.4 ml) and trimethylsilyl isocyanate (36.9 ml) at 0°C. After stirring for 5 hours, the mixture was quenched with water and extracted with dichloromethane. The combined organic layers were washed with brine, dried over magnesium sulfate, and evaporated under reduced pressure to give oil, which was purified with preparative TLC (1 mm, ethyl acetate) to give oil. The oil was crystallized from a mixture of isopropyl ether, ethyl acetate, and hexane to give E0240 as a white solid (39.1 mg, 51.2%) . NMR(DMS0-d6); 3.27-3.32(2H, m), 3.79(3H, s), 3.94(2H, t, J=5.6 Hz), 5.52(2H, brs, NH2), 6.15(1H, t, J=5.6 Hz, NH) , 6.94(2H, d, J=8.8Hz), 7.00(2H, d, J=8.9Hz), 7.07(1H, s) , 7.20(2H, d, J=8.8 Hz), 7.28(2H, d, J=8.9 Hz). MS(ESI+); 443.2(M+Na). IR(KBr), 1685.5, 1656.6cm-l. (E0241) E0241 was prepared from E0194 in a similar manner to that of E0240. white powder mp. 139-140°C IR (KBr) : 3458, 3342, 1691, 1647, 1604, 1572, 1529cm-l Mass (ESI+) : 404 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 3 . 28-3.36 (2H, m) , 3.87(3H, s) , 3.92-3.98(2H, m), 5.52(2H, brs), 6.15(1H, t, J=5.5 Hz), 6.88-6.98 (4H, m) , 7.10(1H, t, J=54.4 Hz) , 7.22(2H, d, J=8.7 Hz), 7.69(1H, dd, J=2.7,8.8 Hz), 8.14(1H, d, J=2.7 Hz) (E0242) E0242 was prepared in a similar manner to that of E0240. white powdermp. 108-113°C IR (KBr) : 3492, 3435, 3425, 3359, 3298, 1647, 1614, 1564, 1549, 1512cm-l Mass (ESI+) : 438 (M+H)+ 200MHz 1HNMR (DMS0-d6, d) : 1.08-1.22(3H, m) , 2.97,3.29(3H, s), 3.20-3.85(4H, m), 3.78(3H, s) , 3.94(2H, t, J=5.5 Hz), 5.53(2H, s),6.15(lH,t, J=5.6Hz) , 6.7 9,6.81(1H, s) , 6.92(2H, d, J=8.8 Hz) , 6.99(2H, d, J=8.9 Hz) , 7.17(2H, d, J=8.8 Hz) , 7.23(2H, d, J=8.9 Hz) (E0243) E0243 was prepared from E0234 in a similar manner to that of E0240. white powder mp. 144-145°C IR (KBr) : 3435, 3369, 3176, 2970, 1674, 1612, 1547, 1514cm-l Mass (ESI+) : 423 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.15(6H, d, J=6.9 Hz), 3.27-3.36(2H, m) , 3.68(1H, m) , 3.79(3H, s) , 3.90-3.97(2H, m), 5.53(2H, s), 6.15(1H, t, J=5.6Hz), 6.92(2H, d, J=8.7 Hz), 6.98(1H, s), 7.00(2H, d, J=8.9Hz), 7.18(2H, d, J=8 . 7 Hz), 7.28(2H, d, J=8.9 Hz) (E0244) E0244 was prepared from E0235 in a similar manner to that of E0240. white powder mp. 187-190°C IR (KBr) : 3379, 3201, 1649, 1614, 1579, 1527, 1506cm-l Mass (ESI+) : 378 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 3.27-3. 34 (2H, m) , 3.79(3H, s) , 3.94 (2H, t, J=5.5 Hz) , 5.52(2H, brs) , 6.14(1H, t, J=5.6Hz) , 6.94(2H, d, J=8.8 Hz), 7.00(2H, d, J=9.0 Hz), 7.17(2H, d, J=8.8 Hz), 7.24-7.31(3H, m) (E0245) E0245 was prepared in a similar manner to that of E0240. white powder mp. 136-137°C IR (KBr) : 3433, 3342, 3221, 1658, 1612, 1581, 1549, 1512cm-l Mass (ESI+) : 421 (M+H)+ 200MHz 1H NMR (DMS0-d6, d) : 1.04 (4H, d, J=6.2 Hz) , 3.03 (1H, m) , 3.27-3.36(2H, m) , 3.80(3H, s) , 3.90-3.97(2H, m) , 5.52(2H, s) , 6.14(1H, t, J=5.6 Hz) , 6.93(2H, d, J=8.8 Hz) , 6.97(1H, s), 7.01(2H, d, J=8.9 Hz) , 7.19(2H, d, J=8.8 Hz) , 7.30(2H, d, J=8.9 Hz) (E0246) E0246 was prepared in a similar manner to that of E0240. white powder mp. 173-176°C IR (KBr) : 3473, 3334, 1630, 1624, 1601, 1583cm-l Mass (ESI+) : 379 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 3. 27-3 . 36 (2H, m) , 3.88 (3H, s) , 3.92-3.98 (2H,m) , 5.52(2H, s) , 6.14 (1H, t, J=5.7Hz) , 6.93 (1H, d, J=8.8 Hz) , 6.97(2H, d, J=8.8 Hz) , 7.21(2H, d, J=8.8 Hz), 7.35(1H, s), 7.73(1H, dd, J=2.7,8.8 Hz) , 8.20(1H, d, J=2 . 7 Hz) (E0247) E0247 was prepared in a similar manner to that of E0240. white powder mp. 145-147°C IR (KBr) : 3367, 3174, 2972, 1689, 1674, 1610, 1566, 1502cm-l Mass (ESI+) : 424 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.16(6H, d, J=6.9 Hz), 3.28-3.37(2H, m) , 3.68(1H, m) , 3.88(3H, s), 3.92-3.98(2H, m), 5.52(2H, s), 6.15(1H, t, J=5.6Hz), 6.93(1H, d, J=8.7 Hz), 6.95(2H, d, J=8.8Hz), 7.02(1H, s) , 7.22(2H, d, J=8.8 Hz), 7.73(1H, dd, J=2.7,8.7 Hz), 8.19(1H, d, J=2.7 Hz) ] (E0248) E0248 was prepared in a similar manner to that of E0240. white powder mp. 150.8-151.0°C IR (KBr) : 3496, 3361, 3294, 1705, 1674, 1647, 1603, 1581, 1568, 1554, 1516cm-l Mass (ESI+) : 393 (M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 0.71-0.77(2H, m) , 0.85-0.92(2H, m), 1.92(1H, m), 3.27-3.37(2H, m), 3.76(3H, s), 3.92(2H, t, J=5.5Hz), 5.51(2H, s) , 6.14(1H, t, J=5.5Hz), 6.24(1H, s), 6.86-6.96(4H, m), 7.07-7.15(4H, m) Example 24 9 (E0249) This compound was obtained according to a similar manner to that of E0240 as an amorphous. NMR(CDC13) , 3.56-3.64(2H, m) , 3.94(3H, s) , 4.04(2H, t, J=4.9 Hz) , 4.50(2H, brs, NH2), 6.69(1H, s) , 6.76(1H, d, J=8.8 Hz) , 6.84(2H, d, J=8.8Hz), 7.12(2H, d, J=8.8Hz), 7.58(1H, dd, J=8.8, 2.8 Hz), 8.05(1H, d, J=2.8 Hz). MS(ESI+), 444.1 (M+Na)+. IR(KBr); 1650.8, 1608.3cm-l. LCMS(ESI+), 422.27(MH+). (E0250) This compound was obtained according to a similar manner to that of E0240 as a white powder. NMR(CDC13), 3.55-3.63(2H, m) , 3.93(3H, s) , 4.04(2H, t, J=5.1 Hz) , 4.55 (2H, brs, NH2) , 5.23 (1H, brt, J=5.4Hz, NH) , 6.67 (1H, s), 6.75(1H, t, J=55 Hz), 6.75(1H, d,' J=8.4 Hz), 6.88(2H, d, J=8.8 Hz), 7.13(2H, d, J=8. 8 Hz), 7.56(1H, d, J=8.4, 2.9 Hz), 8.04(1H, d, J=2.9 Hz). LCMS(ESI+), 404.39(MH+). IR(KBr) 1649cm-l MP, 141.5 - 142.1°C. This compound was obtained according to a similar manner to that of E0240 as a powder. NMR(CDC13), 3.56-3.64 (2H, m) , 3.82(3H, s) , 4.03(2H, t, J=5.0 Hz), 4.42(2H, brs), 6.65(1H, s) , 6.76(1H, t, J=55 Hz), 6. 79-6. 89 (4H, m) , 7.14 (2H, d, J=8.7 Hz) , 7.20 (2H, d, J=9.0 Hz) . MS(ESI+), 425(M+Na)+. To a solution of E0267 (15.3g) inethanol (75ml) andhydrogen chloride aqueous solution (IN, 220 ml) was added dropwise a solution of sodium cyanate (14.4 g) in water (300 ml) at 45°C over 5 minutes. After stirring at 45°C for 4 hours, the mixture was quenched with saturated sodium hydrogen carbonate aqueous solution and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, and evaporated to give powder. The powder was crystallized from ethyl acetate and hexane at room temperature ~ 70°C to give E0252 as a powder (12.628 g, 81.2%). The physical data of this compound was identical to previously obtained authentic sample. (E0253) To a solution of E0267 (200 mg) in methanol (1 ml) was added sodium methoxide methanol solution (5.2M, 0.1 ml) at room temperature. After stirring for 20 minutes, the mixture was evaporated to give residue. To the residue was added tetrahydrofuran, and the mixture was filtered and evaporated to give oil. The oil was dissolved in ethyl formate (2 ml) and stirred at room temperature overnight. The mixture was evaporated and purified with preparative TLC (Iran, 50% ethyl acetate/hexane) to give oil, which was crystallized from isopropyl ether, ethyl acetate, and hexane to give E0253 as a white powder (162.8 mg, 83%) . NMR(CDC13), 3.68-3.76 (2H, m) , 3.82(3H, s) , 4.06(2H, t, J=5.0 Hz) , 6.68(1H, s) , 6.8 0-6.89(4H, m) , 7.14(2H, d, J=8.7 Hz) , 7.22(2H, d, J=9.0 Hz), 8.22(1H, s). MS(ESI+), 428.2(M+Na). IR(KBr), 1660.4, 1614.lcm-1. Example 254 (E0254) To a solution of E0267 (800 mg) and triethylamine (0.7 ml) in dichloromethane (9ml) was added dropwise acetyl chloride (0.18 ml) at 0°C. After stirring at room temperature for 1 hour, the mixture was quenched with saturated sodium hydrogen carbonate aqueous solution and extracted with ethyl acetate (x3) . The combined organic layers were washed with hydrogen chloride aqueous solution (IN) , water, and brine, dried over magnesium sulfate, and evaporated to give oil, which was purified with column chromatography (Si02 100 ml, eluted with 50% ethyl acetate/hexane) to give oil. The oil was crystallized from a mixture of ethyl acetate and hexane at 50°C to give E0254 as a solid (768.6 mg, 94.8%). NMR(CDC13). 2.01(3H, s), 3.62-3.70(2H, m), 3.82(3H, s), 4.03 (2H, t, J=5.0Hz), 6.67(1H, s) , 6.80-6.91(4H, m) , 7.14(2H, d, J=8.7 Hz), 7.22(2H, d, J=9.0 Hz). MP; 109.8 - 110.2°C IR(KBr), 1649cm-l. MS(ESI+).442.1(M+Na). (E0255) This compound was obtained according to a similar manner to that of E0254 as an oil. NMR(CDC13), 3.69(3H, s), 3.65-3.73(2H, m), 3.82(3H, s), 3.86(2H, d, J=5.9Hz), 4.04(2H, t, J=5.1Hz), 6.67(1H, s), 6.80-6.89(4H, m) , 7.14(2H, d, J=8.5Hz), 7.22(2H, d, J=8. 9 Hz), MS(ESI+).515.2(M+Na). IR(KBr, 20727-10), 1722.1, 1710.6, 1673.9cm-l. (E0256) This compound was obtained according to a similar manner to that of E0254 as an oil (82 mg, 78%). MS(ESI+).458.2(M+Na). IR(Neat), 1699cm-l. NMR(CDC13); 3.54-3.62(2H, m), 3.69(3H, s), 3.82(3H, s), 4.02(2H,t), 6.67(1H, s) , 6.80-6.89(4H, m) , 7.13(2H, d, J=8. 9 Hz), 7.22(2H, d, J=9.0 Hz). (E0257) To a solution of E0275 (97.5 mg) and pyridine (0.14 ml) in dichloromethane (1ml) was added trif luoroacetic anhydride (60.6 ml) at 0°C. After stirring at room temperature overnight, the mixture was quenched with saturated sodium hydrogen carbonate aqueous solution (0.5 ml), filtered with chemelutelOOl (Varian) , andpurif iedwithpreparative TLC(1 mm, 50% ethyl acetate/hexane) to give E0257 as a solid (92. 5 mg, 7 6%). MS(ESI+), 496.1(M+Na). IR(KBr), 1705cm-l. NMR(CDC13),3.75-3.87 (2H, m), 3.82(3H, s), 4.10(4.8H, t) , 6.68(1H, s) , 6.83(2H, d, J=8.8 Hz), 6.88(2H, d, J=8.9 Hz) , 7.16(2H, d, J=8.8 Hz), 7.22(2H, d, J=8 . 9 Hz). (E0258) To a solution of E0327 (400mg) in THF (5ml) was added dropwise IN NaOH (2.5ml) at room temperature. The mixture was stirred overnight, and then quenched with IN HCl and CHC13. The organic layer was separated and water layer was extracted twice with CHC13. The combined organic layer was washed with water and brine, dried over Na2S04, and evaporated under reduced pressure. The residue was washed with IPE to give 273mg (70.7%) of E0258. IR (film): 2971.8, 1683.6, 1629.6, 1515.8, 1315.2, 1230.4, 1159-0, 1132.0, 977.7, 835.0cm-l. (E0259) E0259 was prepared in a similar manner to that of E0258. white powder Mass (ESI+) : 355 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 3.63-3.7 8 (2H, m) , 3.79 (3H, s) , 3.95-4.00(2H, m) , 4.86(1H, brs), 6.91(2H, d, J=8.7 Hz), 6.95(1H, s), 6.99(2H, d, J=8.9Hz), 7.16(2H, d, J=8.7Hz), 7.24(2H, d, J=8.9Hz), 12.88(1H, brs) (E0260) E0260 was prepared in a similar manner to that of E0258. white powder Mass (ESI+) : 356 (M+H)+ 200MHz 1H NMR (DMS0-d6, d) : 3.69-3.79(2H, m) , 3.88(3H, s) , 3.96-4.02(2H, m) , 4.87(1H, br) , 6.89-7.00(4H, m) , 7.20(2H, d, J=8.8 Hz) , 7.70(1H, dd, J=2.6,8.8 Hz) , 8.14(1H, d, J=2. 6 Hz), 12.97(1H, br) Example 261 (E0261) E0261 was prepared from E0109 in a similar manner to that of E0258. white powder Mass (ESI+) : 339(M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 2 .70 (2H, t, J=6. 9 Hz) , 3.59 (2H, t, J=6.9Hz), 3.79(3H, s) , 4.64(1H, brs), 6.96-7.03 (3H, m) , 7.12-7.28(6H, m) , 12.90(1H, br) (E0262) E0262 was prepared in a similar manner to that of E0258. white powder Mass (ESI+) : 454 (M+H)+ 200MHz 1H NMR (DMS0-d6, d) : 1.37 (9H, s) , 3.22-3.32 (2H, m) , 3.79(3H, s), 3.91-3.98(2H, m), 6.90(2H, d, J=8.7 Hz), 6.90-7.03(lH, overlapping), 6.95(1H, s), 6.99(2H, d, J=8.9 Hz), 7.16(2H, d, J=8.7 Hz), 7.24(2H, d, J=8.9 Hz) Example 263 E0263 was prepared in a similar manner to that of E0258. amorphous powder Mass (ESI+) : 455 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.37 (9H, s) , 3.22-3.32 (2H, m)., 3.88(3H, s), 3.93-3.98(2H, m) , 6.89-7.05(5H, m) , 7.20(2H, d, J=8.7Hz), 7.70(1H, dd, J=2 . 7, 8 . 8 Hz) , 8.14(1H, d, J=2 . 7 Hz), 12.98(1H, br) (E0264) E0264 was prepared from E0006 in a similar manner to that of E0258. white powder Mass (ESI+) : 340 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 2.71(2H, t, J=6.9 Hz), 3.56-3.64(2H, m) , 3.88(3H, s), 4.64(1H, br) , 6.92(1H, d, J=8.8 Hz), 7.03(1H, s), 7.16-7.28(4H, m), 7.72(1H, dd, J=8.8,2.7 Hz), 8.15(1H, d, J=2.7 Hz), 12.94(1H, br) (E0265) 4M HCl/AcOEt 0.4ml was added to a solution of E0378 (73mg) in AcOEt 1ml. The mixture was concentrated and dried in vacuo to give E0265 68.4mg as an amorphous powder. IR (neat) : 3440, 2960, 1739, 1707, 1691, 1674, 1647, 1624, 1614, 1566, 1549, 1533, 1500cm-l Mass (ESI+) : 400 (M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 2.73(2H, t, J=6.9 Hz) , 3.62 (2H, t, J=6.9 Hz), 3.89(3H, s), 6.94(1H, d, J=8.8 Hz), 7.19-7.32(5H, m) , 7.52-7.70(3H, m) , 7.80(1H, dd, J=8.8,2.7 Hz), 8.22-8.28(3H, m) (E0266) E0266 was prepared in a similar manner to that of E0265. oil IR (neat) : 3435, 2966, 2935, 1678, 1662, 1649, 1612, 1581, 1566, 1547, 1533, 1500cm-l Mass (ESI+) : 366 (M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 1.16(6H, d, J=6.9 Hz) , 2.72(2H, t, J=6.9 Hz), 3.54-3.75(3H, m), 3.89(3H, s), 6.93(1H, d, J=8.8 Hz), 7.05(1H, s), 7.13-7.35(4H, m), 7.76(1H, dd, J=2.7,8.8 Hz), 8.19(1H, d, J=2.7 Hz) (E0267) To a solution of E0275 (765 mg) in ethyl acetate (1.9 ml) was added a solution of hydrogen chloride in ethyl acetate (4N, 0.56 ml). The mixture was evaporated to give oil, which was crystallized from diisopropyl ether and ethyl acetate at 65°C to give E0267 as a solid (766.8 mg, 91.4%). NMR(CDC13), 3.30(2H, t, J=5.0 Hz), 3.79(3H, s) , 4.18(2H, t, J=5.0 Hz), 6.62(1H, s), 6.83-6.88(4H, m), 7.10(2H, d, J=8.8 Hz), 7.18(2H,'d, J=8.8 Hz). NMR(DMSO-d6), 3.19(2H, brs), 3.79(3H, s) , 4.18(2H, t, J=5.0 Hz), 6.96-7.01(4H, m), 7.08(1H, s), 7 . 23-7.29(4H, m) . MS(ESI+), 378.3(MH+, free). IR(KBr, 20727-2), 1612.2, 1513.9cm-l. (E0268) A mixture of POOH (30 g) , chloroacetonitrile (8.52 ml), potassium iodide (4.47 g), and potassium carbonate (14.9 g) in acetone (150 ml) was stirring under reflux at 80°C for 2 . 5 hours. After cooling to room temperature, the mixture was quenched with water (600 ml) and extracted with ethyl acetate (300 ml x 2, 150 ml) . The combined organic layers were washed with brine (300ml), dried over magnesium sulfate, and evaporated to give solid (36.34 g). The solid was recrysallized from diisopropyl ether (60 ml) and hexane (200 ml) at room temperature to give E0268 as a powder (31.5 g, 94%) . NMR(CDC13), 3.83(3H, s), 4.78(2H, s), 6.70(1H, s), 6.86-6.97(4H, m), 7.18-7.24(4H, m). IR(KBr), 2051.9cm-l. (E0269) E0269 was obtained according to a similar manner to that of E0268. white powder Mass (ESI+) : 346(M+H) + 200MHz 1HNMR (DMSO-d6, d) : 0.69-0.7 7(2H, m) , 0.86-0.96(2H, m), 1.92(1H, m), 3.76(3H, s), 5.16(2H, s), 6.30(1H, s), 6.93(2H, d, J=9.0 Hz) , 7.02(2H, d, J=8.8 Hz) , 7.10-7.21(4H, m) Example 27 0 s (E0270) This compound was obtained according to a similar manner to that of E0268 as a powder. NMR(CDC13), 3.95(3H, s), 4.78(2H, s) , 6.71(1H, s) , 6.76(1H, t, J=55 Hz), 6.76(1H, d, J=8.4 Hz), 6.96(2H, d, J=8. 9 Hz), 7.23(2H, d, J=8.9Hz), 7.53(1H, dd, J=8.4, 2.6Hz), 8.08(1H, d, J=2.6 Hz). MS(ESI + ),379(M+Na) . (E0271) This compound was obtained according to a similar manner to that of E0268. (E0272) This compound was obtained according to a similar manner to that of E0268. IR (film): 1612.2, 1482.9, 1234.2, 1162.8, 1132.0, 1095.3, 973.8, 835.0 cm-1. (E0273) This compound was obtained according to a similar manner to that of E0268. (E0274) This compound was obtained according to a similar manner to that of E0268. mp.96-99°C Mass;389(M+l) NMR(CDC13,5); 1.98(1H, t, J=6.1Hz), 3.29(3H, s), 3.83(3H, s), 3.93-4.01(2H, m), 4.06-4.11(2H, m), 6.86(2H, d, J=8.8 Hz), 6.88(2H, d, J=9.0 Hz), 6.93(1H, s), 7.14(2H, d, J=8.8 Hz), 7.23(2H, d, J=9.0 Hz) (E0275) To a suspension of lithium aluminum hydride (250 mg) in ether (14 ml) was added E0268 (1.38 g) in ether (5 ml) and tetrahydrofuran (1 ml) under ice-bath. The mixture was stirred at room temperature for 1 hour. Lithium aluminum hydride (50 mg) was added to the mixture under ice-bath., and then the mixture was stirred at room temperature for 1 hour. The mixture was quenched with water (0.3 ml), sodium hydroxide aqueous solution (15%, 0.3 ml), and water (0.9 ml), and then stirred at room temperature for 30 minutes. Magnesium sulfate and celite was added to the mixture, then the suspension was filtered and washed with ether. The filtrate was evaporated to give 1.307 g of oil. The oil purified with column chromatography (Si02, 100 ml, eluted with 20% methanol / chloroform (500 ml)) to give E0275 as an oil (1.156 g, 82.9%). NMR(CDC13), 3.09(2H, t, J=5.1Hz), 3.82(3H, s), 3.99(2H, t, J=5.1 Hz), 6.67(1H, s), 6.82-6.89 (4H, m), 7.14(2H, d, J-8.9 Hz), 7.23(2H, d, J=9.0 Hz). MS(ESI+), 378(MH+). Example 27 6 (E0276) To a solution of E0268 (27.43 g) in tetrahydrofuran (270 ml) was added borane methylsulfide complex (10M, 15 ml) at roomtemperature. Themixture was stirredat roomtemperature overnight. Then borane methylsulfide complex (7.5 ml) was added to the mixture. After stirring at room temperature overnight, the mixture was quenched with methanol (100 ml) and evaporated under reduced pressure to give oil. The oil was dissolved in a mixture of tetrahydrofuran (150 ml) and hydrochloric acid (6N, 100 ml), and then stirred at 40 ~ 50°C for 1 hour. To the mixture was added dropwise aqueous sodium hydroxide solution (30%, 80 ml), and then sodium hydrogen carbonate, and sodium chloride. The mixture was extracted with ethyl acetate (x4). The organic layer was evaporated to give oil (31.86 g) , which was purified with column chromatography (Si02, 1 L, eluted with 20% methanol/dichloromethane and concentrated ammonia/methanol/chloroform (0.025:1:4)) to give oil. A solution of hydrogen chloride in ethyl acetate (4N, 22 ml) was added to the solution of the oil in ethyl acetate (50 ml), and the mixture was evaporated to give E0276 as an amorphous (22.87 g, 69.4%). Example 277 (E0277) E0277 was prepared in a similar manner to that of E0276. white powder mp. 229-231°C IR (KBr) : 3084, 2960, 2885, 2800, 2731, 2563, 2519, 2482, 1606, 1576, 1516cm-1 Mass (ESI+) : 350 (M+H)+ 200MHz 1HNMR (DMS0-d6, d) : 0.69-0.77(2H, m) , 0.84-0.96(2H, m) , 1.93(1H, m), 3.14-3.22(2H, m) , 3.76(3H, s) , 4.14-4.20(2H, m), 6.26(1H, s), 6.94(4H, d, J=8 . 8 Hz), 7.14(4H, d, J=8.8 Hz), 8.21(2H, brs) (E0278) This compound was obtained according to a similar manner to that of E0276 without formation of hydrogen chloride salt (oil). NMR(CDC13), 3.09(2H, t, J=5.2 Hz), 3.94(3H, s), 3.99(2H, t, J=5.2Hz), 6.77(1H, t, J=54.9Hz), 6.67(1H, s), 6.74(2H, d, J=7.5 Hz) , 6.87(2H, d, J=8.9 Hz) , 7.15(2H, d, J=8.7 Hz), 7.55(1H, dd, J=8.9, 2.8 Hz), 8.09(1H, d, J=2.8 Hz). MS(ESI+), 361(MH+). (E0279) This compound was obtained according to a similar manner to that of E0276. / CI (E0280) This compound was obtained according to a similar manner to that of E0276. IR (film): 3423.0, 1612.2, 1469.5, 1240.0, 1164.8, 1132.0, 1095.4, 975.8, 836.9 cm-1. This compound was obtained according to a similar manner to that of E0276. mp.l04-106°C Mass;388(M+l) IR(KBr);1310cm-1 NMR(CDC13,5);3.09(2H, t, J=5.1Hz), 3.29(3H, s) , 3.83(3H, s), 3.99(2H, t, J=5.1Hz), 6.83(2H, d, J=8.8Hz), 6.88(2H, d, J=8.9 Hz) , 6.93(1H, s) , 7.13(2H, d, J=8.8 Hz) , 7.24(2H, d, J=8.9 Hz), (E0282) (P0015-1) Diethylazodicarboxylate 82.3mg was added to a solution of P0015 (lOOmg), P0015-1 (152mg), and triphenylphosphine 124mg in THF 2ml. After stirring at ambient temperature for 5 hours, Thereaction mixture was concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with AcOEt / CHC13 = 5% viscous oil to give E0282. Mass (ESI+) : 461 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.37 (9H, s) , 3.22-3.33 (2H, m) , 3.87(3H, s), 3.93-3.99(2H, m), 6.88-7.04 (5H, m), 7.10(1H, t, J=54.4Hz), 7.2M2H, d, J=8.7Hz), 7.69(1H, dd, J=2.7,8.8 Hz), 8.14(1H, d, J=2.7 Hz) Example 28 3 (E0283) E0283 was prepared from P0020 in a similar manner to that of E0282. white powder Mass (ESI+) : 482 (M+H)+ 200MHz 1H NMR (DMS0-d6, d) : 1.31 (3H, t, J=7 .1 Hz) , 1.37 (9H, s) , 3.22-3.32(2H, m) , 3.79(3H, s) , 3.91-3.98(2H, m) , 4.32(2H, q, J=7.1 Hz), 6.90(2H, d, J=8.7 Hz) , 6.95-7.06 (1H, overlapping), 6.99(2H, d, J=8.9Hz), 7.01(1H, s) , 7.17(2H, d, J=8.7 Hz), 7.25(2H, d, J=8.9 Hz) (E0284) E0284 was prepared in a similar manner to that of E0282. white powder Mass (ESI+) : 483 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.31 (3H, t, J=7 .1 Hz) ,1.37 (9H, s), 3.22-3.33(2H, m), 3.88(3H, s), 3.96(2H, t, J=5.7 Hz), 4.33(2H, q, J=7.1Hz) , 6.89-7.05(1H, overlapping), 6.92(1H, d, J=8.9 Hz), 6.93(2H, d, J=8.7 Hz), 7.05(1H, s), 7.21(2H, d, J=8.7 Hz) , 7.72 (1H, dd, J=2 . 7 , 8 . 9 Hz) , 8.15(1H, d, J=2 . 7 Hz) This compound was obtained according to a similar manner to that of E0282 as an oil. NMR(CDC13), 1.45(9H, s) , 3.50-3.58(2H, m) , 3.94(3H, s) , 4.02(2H, t, J=5.1Hz), 6.70(1H, s) , 6.75(1H, d, J=8.4Hz), 6.85(2H, d, J=8.9Hz), 7.15(2H, d, J=8.9Hz), 7.56(1H, dd, J=8.4, 2.9 Hz), 8.08(1H, d, J=2.9 Hz). MS(ESI+), 501.2(M+Na). \ (E0286) This compound was obtained according to a similar manner to that of E0282 as a powder. NMR(CDC13), 2.89(1H, d, J=10.4 Hz, NH), 3.23(3H, s), 3.67-3.78(1H, m) , 3.81(3H, s) , 3.99(1H, dd, J=9.2, 6.4 Hz), 4.22(1H, dd, J=9.2, 5.0Hz), 6.67(1H, s) , 6.8K2H, d, J=8. 9 Hz) , 6.86(2H, d, J=6.0Hz), 7 .10-7.29(13H, m), 7.4 9-7.54(6H, m) . MS(ESI+), 678.4(MH+). (E0287) This compound was obtained according to a similar manner to that of E0282 as an oil. NMR(CDC13), 1.28(3H, d, J=6.6Hz), 1.45(9H, s), 3.82(3H, s), 3.92(2H, d, J=4.1 Hz), 3. 90-4.14(1H, m), 6.67(1H, s) , 6.84(2H, d, J=8.9 Hz), 6.86(2H, d, J=9.0 Hz), 7.13(2H, d, J=8.9 Hz), 7.23(2H, d, J=9.0 Hz). MS(ESI+), 514.2(M+Na). (E0288) This compound was obtained according to a similar manner to that of E0282 as an oil. NMR(CDC13), 1.28(3H, d, J=6.6Hz), 1.45(9H, s), 3.82(3H, s), 3.92(2H, d, J=4.1 Hz), 3.90-4.14(1H, m), 6.67(1H, s), 6.84(2H, d, J=8.9Hz), 6.86(2H, d, J=9.0Hz), 7.13(2H, d, J=8.9 Hz), 7.23(2H, d, J=9.0 Hz). HS(ESI+), 514.2(M+Na). (E0289) 4M HCl/AcOEt 1ml was added to a solution of E0282 (129mg) in AcOEt 1ml, and the mixture was stirred at ambient temperature for lhour * The supernatant was removed by decantation. The residual oily solid was washed with AcOEt 1ml by decantation. To the residue was added acetone 2ml, and oily residual solid became white powder on stirring. This was stirred at ambient temperature for 20minutes. The precipitates were collected and washed with acetone to give E0289 (91.4mg) as a white powder. IR (neat) : 2964, 1705, 1668, 1660, 1614, 1581, 1566, 1531, 1512cm-l Mass (ESI + ) : 361 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 3.11-3.23(2H, m) , 3.87(3H, s) , 4.12-4.28 (2H, m) , 6. 90-7 . 02 (4H, m) , 7.11(1H, t, J=54.3Hz) , 7.26(2H, d, J=8.6 Hz) , 7.71(1H, dd, J=2.7,8.8 Hz) , 8.14 (1H, d, J=2.7 Hz), 8.24(2H, brs) (E0290) This compound was obtained according to a similar manner to that of E0289 as a white powder. NMR(DMS0-d6), 3.17-3.21(2H, m), 3.95(3H, s), 4.19(2H, t, J=5.0 Hz), 6.93(1H, d, J=8.8 Hz), 7.00(2H, d, J=8.8 Hz), 7.15(1H, s), 7.28(2H, d, J=8.8.Hz), 7.76(1H, dd, J=8.8, 2.6 Hz), 8.18 (1H, d, J=2.6 Hz). MS(ESI+), 379.1(MH+). IR(KBr), 1612.2cm-l. (E0291) This compound was obtained according to a similar manner to that of E0289 as a white powder. NMR(DMS0-d6) , 2.60(3H, s) , 3 . 28-3.33(2H, m) , 3.79(3H, s), 4.25(2H, t, J=4.7 Hz), 7.04-6.96(4H, m), 7.09(1H, s), 7.22-7.3K4H, m) . MS(ESI-), 426.2 (M+C1)+. IR(KBr); 1610.2, 1515.8cm-l. MP; 189 - 189.2°C. Example 292 (E0292) This compound was obtained according to a similar manner to that of E0289 as a white amorphous. NMR(DEMS0-d6) ,1.04(3H, d, J=6.0 Hz), 3.5-3.7(lH, m), 3.79(3H, s), 3.98(1H, dd, J=10.1, 6.9 Hz), 4.11(1H, dd, J=10.1, 6.5Hz), 6.96-7.04(4H, m) , 7.09(1H, s) , 7.22-7.31(4H, m) . MS(ESI + ), 392.2(MH+) . (E0293) This compound was obtained according to a similar manner to that of E0289 as a white amorphous. NMR(DEMSO-d6),1.04(3H, d, J=6.0 Hz), 3.5-3.7(lH, m), 3.79(3H, s), 3.98(1H, dd, J=10.1, 6.9 Hz), 4.11(1H, dd, J=10.1, 6.5Hz), 6.96-7.04(4H, m) , 7.09(1H, s) , 7.22-7.31(4H, m) . MS(ESI+), 392.2(MH+). IR(Neat) 1612.2cm-l. Example 2 94 (E0294) This compound was obtained according to a similar manner to that of E0289 as a white powder. NMR(DMS0-d6); 2.84-3.20(4H, m), 3.88(3H, s), 6.93(1H, d, J=8.9Hz), 7.19(1H, s), 7 . 30-7.36(4H, m) , 7.86(1H, dd, J=8.9, 2.7 Hz), 8.19(1H, d, J=2.7 Hz). MS(ESI+); 363.3(MH+). IR(KBr); 1612.2, 1500.3cm-l. \ (E0295) A mixture of P0012 (0.5 g) , chloroacetonitrile (0.2 ml), potassium iodide (525 mg) , and potassium carbonate (437 mg) in N,N-dimethylformamide (6 ml) was stirring at 75°C for 6 hours. After cooling to room temperature, the mixture was quenched with water, and extracted with ethyl acetate (x3). The combined organic layers were washed with water (x3) and brine, dried over magnesium sulfate, and evaporated to give E0295 as a solid (631.6 mg, 112%). NMR(CDC13), 3.83(3H, s), 4.77(2H, s) , 6.69(1H, s) , 6.76(1H, t, J=55 Hz), 6.96-6.86(4H, m) , 7.18-7.24(4H, m) . MS(ESI+), 378.1(M+Na). (E0296) This compound was obtained according to a similar manner to that of E0295 as an oil. NMR(CDC13) ; 1.63(1H, t, J=5.2Hz) , 1. 99-2 .11 (2H, m) , 3.82(3H, s), 3.82-3.91(2H, m), 4.12(2H, t, J=6.0 Hz), 6.67(1H, s), 6.84(2H, d, J=8.8 Hz), 6.87(2H, d, J=8.9 Hz), 7.13(2H, d, J=8.8 Hz), 7.32(2H, d, J=8.9 Hz). IR(Neat); 1612, 1514cm-l. MS(ESI + ); 393.KMH+), 415.1(M+Na). (E0297) This compound was obtained according to a similar manner to that of E0205 as an oil. NMR(CDC13);3.03(3H, s) , 3.83(3H, s) , 4.97(2H, s) , 6.70(1H, s), 6.88(2H, d, J=9.0 Hz), 7.01(2H, d, J=8.8 Hz), 7.17-7.26(4H, m). IR(KBr); 1612.2, 1513.9 cm-1. MS(ESI+),449.1(M+Na). (E0298) This compound was obtained according to a similar manner to that of E0295 as a white solid. NMR(DMS0-d6), 3.65-3.73(2H, m), 3.79(3H, s), 3.98(2H, t, J=4.7 Hz), 4.87(1H, t, J=5.4 Hz), 6.93(2H, d, J=8.7 Hz), 7.00(2H, d, J=8.9Hz), 7.07(1H, s) , 7.19(2H, d, J=8.7Hz), 7.28(2H, d, J=8.9 Hz). MS(ESI+), 401.2(M+Na). IR(KBr); 1610.3, 1511.9cm-l. (E0299) This compound was obtained according to a similar manner to that of E0295 as a white solid. NMR(CDC13), 2.01(1H, t, J=6.1Hz), 3.82(3H, s), 3.93-4.10(4H, m) , 6.66(1H, s), 6.76(1H, t, J=55.1Hz), 6.85(2H, d, J=8.7 Hz) , 6.87(2H, d, J=9.0 Hz) , 7.15(2H, d, J=8.7 Hz) , 7.21(2H, d, J=9.0 Hz). MS(ESI+); 383.2(M+Na). IR(KBr); 1610.3, 1513.9, 1454.1cm-l. (E0300) This compound was obtained according to a similar manner to that of E0295 as a white powder. NMR(DMS0-d6); 3.78(3H, s) , 4.43(2H, s) , 6.80-7.53(12H, m, NH2) , MS(ESI+);396.3(M+Na)+. IR(KBr); 1681.6, 1606.4cm-l. (E0301) Alkylation of this compound was achieved by a similar manner to that of E0295 to give salt free compound as an oil. Hydrogen chloride salt formation was achieved successively by a similar manner to that of E0172 to give E0301 as a white powder (498.7 mg, 49.6%). NMR(DMS0-d6), 3.69(2H, t, J=5.0Hz), 3.88(3H, s) , 3.99(2H, t, J=5.0 Hz) , 6.92(1H, d, J=8.7 Hz) , 6.96(2H, d, J=8.8 Hz) , 7.13(1H, s) , 7.23 (2H, d, J=8 .8 Hz) , 7.53 (1H, dd, J=8.7, 2.9 Hz), 8.18(1H, d, J=2.9 Hz). MS(ESI+), 402.1(M+Na)+, (Free). IR(Neat), 1614, 1552cm-l. (E0302) This compound was obtained according to a similar manner to that of E0295 as a white solid. NMR(CDC13) ; 3.88 (3H, s) , 4.4 5 (2H, s) , 6.92 (1H, d, J=8.9Hz) , 6.96(2H, d, J=8.8Hz), 7.14(1H, s) , 7.26(2H, d, J=8.8Hz), 7.41(1H, brs, NH2), 7.56(1H, brs, NH2) , 7.76(1H, dd, J=8.9, 2.5 Hz), 8.18(1H, d, J=2.5 Hz). MS(ESI+); 415.1(M+Na). IR(KBr); 1693.2, 1608.3cm-l. (E0303) This compound was obtained according to a similar manner to that of E0295 as an oil. NMR(CDC13); 3.94(3H, s), 3.94-4.14(4H, m), 6.68(1H, s), 6.74(1H, d, J=8.7Hz), 6.86(1H, t, J=55.0Hz), 6.88(2H, d, J=8.9Hz), 7.16(2H, d, J=8.9Hz), 7.53(1H, dd, J=2.6, 8.7 Hz) , 8.08(1H, d, J=2.6 Hz) . MS(ESI+); 384.2(M+Na). IR(KBr), 1805.1, 1612.2cm-l. (E0304) This compound was obtained according to a similar manner to that of E0295 as a white powder. NMR(DMSO-d6); 3.88(3H, s) , 4.44(2H, s) , 6.98-9.89(4H, m) , 7.10(1H, t, J=54.3Hz), 7.24(2H, d, J=8.8Hz), 7.39(1H, brs, NH2), 7.54(1H, brs, NH2), 7.70(1H, dd, J=8.9, 2.8 Hz), 8.14 (1H, d, J=2.8 Hz) . MS(ESI-); 373 (M-H)+. IR(KBr); 1662.3, 1610.3cm-l. (E0305) This compound was obtained according to a similar manner to that of E0298. IR (film): 3388.3, 1494.6, 1236.2, 1160.9, 1133.9, 1095.4, 975.8, 833.1 cm-1. Example 306 —-—o (E0306) This compound was obtained according to a similar manner to that of E0295. Mass;384(M+l) (E0307) To a suspension of lithium aluminum hydride (250 mg) in ether (5 ml) was added E0295 (630 mg) in tetrahydrofuran (1 ml) under ice-bath. After stirring at room temperature for 1 hour, the mixture was quenched with water (0.125 ml), sodium hydroxide aqueous solution (15%, 0.125 ml), and water (0 . 37 5 ml) , and then stirred at room temperature for 30 minutes. Magnesium sulfate and celite was added to the mixture, then the suspension was filtered and washed with ether. The filtrate was evaporated to give 0.5 g of oil. The oil was purified with column chromatography (Si02, 50 ml, eluted withmethanol / dichloromethane / concentrated ammonia water (1/10/0.05)) to give oil (300 mg). The oil was dissolved in ethyl acetate and added a solution of hydrogen chloride in ethyl acetate (4N, 1.6 ml) . The mixture was evaporated to give oil, which was crystallized from methanol and diisopropyl ether to give E0307 as a powder (300 mg, 42.7%) . NMR(DMSO-d6), 3.20(2H, t, J=4.9Hz), 3.78(3H, s) , 4.16(2H, t, J=4.9 Hz), 6.85(1H, s), 6.94-7.01(4H, m), 7.08(1H, t, J=54.6 Hz), 7.20-7.26(4H, m). MS(ESI+), 360.3(MH+, free). IR(KBr, 20727-7), 1612, 1513.9 cm-1. (E0308) This compound was obtained according to a similar manner to that of E0307. IR (film): 3401.8, 1610.3, 1511.9, 1469.5, 1240.0, 1162.9, 1130.1, 975.8, 827.3 cm-1. (E0309) A mixture of POO 11 (200 mg) , Chloromethyl sulfonic acid sodium salt (274 mg) , potassium iodide (298 mg) , and potassium carbonate (248 mg) in l-methyl-2-pyrrolidinone (2 ml) was stirring at 150°C overnight. After cooling to room temperature, the mixture was poured into a mixture of aqueous hydrogen chloride solution (1 N) , brine, and ethyl acetate. The aqueous layer was separated and extracted with ethyl acetate (x3) . The combined organic layers were dried over magnesium sulfate, and evaporated under reduced pressure to give oil. The oil was purified with column chromatography (Si02 100 ml, eluted with 15% methanol / dichloromethane) to give E0309 as a brown amorphous (154.3 mg, 60%) MS(ESI-); 427.1(M-H). NMR(DMSO-d6), 3.79(3H, s) , 4.52(2H, s) , 7.00(2H, d, J=9.0 Hz), 7.01(2H, d, J=8.9Hz), 7.07(1H, s) , 7.18(2H, d, J=9.0 Hz), 7.27(2H, d, J=8.9 Hz). (E0310) To a solution of POOH (l-0g) in DMF (10ml) under water cooling was added portionwise NaH (60%in Oil, 144mg) and stirred for 1 hour. After then, III (787mg) was added and the reaction mixture was stirred at 50oC for 5 hours. The mixture was quenched with water and extracted twice with EtOAc. The organic layer was washed three times with water and once with brine, dried over MgS04, filtered and evaporated under reduced pressure. The residue was column chroruatographed on silica gel (50ml) to give 803mg (55%) of E0310 as a oil. (E0311) This compound was obtained according to a similar manner to that of E0310. (E0312) Themixtureof E0310 (800mg) and cHCl (lOOul) inEtOH (10ml) was stirred at room temperature for 3 hours. After addition of aqueous sodium bicarbonate, the mixture was evaporated, and extracted twice with EtOAc. The organic layer was washed with water and brine, dried over MgS04, filtered and evaporated under reduced pressure. The residue (710mg) was column chromatographed on silica gel (50ml) to give 570mg (93%) of E0312. IR (film): 3409.5, 1612.2, 1513.9, 1467.6, 1243.9, 1162.9, 1130.1, 835.0, 835.0 cm-1. (E0313) This compound was obtained according to a similar manner to that of E0312. mp: 122.3-122.5°C IR (film): 3399.9, 1612.2, 1513.9, 1456.0, 1251.6, 1174.4, 1083.8, 1033.7, 836.9, 800.3 cm-1. (E0314) 60% Sodium hydride 39.7mg was added to a solution of POOH (255mg) in DMF 1.5ml. The mixture was stirred at ambient temperature for lhour. To this was added ethyl bromoacetate 153mg. The reaction mixture was stirred at ambient temperature for lhour, and then quenched by adding saturated ammonium chloride solution, and whole mixture was extracted tfith AcOEt. The organic layer was washed with H20, aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with AcOEt / n-hexane = 30% to give E0314 (217mg) as an oil. ^ass (ESI+) 421(M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 1.94 (3H, t, J=7 .1 Hz) , 3.79(3H, s), 4.15(2H, q, J=7 .1 Hz), 4.79(2H, s) , 6.92(2H, d, J=8.8 Hz) , 6.99(2H, d, J=8.9 Hz) , 7.09 (1H, s) , 7.20 (2H, d, J=8.8 Hz), 7.28 (2H, d, J=8.9 Hz) 1M solution of diisobutylaluminum hydride in toluene 0.5ml was added dropwise to a solution of E0314 (98mg) in THF 3ml at -50°C. The mixture was stirred at -50°C for Ihour, then at 5°C for Ihour. Additional 1M solution of diisobutylaluminum hydride in toluene 0.5ml was added dropwise. After stirring at 5°C for one more hour, the reaction was quenched by adding 10% aqueous potassium sodium tartaric acid salt, and the mixture was filtered through a celite pad. The filtrate was extracted with AcOEt. The organic layer was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by preparative thin layer silica gel chromatography developed by AcOEt / n-hexane = 60%. The separated silica gel was extracted with 10% MeOH/CHC13 and the solvent was evaporated in vacuo to give E0315 (54 . 5mg) as an oil, which became solid on standing. IR (KBr) : 3431, 2931, 1612, 1564, 1549, 1512cm-l Mass (ESI + ) : 379 (M+H)+ 4 00MHz 1H NMR (DMSO-d6, d) : 3. 67-3. 72 (2H, m) , 3.7 9 (3H, s) , 3.84-3.99(2H, m) , 4.87(1H, t, J=5.4 Hz) , 6.93(2H, d, J=8 . 7 Hz), 7.00(2H, d, J=8.9Hz), 7.10(1H, s), 7.19(2H, d, J=8.7 Hz), 7.27(2H, d, J=8 . 9 Hz) 60% Sodium hydride 52mg was added to a solution of P0020 (200mg) in DMF 2ml under ice bath cooling. The mixture was stirred at same temperature for 30minutes. To this was added bromoacetic acid 90.3mg. The reaction mixture was stirred at ambient temperature for 2hours, and then quenched by adding slM HC1 3ml. H20 3ml and diisopropyl ether 2ml were added and the mixture was stirred in an ice bath for 30minutes . The precipitates were collected and washed with H20 and diisopropyl ether to give E0316 (231. 2mg) as a white powder Mass (ESI + ) : 397 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.31(3H, t, J=7 .1 Hz) , 3.7 9 (3H, s), 4.32(2H, q, J=7.1Hz), 4.68(2H, s), 6.88(2H, d, J=8.8 Hz), 7.00(2H, d, J=8.9Hz), 7.02(1H, s) , 7.18(2H, d, J=8.8 Hz), 7.26(2H, d, J=8. 9 Hz), 13.05(1H, brs) (E0317) E0317 was prepared in a similar manner to that of E0316. white powder Mass (ESI+) : 398 (M+H) + 200MHz 1H NMR (DMSO-d6, d) : 1.31 (3H, t, J=7 .1 Hz) , 3.88 (3H, s), 4.33(2H, q, J=7.1Hz), 4.70(2H, s), 6.92(2H, d, J=8.8 Hz), 6.89-7.00(lH, m) , 7.06(1H, s), 7.22(2H, d, J=8.8 Hz), 7.73 (1H, dd, J=2.8,8.8Hz) , 8.15(1H, d, J=2.8Hz) , 13.04 (1H, brs) (E0318) E0318 was obtained according to a similar manner to that of E0316. oil Mass (ESI+) : 365 (M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 0.70-0.93(4H, m) , 1.70-2.00 (1H, m) , 3.7 6(3H, s) , 4.66(2H, s) , 6.25(1H, s) , 6.85(2H, d, J=8.9 Hz) , 6.92 (2H, d, J=9.0Hz) , 7 . 0 6-7 .16 (4H, m) , 13.00 (1H, brs) (E0319) To a suspension of sodium borohydride 19.1mg in THF 2ml was added boron trifluoride diethyl etherate 89.5mg dropwise under ice bath cooling 2.5eq. The mixture was stirred at same temperature for 30minutes. E0316 (lOOmg) was added in one portion and the mixture was stirred at ambient temperature for 5hours. 1M HC1 5ml was added and the mixture was stirred at ambient temperature for 30minutes. Themixture was extracted with AcOEt. The organic layer was washed with saturated aqueous sodiumbicarbonate solution and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was crystallized from diisopropyl ether to give E0319 (68.9mg) as a white powder. Mass (ESI + ) : 383 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 1.31(3H, t, J=7.1 Hz), 3.65-3.73(2H, m) , 3.79(3H, s) , 3.94-4.00(2H, m) , 4.32(2H, q, J=7.1 Hz) , 4.87 (1H, t, J=5.5 Hz) , 6.91(2H, d, J=8.8 Hz) , 6.99(2H, d, J=8.9 Hz) , 7.01(1H, s) , 7.17(2H, d, J=8.8 Hz) , 7.25 (2H, d, J=8.9 Hz) (E0320) E0320 was prepared in a similar manner to that of E0319. white powder Mass (ESI+) : 384 (M+H)+ 200MHz 1H NMR (DMS0-d6, d) : 1.31(3H, t, J=7.1 Hz), 3.65-3.74(2H, m) , 3.88(3H, s) , 3.96-4.02(2H, m) , 4.33(2H, q, J=7.1 Hz), 4.87(1H, t, J=5.4 Hz), 6.89-6.96(3H, m), 7.05(1H, s), 7.21(2H, d, J=8.7Hz), 7.72(1H, dd, J=2.7,8.8 Hz), 8.14(1H, d, J=2.7 Hz) o (E0321). E0321 was prepared in a similar manner to that of E0319. white powder mp. 142-144°C IR (KBr) : 3246, 2924, 1612, 1566, 1547, 1516cm-l Mass '(ESI + ) : 351 (M+H) + 200MHz 1HNMR (DMS0-d6, d) : 0. 68-0 . 77 (2H, m) , 0.85-0.95 (2H, m), 1.92(1H, m) , 3. 64-3.73(2H, m), 3.76(3H, s) , 3.96(2H, t, J=4.9 Hz), 4.85(1H, t, J=5.5 Hz), 6.24(1H, s), 6.85-6.96(4H, m), 7.05-7.17(4H, m) (E0322) E0322 was prepared in a similar manner to that of E0319. white powder mp. 228-231°C IR (KBr) : 3082, 2958, 2885, 2802, 2733, 2480, 1606, 1572, 1512cm-l Mass (ESI+) : 350 (M+H) + 200MHz 1HNMR (DMS0-d6, d) : 0.69-0.7 7 (2H, m) , 0 . 83-0. 96 (2H, m) , 1.93(1H, m) , 3.14-3.22(2H, m) , 3.76(3H, s) , 4.14-4.20 (2H, m), 6.27(1H, s), 6.93(4H, d, J=8.8 Hz), 7.14(4H, d, J=8.8 Hz), 8.24(2H, brs) (E0323) A solution of sodium sulfite 84.2mg in H20 1ml was added to a solution of P0022 (258. lmg) in EtOH 3ml and stirred at 70°C for 2hours. At which time, white precipitates were appeared and H20 1ml was added to dissolve the precipitates . The mixture was stirred at 80°C overnight to give a clear solution. This was stirred at 80°C further for 28hours. The reaction mixture was acidified by 1M HC1 0. 7ml, concentrated and dried under vacuo. The residue was dissolved in CHC13, dried over magnesium sulfate, all of unsoluble matter was filtered off, and concentrated in vacuo to give E0323 (245mg) as an amorphous powder. Mass (API-ES negative) 425(M-H)+ 200MHz 1HNMR (DMSO-d6, d) : 2 . 61-2 . 69 (2H, m) , 2 . 7 8-2 . 91 (2H, m) , 3.7 9(3H, s) , 7.00(2H, d, J=8.9Hz), 7.12(1H, s) , 7.17 (2H, d, J=8.6 Hz), 7.22 (2H, d, J=8.6 Hz), 7.29 (2H, d, J=8.9 Hz) (E0324) E0324 was prepared from P0023 in a similar manner to that of E0323. amorphous powder Mass (API-ES negative) : 426 (M-H)+ 200MHz 1HNMR (DMSO-d6, d) : 2 . 61-2 . 69 (2H, m) , 2.83-2.92 (2H, m) , 3.88(3H, s) , 6.92(1H, d, J=8.8 Hz), 7.17 (1H, s) , 7.23(4H, s), 7.75(1H, dd, J=8.8,2.7 Hz), 8.20(1H, d, J=2.7 Hz) DMF 41mg was added to a solution of E0319 (239mg) in thionyl chloride 0.6ml and the mixture was stirred at 50°C for 30minutes. The reaction mixture was concentrated in vacuo. To the residue was added toluene 3ml, and concentrated in vacuo. The residue was dissolved in THF 10ml and was added dropwise to a solution of 28% aqoueous ammonium hydroxide solution 0. 5ml and tetrabutylammonium hydrogensulf ate 19mg in THF 4ml under ice bath cooling. After stirring at ambient temperature for 30minutes, the reaction mixture was partitioned between AcOEt and aqueous sodium chloride solution. The organic layer was washed with aqueous sodium chloride solution, dried over magnesiumsulfate. The residue was purified by silica gel column chromatography eluted with MeOH / CHC13 = 2%, 5%. Pure fraction was collected and concentrated in vacuo. The residual solidwas recrystallized fromEtOH-diisopropyl ether to give E0325 (72.6mg) as a white powder. mp. 131-132°C IR (KBr) : 3354, 3184, 3126, 1707, 1693, 1676, 1647, 1564, 1549, 1516cm-l Mass (ESI+) : 426 (M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 2.95-3.04 (2H, m) , 3.21-3.30 (2H, (E0326) E0326 was prepared in a similar manner to that of E0325. white powder mp. 139-140°C IR (KBr) : 3230, 3132, 1610, 1568, 1527, 1500cm-l Mass (ESI+) : 441 (M+H)+ 200MHz 1H NMR (DMS0-d6, d) : 2.58 (3H, s) , 2 . 90-3.00(2H, m) , 3. 25-3.33(2H, m) , 3.88(3H, s), 6.93(1H, d, J=8.9Hz), 6.97(1H, brs), 7.19(1H, s) , 7.26(2H, d, J=8.3Hz), 7.34(2H, d, J=8.3 Hz), 7.77(1H, dd, J=8.9,2.8 Hz), 8.19(1H, d, J=2.8 Hz) (E0327-0) (E0327-1) (E0327) A mixture of E0327-0 (800mg) and E0327-1 , methyl (triphenylphosphoranylidene)- acetate (850mg) in toluene (10ml) was stirred under reflux condition for 5 hrs. The mixture was evaporated under reduced pressure and column chromatographed on silica gel (50ml, Hex:EtOAc=5:1) to give 795mg(85.5%) of E0327. IR (film): 1718.3, 1637.3, 1513.9, 1241.9, 1166.7, 1132.0, 977.7, 837.0cm-l (E0328) To a suspension of E0258 (180mg) in toluene (5ml) was adde thionylchloride (0.17ml) at room temperature. The reaction mixture was stirred at 100 °C for 5 hours until the mixture become clear solution. After then, the mixture was evaporated under reduced pressure, (become solid) THF was added, and then aqueous NH3 (37%) was added. The mixture was stirred for 1 hour, and quenched with water, and extracted twice with EtOAc. The combined organic layer was washed with sat.NaHC03, water and brine, dried over Na2S04, filtered and evaporated under reduced pressure to give 170mg (95%) of E0328 as a powder. IR (KBr): 3347.8, 1671.9, 1606.4, 1513.9, 1467.6, 1388.5, 1236.2, 1164.8, 1132.0, 979.7, 837.0cm-l. (E0329) T a suspension of E0258 (200mg) in toluene (4ml) was added thionylchloride (0.19ml) at room temperature. The reaction mixture was stirred at 10°C for 5 hours until the mixture become clear solution. After then, the mixture was evaporated under reduced pressure, (become solid) THF was added, and then Me2NH (116mg) was added. The mixture was stirred for 1 hour, and quenched with water, and extracted twice with EtOAc. The combined organic layer was washed withsat.NaHC03, waterandbrine, driedoverNa2S04, filtered and evaporated under reduced pressure to give 45mg (21%) of E0329 as a powder. Filtrate (58mg). mp: 118-12CTC IR (film): 1650.8, 1608.3, 1511.9, 1469.5, 1240.0, 1159.0, 1133.9cm-l. (E0330) A mixture of E0328 (125mg) and Pd/C (lOOmg) in EtOH (10m) was stirred under H2 atmosphere for 3.0 hours. After filtration, a filtrate was evaporated under reducedpressure. The residue was dissolved in EtOH and filtered with syringe driven filter, and evaporated to give 85mg of E0330. IR (KBr): 3342.0, 1670.0, 1511.9, 1240.0, 1160.9, 1130.1cm-l. (E0331) A mixture of E0138 (300mg) and MeSNa (72mg) in DMF (6ml) was heated at 70°C for 5 hours. After cooling, the reaction mixture was partitioned between EtOAc and water. The aqueous layer was separated and extracted ' with EtOAc. The combined organic layer was washed with water (twice) and brine, dried over Na2S04, filtered and evaporated. The residue was column chromatographed on silica gel to give 270mg (quant) of E0331. (E0332) E0332 was prepared from E0141 in a similar manner to that of E0331. oil Mass (ESI + ) : 408 (M+H) + 200MHz 1H NMR (DMSO-d6, d) : 1. 73-1. 89 (2H, m) , 2.03 (3H, s) , 2.40-2.52(2H, m) , 2 .62-2.70(2H, m) , 3.88(3H, s) , 6.92(1H, d, J=8.8 Hz), 7.18(1H, s) , 7.24(4H, s) , 7.76(1H, dd, J=8.8,2.7 Hz), 8.18(1H, d, J=2.7 Hz) i-(E0333) This compound was obtained according to a similar manner to that of E0331. (E0334) This compound was obtained according to a similar manner to that of E0331. Example 335 (E0335) This compound was obtained according to a similar manner to that of E0331 (E0336) This compound was obtained according to a similar manner to that of E0331. A mixture of E0331 (250mg) and mcpba (165mg) in CH2C12 was stirred under ice-cooling for 1 hour, and then mcpba (55mg) was added. After stirring for 1 hour under ice cooling, the reaction mixture was partitioned between CHC13 and sat.NaHC03. The organic layer was separated , washed with sat .NaHC03, water andbrine, driedover Na2S04 , filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel (Hex/EtOAc) to give 141mg (52%) of E0337. IR (film): 1511.9, 1303.6, 1240.0, 1130.1cm-l. Oxide: FR267958 NMR (CDC13) : 2.599(s, 3H) , 2.85-3.21(m, 4H) , 3.828(s, 3H) , 6.721(s, 1H), 6.872(d,J=9.0Hz,2H), 7.141(s, 4H), 7.179(d,J=9.0Hz, 2H). MS: (M+Na)+ 431.1 (M110092-2) (E0338) This compound was obtained according to a similar manner to that of E0337. IR (film): 1511.9, 1469.5, 1311.4, 1282.4, 1236.2, 1126.2, 973.9, 823.5, 759.8 cm-1. Example 339 (E0339) This compound was obtained according to a similar manner to that of E0337. IR (film): 1511.9, 1469.5, 1311.4, 1282.4, 1236.2, 1128.2, 973.9, 823.5, 759.8cm-l. t o (E0340) This compound was obtained according to a similar manner to that of E0337. IR(film): 1673.9, 1616.1, 1498.4, 1477.2, 1467.6, 1390.4, 1307.5, 1290.1, 1240.0, 1160.9, 1132.0, 971.9, 756.0cm-l. I NMR (CDC13) : 2.76-2.94(m, 4H) , 3.927(s, 3H) , 3.943(s, 3H), 6.728(s, 1H) , 6.752(d, J=8.9Hz, 1H) , 7.12-7.26 (m, 4H) , 7.46-7.59(m, 1H), 8.04-8.10(m, 1H). MASS (M+Na)+445.1 (FR267958-N) i Example 341 (E0341) To a solution of E0336 (450mg) in dichloromethane (45ml) was added MCPBA (306mg) at room temperature. After stirring for 1 hour, the reaction mixture was washed with sat.NaHC03 (twice) andwater, dried over Na2S04, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel (50ml) to give 470mg of E0341 as an oil. (E0342) E0342 was prepared in a similar manner to that of E0341. white powder, mp. 92-93°C IR (KBr) : 3080, 2952, 1612, 1566, 1547, 1529, 1500cm-l Mass (ESI+) : 424 (M+H)+ 200MHz 1H NMR (DMS0-d6, d) : 1. 87-2 . 00 (2H, m) , 2.51 (3H, s) , 2.5 6-2.7 8(4H, m), 3.88(3H, s), 6.92(1H, d, J=8.9Hz), 7.19(1H, s), 7.21-7.3K4H, m) , 7.76(1H, dd, J=2.7, 8 . 9 Hz) , 8.19(1H, . o (E0343) To a solution of E0336 (450mg) in dichloromethane (45ml) was addedMCPBA (306mg) at room temperature. After stirring for 1 hour, the reaction mixture was washed with sat.NaHC03 (twice) andwater, dried over Na2S04, filtered and evaporated under reduced pressure. The residue was column chromatographed on silica gel (50ml) and recrystalized from EtOH to give 168mg (44%) of E0343. (E0344) 3-Chloroperoxybenzoic acid (407mg) was added to a solution of E0342 (666.3mg) in CH2C12 6ml under ice bath cooling. The reaction mixture was stirred at ambient temperature for lhour. The mixture was diluted with CHC13, washed with 1M NaOH, 5% aqueous sodium thiosulfate solution, and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was recrystallized from AcOEt-n-hexane to give E0344 (565 . 2mg) as a white powder. mp. 121-122°C IR (KBr) : 3120, 2954, 1707, 1693, 1647, 1612, 1566, 1547, 1529, 1500cm-l Mass (ESI + ) : 440 (M+H)+ 200MHz 1HNMR (DMSO-d6, d) : 1. 93-2 . 06 (2H, m) , 2.67-2.75 (2H, m) , 2.96(3H, s) , 3.04-3.13(2H, m) , 3.88(3H, s), 6.92 (1H, d, J=8.8 Hz), 7.19(1H, s) , 7 .19-7.31 (4H, m) , 7.76(1H, dd, J=8.8,2.8 Hz), 8.19(1H, d, J=2 . 8 Hz) (E0345) Oxalylchloride 28 6mg was added to a suspension of E0363 (0.43g) in CH2C12 3ml under ice bath cooling. DMF Idrop was added and the mixture was stirred at same temperature for lhour, and then concentrated in vacuo. To the residue, was added toluene and concentrated in vacuo. The residue was dissolved in THF 5ml and was added to a solution of aqueous ammoniumhydroxide solution 5ml with under ice bath cooling. The mixture was stirred at same temperature for lhour, diluted with AcOEt, washed successively with 1M HC1, saturated aqueous sodium bicarbonate solution, and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with AcOEt / n-hexane= 60%. The pure fraction was collected and concentrated in vacuo and the residue was crystallized from diisopropylether to give E0345 (287. 8mg) as a white powder. Mass (ESI + ) : 381 (M+H) + 200MHz 1H NMR (DMSO-d6, d) : 1.97(3H, s), 2.89(2H, t, J=6.8 Hz), 3.87(3H, s), 4.21(2H, t, J=6.8 Hz), 6.91(1H, d, J=8.8 Hz), 6.98(1H, s), 7.22(2H, d, J=8.4Hz), 7.28(2H, d, J=8.4 Hz), 7.38(1H, brs), 7.63-7.75(1H, brs), 7.72(1H, dd, J=2.7,8.8 Hz), 8.16(1H, d, J=2.7 Hz) (E0346) A mixture of E0109 (449.lmg) and sodium methoxide 238mg in formamide 5mi was heated at 70°C for 5hours. The mixture was allowed to cool to ambient temperature, and was partitioned between ethyl acetate and H20. The organic layer was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with CHC13, then MeOH / CHC13 = 2%, 5% to give E0346 (235.7mg) as a white powder. Mass (ESI+) : 338(M+H)+ 400MHz 1H NMR (DMSO-d6, d) : 2.70(2H, t, J=6.9 Hz), 3.56-3.62(2H, m), 3.79(3H, s) , 4.65(1H, t, J=5.1Hz), 6.92(1H, s) , 6.99(2H, d, J=8.9 Hz) , 7.15(2H, d, J=8. 3 Hz) , 7.20(2H, d, J=8.3Hz), 7.27(2H, d, J=8.9Hz), 7.33(1H, s), 7.64(1H, s) (E0347) E0347 was prepared in a similar manner to that of E0346. white powder Mass (ESI+) : 454 (M+H)+ 200MHz 1H NMR (DMSO-d6, d) : 3. 65-3.73 (2H, m) , 3.78 (3H, s) , 3.94-4.00(2H,m) , 4.8 6(1H, t, J=5.5Hz) , 6.88 (1H, s) , 6.91(2H, d, J=8.8 Hz) , 6.99(2H, d, J=8.9 Hz) f 7.16(2H, d, J=8.8 Hz) , 7.26(2H, d, J=8.9 Hz), 7.32(1H, s), 7.63(1H/ s) (E0348) E0348 was prepared in a similar manner to that of E0346. ABSTRACT A compound of the formula (I): wherein R1 is hydrogen or lower alkyl; R2 is lower alkyl, etc.; R3 is lower alkoxy, etc.; R4 is hydroxy, etc.; X is 0, S, etc.; Y is CH or N; Z is lower alkylene or lower alkenylene; anc m is 0 or 1; or salts thereof, which are useful as a medicament.

Documents:

1453-abs img.jpg

1453-chenp-2005 abstract-duplicate.pdf

1453-chenp-2005 claims-duplicate.pdf

1453-chenp-2005 description (complete)-duplicate 2.tif

1453-chenp-2005 description (complete)-duplicate 3.pdf

1453-chenp-2005 description (complete)-duplicate 4.pdf

1453-chenp-2005 description (complete)-duplicate 5.pdf

1453-chenp-2005 description (complete)-duplicate 6.pdf

1453-chenp-2005 description (complete)-duplicate 7.tif

1453-chenp-2005 description (complete)-duplicate.pdf

1453-chenp-2005-abstract.pdf

1453-chenp-2005-claims only.pdf

1453-chenp-2005-claims.pdf

1453-chenp-2005-correspondnece-others.pdf

1453-chenp-2005-correspondnece-po.pdf

1453-chenp-2005-description(complete).pdf

1453-chenp-2005-form 1.pdf

1453-chenp-2005-form 18.pdf

1453-chenp-2005-form 26.pdf

1453-chenp-2005-form 3.pdf

1453-chenp-2005-form 5.pdf

1453-chenp-2005-pct.pdf