Title of Invention

CARBAZOLE DERIVATIVE, SOLVATE AND ITS PHARMACEUTICALLY ACCEPTABLE SALT

Abstract

An object of the present invention is to provide novel carbazole derivatives, solvates thereof, or pharmaceutically acceptable salts thereof having an excellent adipose tissue weight reducing effect, hypoglycemic effect, and hypolipidemic effect, which are useful as a preventive and/or therapeutic agent for fatty liver, obesity, lipid metabolism abnormality, visceral adiposity, diabetes, hyperlipemia, impaired glucose tolerance, hypertension, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and the like. The above-mentioned object can be achieved by carbazole derivatives, solvates thereof, or pharmaceutically acceptable salts thereof, wherein the carbazole derivatives are represented by the following general formula (I): (In the formula (I), the ring A represents phenyl group or the like; X represents -O- or the like; Y represents =N- or the like; a and b represent methylene group or the like; both V and Z represent -O- or the like; W represents a C1-C10 alkylene group whose 1 or 2 hydrogen atoms may be substituted by a phenyl group or a C1-C6 alkyl group; 1,2-phenylene group; 1,3-cyclohexyl group; or the like; R1 represents methyl group or the like; R represents methoxy group or the like; and R represents carboxy group or the like.)

Full Text

Technical Field [0001] The present invention relates to carbazole derivatives, solvates thereof, or pharmaceutically acceptable salts thereof, as well as medical compositions and medicines containing such compounds. To be more specific, the present invention relates to novel carbazole derivatives, solvates thereof, pharmaceutically acceptable salts thereof, and the like having an excellent adipose tissue weight reducing effect, hypoglycemic effect, and hypolipidemic effect, which are useful as a preventive and/or therapeutic agent for fatty liver, obesity, lipid metabolism abnormality, visceral adiposity, diabetes, hyperlipemia, impaired glucose tolerance, hypertension, nonalcoholic fatty liver disease, non-alcoholic steatohepatitis, and the like. Background Art [0002] In recent years, lifestyle-related diseases such as obesity and diabetes are brought in question. Accordingly, transcription factors related to expression inductions of adipocyte differentiation marker genes are gaining attention. A peroxisome proliferator-activated receptor (hereinafter, also referred to as "PPAR") is known to be related to a lot of physiological and/or pathological phenomena such as fat metabolism, regulation of inflammation, cell differentiation, and functional regulation, thereby gaining special attention. [0003] The PPAR is a nuclear receptor belonging to a steroid/retinoid receptor superfamily of ligand responsive transcription factors (Curr. Opin. Chem. Biol., (1997), 1, 235-241; Cell, (1995), 83, 841-850). cDNAs of PPAR are cloned from various animal species and several isoform genes of PPAR are found. Among mammals, three subtypes, PPARa, PPARy, and PPAR8, are known (J. Steroid Biochem. Molec. Biol., (1994), 51, 157; Gene Expression, (1995), 4, 281; Biochem. Biophys. Res. Commun., (1996), 224, 431; Mol. Endocrinol., (1992), 6, 1634). [0004] The PPARy is known to be expressed mainly in the adipose tissue, immune organ, adrenal gland, spleen, small intestine, skeletal muscle, and liver. On the other hand, the PPARa is known to be expressed mainly in the liver, heart, kidney, adrenal gland, skeletal muscle, and retina. Also, the PPAR8 is known to be universally expressed without tissue specificity. Each of the PPARs forms a stable heterodimer with a retinoid X receptor (RXR), and bind with a specific DNA recognition sequence (PPRE) of the target gene for control. [0005] The PPARy is induced at a very early phase of an adipocyte differentiation and plays an important role in the adipocyte differentiation as a key regulating (controlling) factor. The first chemical identified as a direct ligand of PPAR was BRL49653, the thiazolidinediones (TZDs) having an antidiabetic effect on type II diabetes. Also, pioglitazone and ciglitazone that are antidiabetic drugs for type II diabetes and are TZD-type (Lehmann, J.M., J. (1995) Biol.Chem. 270, 12953-12956 (non-patent document 1), as well as 15-deoxy-A12,14-prostaglandin J2 that is a kind of prostaglandin metabolite (Cell, (1995), 83, 803-812; Cell, (1995), 83, 813-819 (non-patent document 2)) are known as candidates for intrinsic ligands of PPARy. Moreover, thiazolidinedione derivative that is an insulin sensitizer has been proved to increase the transcription activity of the PPARy, and known to have an insulin resistance improving effect, hypoglycemic effect, and antihyperlipidemic effect. [0006] Also, since adipocyte hypertrophy, fat accumulation and expression of insulin resistance are suppressed in a PPARy hetero deficient mouse, a model that the PPARy mediates adipocyte hypertrophy, fat accumulation and insulin resistance has been proposed (Mol. Cell, (1999), 4, 597 (non-patent document 3)), On the other hand, a thiazolidinedione (TZD) derivative that is a PPARy agonist is reported to have adipocyte differentiation inductive effect and to increase the number of adipose cells and the weight of adipose tissues (J. Clin. Invest., (1996), 98, 1004-1009 (non-patent document 4)). Therefore, while the TZD derivative is useful as a curative medicine for diabetes, possibility of promoting obesity is a concern. Also, while leptin is known as an antiobesity factor, the expression level of leptin is reported to decrease when the TZD derivative is administered (J. Biol. Chem., (1996), 271, 9455-9459 (non-patent document 5)). Based on these backgrounds, the PPARy antagonist is expected to control the differentiation of the adipose cell while simultaneously increasing the expression level of leptin, thereby acting as an antiobesity agent. [0007] Compounds that are PPARy receptor binder having the PPARy antagonist effect are disclosed by WO01/30343, WO02/060388, WO03/000685, WO2004/024705, and the like. These compounds are supposed to have an antiobesity effect, an adipose tissue weight reducing effect, a hypoglycemic effect, a hypolipidemic effect, and the like. [0008] On the other hand, WO01/26653, WO02/00255, WO02/00256, WO02/00257, and WO02/074342 (patent documents 1-5) disclose the following compound as a carbazole derivative. In these documents, the following compound is disclosed as a phospholipase A2 (sPLA2) inhibitor. Non-patent document 4: J. Clin. Invest., (1996), 98, 1004-1009 Non-patent document 5: J. Biol. Chem., (1996), 271, 9455-9459 Disclosure of the Invention [0019] An object of the present invention is to provide novel carbazole derivatives, solvate thereof, or pharmaceutically acceptable salt thereof having an excellent fatty tissue weight reducing effect, hypoglycemic effect, and blood lipid reducing effect, which are useful as a preventive and/or therapeutic agent for fatty liver, obesity, lipid metabolism abnormality, visceral adiposity, diabetes, hyperlipemia, impaired glucose tolerance, hypertension, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and the like. [0020] Another object of the present invention is to provide novel carbazole derivative, solvate thereof, or pharmaceutically acceptable salt thereof that is a PPAR modulator. Another of the present invention is to provide a novel carbazole derivative, solvate thereof, or pharmaceutically acceptable salt thereof showing a PPARy inhibitory effect or partial inhibitory effect (or partial agonistic effect). Another object of the present invention is to provide a novel carbazole derivative, solvate thereof, or pharmaceutically acceptable salt thereof showing a PPARy inhibitory effect or partial inhibitory effect (or partial agonistic effect) and showing a PPARa agonistic effect. [0021] Still another object of the present invention is to provide a preventive and/or therapeutic agent for metabolic syndrome and the like including a novel carbazole derivative, solvate thereof, or pharmaceutically acceptable salt thereof as an active ingredient. Yet another object of the present invention is to provide a medical composition or medicine including the above mentioned novel compounds. [0022] Further, yet another objectof the present invention is to provide a novel intermediate compound useful for the preparation of the above-mentioned novel compounds. [0023] In consideration of the above-mentioned circumstances, the present inventors have carried out careful studies and have consequently synthesized for the first time carbazole derivatives and salts thereof having the following structure. Moreover, the present inventors have found that these compounds control the PPAR and have preventive and/or therapeutic effect for disorders related to the PPAR, and have completed the present invention. [0024] [1] Namely, the present invention relates to a carbazole derivative, solvate thereof, or pharmaceutically acceptable salt thereof represented by the following general formula (I): [0025] [0026] In the formula (I), a ring A represents a C6-C10 aryl group which may have 1 to 3 substituent groups selected from a group A of substituent groups, or a 5- to 7-membered aromatic heterocyclic group which may have 1 to 3 substituent groups selected from the group A of substituent groups; X represents =N-, =CH-, -O, or -S-; Y represents =N-, -0-, or -S-; a and b may be same or different, and represent a C1-C4 alkylene group which may have a substituent group selected from the group A of substituent groups, a C2-C4 alkenylene group which may have a substituent group selected from the group A of substituent groups, or a C2-C4 alkynylene group which may have a substituent group selected from the group A of substituent groups; V and Z may be same or different, and represent a methylene group, =N-9 -NH-, - 0-, -S-, -S(=0)-, -S(=0)2-, -C(=0)-, -C(=0)NH-, or -NHC(=0)-; W represents a C1-C10 alkylene group which may have a substituent group selected from the group A of substituent groups, a C2-C10 alkenylene group which may have a substituent group selected from the group A of substituent groups, a C2-C10 alkynylene group which may have a substituent group selected from the group A of substituent groups, a C3-C7 cycloaliphatic hydrocarbon group which may have 1 to 3 substituent groups selected from the group A of substituent groups, or a C6-C10 arylene group which may have 1 to 3 substituent groups selected from the group A of substituent groups; R1 represents a hydrogen atom, a C1-C4 alkyl group which may have a substituent (V) which will be described later, and can be effectively used when specifically producing a carbazole derivative represented by the general formula (I) or the general formula (I!) according to the method B which will be described later. One whose T is -V-W-P1 in the general formula (1") is an intermediate represented by a formula (VIII) which will be described later, and can be effectively used when specifically producing a carbazole derivative represented by the general formula (I) or the general formula (I1) according to a method C which will be described later. [0045] [0046] In the formula (I"), a ring A represents a C6-C10 aryl group which may have 1 to 3 substituent groups selected from the group A of substituent groups, or a 5- to 7-membered aromatic heterocyclic group which may have 1 to 3 substituent groups selected from the group A of substituent groups; X represents =N-, =CH-, -0-, or -S-; Y represents =N-, -0-, or -S-; a and b may be same or different, and represent a C1-C4 alkylene group which may have a substituent group selected from the group A of substituent groups, a C2-C4 alkenylene group which may have a substituent group selected from the group A of substituent groups, or a C2-C4 alkynylene group which may have a substituent group selected from the group A of substituent groups; Z represents a methylene group, =N-, -NH-, -0-, -S-, -S(=0)-, -S(=0)2-, -C(=0)-, -C(=0)NH-, or -NHC(=0)s R1 represents a hydrogen atom, a C1-C4 alkyl group which may have a substituent group selected from the group A of substituent groups, a C2-C4 alkenyl group which may have a substituent group selected from the group A of substituent groups, a C2-C4 alkynyl group which may have a substituent group selected from the group A of substituent groups, or a Ci-C4 alkoxy group which may have a substituent group selected from the group A of substituent groups; R2 represents a hydrogen atom, a C1-C4 alkyl group which may have a substituent group selected from the group A of substituent groups, a C2-C4 alkenyl group which may have a substituent group selected from the group A of substituent groups, a C2-C4 Y represents =N-, -0-, or -S-; a and b may be same or different, and represent a C1-C4 alkylene group; Z represents a methylene group, -NH-, -0-, -S-, or -S(=0)-; R1 represents a C1-C4 alkyl group, or a C1-C4 alkoxy group; R represents a hydrogen atom, a C1-C4 alkoxy group, or a C1-C4 alkylthio group; T represents -OH, -OP, or -V-W-P; P represents an allyl group, a benzyl group, a methoxymethyl group, or a t-butyl group; V represents a methylene group, -NH-, -O-, -S-, or -S(=0)-; W represents {a C1-C10 alkylene group, a C2-C6 alkenylene group, or a C2-C6 alkynylene group} whose 1 or 2 hydrogens may be substituted by {halogen, a C1-C6 alkyl group, or a phenyl group}, or {a C3-C7 cycloalkylene group, a C3-C7 cycloalkenylene group, or a C6-C10 arylene group} whose 1 to 3 hydrogens may be substituted by {halogen, a C1-C6 alkyl group, or a phenyl group}; and P' represents a C1-C4 alkyl group, an allyl group, a benzyl group, or a methoxymethyl group. [0050] [23] A more preferable carbazole derivative, solvate thereof, or pharmaceutically acceptable salt thereof among those represented by the general formula (I") is the carbazole derivative, solvate thereof, or pharmaceutically acceptable salt thereof as described in the above-mentioned [19], wherein in the formula (I"): the ring A represents {a phenyl group, a 1-naphthyl group, or a 2-naphthyl group} whose 1 or 2 hydrogens may be substituted by {halogen, a C1-C4 alkyl group, or a C1-C4 alkoxy group}, or represents {a furyl group, a thienyl group, a pyrrolyl group, an imidazolyl group, an oxazolyl group, an isooxazoyl group, a thiazolyl group, an isothiazolyl group, a pyranyl group, or a pyridyl group} whose 1 or 2 hydrogens may be substituted by {halogen, a C1-C4 alkyl group, or a C1-C4 alkoxy group}; X and Y represent any one of: (i) X representing -O- and Y representing =N-, (ii) X representing =N- and Y representing -O- or -S-, and (iii) X representing -S- and Y representing =N-; a and b may be same or different, and represent a C1-C4 alkylene group; Z represents -NH-, -O-, -S-, or -S(-O)-; R1 represents a C1-C4 alkyl group, or a C1-C4 alkoxy group; R2 represents a hydrogen atom, a C1-C4 alkoxy group, or a C1-C4 alkylthio group; T represents -OH, -OP, or -V-W-P'; P represents an allyl group, a benzyl group, a methoxymethyl group, or a t-butyl group; V represents -NH-, -0-, -S-, or -S(=0)-; W represents {a C1-C10 alkylene group, a C2-C6 alkenylene group, or a C2-C6 [0055] In the formula (I), a ring A represents a C6-C10 aryl group which may have 1 to 3 substituent groups selected from a group A of substituent groups, or a 5- to 7-membered aromatic heterocyclic group which may have 1 to 3 substituent groups selected from the group A of substituent groups; X represents =N-, -CH-, -0-, or -S-; Y represents =N-, -O-, or -S-; a and b may be same or different, and represent a C1-C4 alkylene group which may have a substituent group selected from the group A of substituent groups, a C2-C4 alkenylene group which may have a substituent group selected from from the group A of substituent groups, or a C2-C4 alkynylene group which may have a substituent group selected from the group A of substituent groups; V and Z may be same or different, and represent a methylene group, =N-, -NH-, - O-, -S-, -S(=0)-, -S(-0)2-, -C(=0)-, -C(0)NH-, or -NHC(=0)-; W represents a C1-C10 alkylene group which may have a substituent group selected from the group A of substituent groups, a C2-C10 alkenylene group which may have a substituent group selected from the group A of substituent groups, a C2-CJO alkynylene group which may have a substituent group selected from the group A of substituent groups, a C3-C7 cycloaliphatic hydrocarbon group which may have 1 to 3 substituent groups selected from the group A of substituent groups, or a C6-C10 arylene group which may have 1 to 3 substituent groups selected from the group A of substituent groups; R1 represents a hydrogen atom, a C1-C4 alkyl group which may have a substituent group selected from the group A of substituent groups, a C2-C4 alkenyl group which may have a substituent group selected from the group A of substituent groups, a C2-C4 alkynyl group which may have a substituent group selected from the group A of substituent groups, or a C1-C4 alkoxy group which may have a substituent group selected from the group A of substituent groups; R represents, a hydrogen atom, a C1-C4 alkyl group which may have a substituent group selected from the group A of substituent groups, a C2-C4 alkenyl group may be substituted by halogen, a hydroxy group, a carboxy group, or a carbamoyl group. It is to be noted that the carbazole derivative represented by the formula (I) is preferably the carbazole derivative represented by the above-mentioned (F). [0056] In the present specification, the "Cm-Cn" implies that the carbon number is any number from m to n. [0057] The "aryl group" is a univalent group derived from an aromatic hydrocarbon by removal of one hydrogen atom bonded to the ring. As the C6-C10 aryl group, a phenyl group, an indenyl group, a 1-naphthyl group, and a 2-naphthyl group can be mentioned. [0058] The "aromatic heterocyclic group" is a heterocyclic group having within the ring 1 to 3 hetero atoms selected from a group including an oxygen atom, a nitrogen atom, and a sulfur atom. As the 5- to 7-membered aromatic heterocyclic group, a 5-membered aromatic heterocyclic group such as furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-oxadiazolyl, triazolyl, or thiadiazolyl; a 6-membered aromatic heterocyclic group such as pyranyl, pyridyl, pyridazinyl, pyrimidinyl, or pyrazinyl; or a 7-membered aromatic heterocyclic group such as azepinyl can be mentioned. As the aromatic heterocyclic group, the 5-membered aromatic heterocyclic group or the 6-membered aromatic heterocyclic group is preferable. [0059] The "alkylene group" is a bivalent group derived by removal of two hydrogen atoms from a straight-chain or branched-chain aliphatic hydrocarbon. As the C1-C100 alkylene group, a methylene group, a methylmethylene group, an ethylene group, a propylene group, a trimethylene group, a 1-methylethylene group, a tetramethylene group, a 1-methyltrimethylene group, a 2-methyltrimethylene group, a 3-methyltrimethylene group, a 1-methylpropylene group, a 1,1-dimethylethylene group, a pentamethylene group, a 1 -methyltetramethylene group, a 2-methyltetramethylene group, a 3-methyltetramethylene group, a 4-methyltetramethylene group, a 1,1-dimethyltrimethylene group, a 2,2-dimethyltrimethylene group, a 3,3-dimethyltrimethylene group, a hexamethylene group, a 1 -methylpentamethylene group, a 2-methylpentamethylene group, a 3-methylpentamethylene group, a 4-methylpentamethylene group, a 5-methylpentamethylene group, a 1,1-dimethyltetramethylene group, a 2,2-dimethyltetramethylene group, a 3,3-dimethyltetramethylene group, a 4,4-dimethyltetramethylene group, a heptamethylene group, a 1-methylhexamethylene group, a 2-methylhexamethylene group, a 5-methylhexamethylene group, a 3-ethylpentamethylene group, an octamethylene group, a 2-methylheptamethylene group, a 5-methylheptamethylene group, a 2-ethylhexamethylene group, a 2-ethyl-3-methylpentamethylene group, and a 3-ethyl-2- methylpentamethylene group can be mentioned. As the alkylene group, the C1-C4 alkylene group is preferable, and the C1-C2 alkylene group is more preferable. [0060] The "alkenylene group" is a bivalent group derived by removal of two hydrogen atoms from a straight-chain or branched-chain aliphatic hydrocarbon having a double bond. As the C2-C10 alkenylene group, an etenylene group, a 1-propenylene group, a 2-propenylene group, a 2-methyl-1 -propenylene group, a 1 -butenylene group, a 2-butenylene group, a 3-butenylene group, a 3-methyl-2-butenylene group, a 1-pentenylene group, a 2-pentenylene group, a 3-pentenylene group, a 4-pentenylene group, and a 1-hexenylene group can be mentioned. [0061] The "alkynylene group" is a bivalent group derived by removal of two hydrogen atoms from a straight-chain or branched-chain aliphatic hydrocarbon having a triple bond. As the C2-C10 alkynylene group, an ethynylene group, a 1-propynylene group, a 2-propynylene group, a 2-methyl-1-propynylene group, a 1-butynylene group, a 2-butynylene group, a 3-butynylene group, a 3-methyl-2-butynylene group, a 1-pentynylene group, a 2-pentynylene group, a 3-pentynylene group, a 4-pentynylene group, and a 1-hexynylene group can be mentioned. [0062] The "cycloaliphatic hydrocarbon group" means a saturated or unsaturated cycloaliphatic hydrocarbon group. As the C3-C7 cycloaliphatic hydrocarbon group, a cycloalkyl group such as a cyclopropyl group, a cyclobutyl group, cyclohexyl group, and cyclopentyl group; or a cycloalkenyl group such as a 2-cyclopentene-l-yl group, a 2-cyclohexene-1-yl group, and a 3-cyclohexene-l-yl group can be mentioned. [0063] The "arylene group" is a bivalent group derived from an aromatic hydrocarbon by removal of two hydrogen atoms bonded to the ring. As a ring composing a C6-C10 arylene group, a benzene ring or a naphthalene ring can be mentioned. [0064] The "alkyl group" is a univalent group derived by removal of one hydrogen atom from a straight-chain or branched-chain aliphatic hydrocarbon. As the C1-C6 alkyl group, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, a neopentyl group, a hexyl group, and an isohexyl group can be mentioned. As the C1-C4 alkyl group, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, and a tert-butyl group can be mentioned. [0065] The "alkenyl group" is a univalent group derived by removal of one hydrogen atom from a straight-chain or branched-chain aliphatic hydrocarbon having a double copper salt, nickel salt, and cobalt salt; inorganic salt such as ammonium salt; amine salt such as organic salt such as t-octylamine salt, dibenzylamine salt, morpholine salt, glucosamine salt, phenylglycinealkylester salt, ethylenediamine salt, N-methylglucamine salt, guanidine salt, diethylamine salt, triethylamine salt, dicyclohexylamine salt, N,N'-dibenzylethylenediamine salt, chloroprocaine salt, procaine salt, diethanolamine salt, N-benzyl-N-phenethylamine salt, piperazine salt, tetramethylammonium salt, and tris(hydroxymethyl)aminomethane salt; hydrohalic acid salt such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, and hydriodic acid; inorganic acid salt such as nitrate salt, perchlorate salt, sulfate salt, and phosphoric salt, or lower alkansulfonic acid salt such as methanesulfonic acid, trifluoromethanesulfonic acid, and ethanesulfonic acid; aryl sulfonic acid salt such as benzenesulfonic acid, p-toluenesulfonic acid, and the like; amino acid salt such as glutamic acid, and asparatic acid; organic acid of carboxylic acid salt such as fumaric acid, succinic acid, citric acid, tartaric acid, oxalic acid, and maleic acid; and amino acid salt such as ornithine acid salt, glutamate, and aspartate can be mentioned. Among these, the alkali metal salt is preferable, while the sodium salt is more preferable. [0093] In the compounds of the present invention, various isomers are included. For example, the carbazole derivative (I) of the above-mentioned general formula (I) includes an asymmetric carbon, and since there are cases where an asymmetric carbon is present on the substituent group, the optical isomer is included. For the compounds of the present invention, stereoisomers of an R configuration and S configuration exist. The compounds of the present invention include compounds including each of the stereoisomers or including the stereoisomers by arbitrary proportion. Such stereoisomers can be prepared by using optically-active ingredient to sythesize the compounds of the present invention or by optically resolving the prepared compounds of the present invention as desired by using a normal optical resolution method or separation method. More specifically, the optical resolution can be carried out by methods disclosed in the examples which will be described later. Moreover, geometric isomers such as cis forms and trans forms may be present in the compounds of the present invention. The compounds of the present invention include compounds including each of the geometric isomers or including the geometric isomers by arbitrary proportion. [0094] Moreover, the compounds of the present invention include compounds that are metabolized within an organism and converted into the compounds of the present invention, so-called prodrugs. [0095] (2. Method for preparation of the compounds of the present invention) The compounds of the present invention represented by the general formula (1) The compound represented by the general formula (II) can be prepared according to a publicly known production method such as one disclosed by WO01/38325, or a production method or the like which will be described later. Also, the compound represented by the general formula (III) can be prepared according to a publicly known production method such as one disclosed by DE2243574, or a production method or the like which will be described later. [0101] The inert solvents used for the process Al are not specifically limited as long as they are inactive against the above-mentioned reaction. As such inert solvents, ethers such as diethylether, tetrahydrofuran, and dioxane; halogenated hydrocarbons such as chloroform, and dichloromethane; aromatic hydrocarbons such as toluene, and xylene; amides such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidon; sulfoxides such as dimethylsulfoxide can be mentioned. These can be used singly or as a mixture of two or more kinds in appropriate proportions. Among these inert solvents, the amides such as the N,N-dimethylformamide are preferable. [0102] As the bases used for the process Al, alkali metal hydroxide such as sodium hydroxide, and potassium hydroxide; alkali metal salt such as sodium carbonate, potassium carbonate, and cesium carbonate; metal hydride such as sodium hydride, and potassium hydride; metal alkoxide such as sodium methoxide, sodium ethoxide, and potassium tert-butoxide; or organic alkali metal salt such as LDA, NaHMDS, KHMDS, LiHMDS can be mentioned. Specifically when E in the formula is a halogen atom, alkali metal hydroxide, metal hydride, or metal alkoxide is preferable among these bases. As the amount of the base, 1-5 mol equivalent weight for the compound (III) can be mentioned. [0103] While the reaction temperature in the process Al may be adjusted according to the ingredient, the solvent, the base, and the like in the process Al, it is usually -40 °C to 150 °C, and preferably -10 °C to 120 °C. The reaction temperature in the process Al may be 10°Cto50°C. [0104] While the reaction time in the process Al may be adjusted according to the ingredient, the solvent, the base, and the like in the process A1, it is usually 0.5 hour to 24 hours and preferably 0.5 hour to 2 hours. [0105] The compound (I) of the present invention is prepared from the reaction mixture after completing the process Al according to a method generally used in the field of the organic synthesis. For example, when the target compound is an insoluble precipitate, the target compound can be prepared by filtration of the reaction mixture, followd by washing with a solvent. Also, when the target compound is not an insoluble precipitate, the target compound can be prepared by using nonmiscible liquids such as organic solvent and water for separation, separating an organic layer including the target compound, followed by washing with water or the like and drying (extraction). [0106] The prepared target compound may be separated and/or purified as necessary. For such a separating and/or refining method, a method generally used in the field of organic synthesis may be adopted. As such a separating and/or refining method, a method can be mentioned where recrystallization, reprecipitation, chromatography, elution by the eluent, and the like are arbitrarily combined. [0107] It is to be noted that the compound (I) of the present invention may be extracted after changing the carboxyl group at the end into salt such as alkali metal. [0108] Also, in case the compound (I) of the present invention has optical isomers, they may be separated and/or synthesized by a publicly known method. For example, an optical active material may be prepared by using an optically-active intermediate. Also, at the final process of the synthesis or the like, the optical active material may be prepared by using an asymmetric reaction. Moreover, the optical active material may be prepared by performing an optical resolution to the mixture according to usual methods. It is to be noted that the above-mentioned optically-active intermediate can be prepared by utilizing chiral synthesis, asymmetric reaction, or optical resolution in the same way as menthioned above. [0109] (2.2. Method for preparation of the compounds of the present invention-Method B-) Hereinafter, an example of a method (method B) for preparation of the compounds of the present invention represented by the general formula (I) which is different from the above-mentioned method will be described. The method B includes the processes shown in the following process chart. general formula (V) from the compound represented by the general formula (II) and the carbazole derivative represented by the general formula (IV). The process Bl can be carried out according to a constantly carried out method in the field of organic synthesis and the like. The process Bl is generally carried out in an inert solvent. The process Bl may be carried out under the presence of a base. In such a case the compound (II) may be dissolved in an inert solvent, a base may be added under stirring or without stirring, and then the compound (IV) may be added under stirring or without stirring. [0114] The inert solvents used for the process Bl are not specifically limited as long as they are inactive against the above-mentioned reaction. As such inert solvents, alcohols such as methanol, ethanol, and isopropanol; ethers such as diethylether, tetrahydrofuran, and dioxane; halogenated hydrocarbons such as chloroform, and dichloromethane; aromatic hydrocarbons such as toluene, and xylene; amides such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; sulfoxides such as dimethylsulfoxide; or water can be mentioned. These inert solvents can be used singly or as a mixture of two or more kinds. Among these inert solvents, amides are preferable. [0115] As the bases used for the process Bl, alkali metal hydroxide such as sodium hydroxide, and potassium hydroxide; alkali metal salt such as sodium carbonate, potassium carbonate, and cesium carbonate; metal hydride such as sodium hydride, and potassium hydride; metal alkoxide such as sodium methoxide, sodium ethoxide, and potassium tert-butoxide; or organic alkali metal salt such as LDA, NaHMDS, KHMDS, and LiHMDS can be mentioned. Among these bases, alkali metal hydroxide or metal hydride is preferable. Specifically, when the E is a halogen atom, sodium hydroxide, potassium hydroxide, or sodium hydride is preferable among these bases. [0116] A preferable aspect of the process Bl is dissolving the compound (II) in the inert solvent while stirring the solution, followed by adding the base while stirring the solution, and further followed by adding the compound (IV). When dissolving the compound (II) in the inert solvent while stirring the solution, it is preferable to perform in a state where the solution is cooled in an ice bath. [0117] While the reaction temperature in the process Bl may be adjusted according to the ingredient, the solvent, the base, and the like in the process Bl, it is usually -40 °C to 150 °C, and preferably -10 °C to 120 °C. The reaction temperature in the process Bl may be -10 °C to 50 °C, and the reaction under ice-cooling may be carried out. [0118] While the reaction time in the process Bl may be adjusted according to the ingredient, the solvent, the base, and the like in the process Bl, it is usually 0.5 hour to 24 hours and preferably 0.5 hour to 2 hours. [0119] The target compound (V) is prepared from the reaction mixture after completing the process Bl according to a method generally used in the field of organic synthesis. For example, when the target compound is an insoluble precipitate, the target compound can be prepared by filtration of the reaction mixture, followed by washing with a solvent. Also, when the target compound is not an insoluble precipitate, the target compound can be prepared by using nonmiscible liquids such as organic solvent and water for separation, separating an organic layer including the target compound, followed by washing with water or the like and drying (extraction). [0120] The prepared target compound may be separated and/or purified as necessary. For such a separating and/or refining method, a method generally used in the field of organic synthesis may be adopted. As such a separating and/or refining method, a method can be mentioned where recrystallization, reprecipitation, chromatography, elution by the eluent, and the like are arbitrarily combined. [0121] (2.2.2. Process B2) The process B2 is a process (process of protecting group removal reaction) for preparation of the compound represented by the general formula (VI) from the compound represented by the general formula (V). The process B2 can be carried out according to a constantly carried out method in the field of organic synthesis and the like. The process B2 is generally carried out in an inert solvent. The process Bl may be carried out under the presence of a catalyst. Also, the process Bl may be carried out under the presence of acid. In such a case the compound (V) may be dissolved in an inert solvent, acid may be added under stirring or without stirring. It is to be noted that the process B2 is preferable to be carried out by performing a reflux while adding the acid to the solution. [0122] The inert solvents used for the process B2 are not specifically limited as long as they are inactive against the above-mentioned reaction. As such inert solvents, alcohols such as methanol, ethanol, and isopropanol; ethers such as diethylether, tetrahydrofuran, and dioxane; halogenated hydrocarbons such as chloroform, and dichloromethane; aromatic hydrocarbons such as toluene, and xylene; amides such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; sulfoxides such as dimethylsulfoxide; or water can be mentioned. These inert solvents can be used singly or as a mixture of two or more kinds. Among these inert solvents, ethers such as tetrahydrofuran or alcohols such as ethanol are preferable. As the catalysts used for the process B2, palladium acetate, triphenylphosphine, palladium-carbon, Raney nickel, platinum oxide, platinum black, rhodium-aluminum-oxide, triphenylphosphine-rhodium chloride, and palladium-barium sulfate can be mentioned. The preferable catalyst among these is palladium acetate or triphenylphosphine. [0124] As the acids used for the process B2, inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid, and phosphoric acid; Bronsted acid such as organic acid such as acetic acid, formic acid, oxalic acid, methanesulfonic acid, p-toluenesulfonic acid, camphorsulfonic acid, trifluoroacetic acid, and trifluoromethanesulfonic acid; Lewis acid such as zinc chloride, tin tetrachloride, boron trichloride, boron trifluoride, and boron tribromide; or acidic ion-exchange resin can be mentioned. These acids can be used singly or as a mixture of two or more kinds. The preferable acid among these acids is the organic acid such as the formic acid. [0125] While the reaction temperature in the process B2 may be adjusted according to the ingredient, the solvent, the base, and the like in the process B2, it is usually -40 °C to 150 °C, and preferably -10 °C to 120 °C. The reaction temperature in the process B2 may be 10°Cto50°C. [0126] While the reaction time in the process B2 may be adjusted according to the ingredient, the solvent, the base, and the like in the process B2, it is usually 0.5 hour to 24 hours and preferably 0.5 hour to 10 hours. [0127] The target compound (VI) is prepared from the reaction mixture after completing the process B2 according to a method generally used in the field of organic synthesis. For example, when the target compound is an insoluble precipitate, the target compound can be prepared by filtration of the reaction mixture, followed by washing with a solvent. Also, when the target compound is not an insoluble precipitate, the target compound can be prepared by using nonmiscible liquids such as organic solvent and water for separation, separating an organic layer including the target compound, followed by washing with water or the like and drying (extraction). [0128] The prepared target compound may be separated and/or purified as necessary. For such a separating and/or refining method, a method generally used in the field of organic synthesis may be adopted. As such a separating and/or refining method, a method can be mentioned where recrystallization, reprecipitation, chromatography, elution by the eluent, and the like are arbitrarily combined. (2.2.3. Process B3) The process B3 is a process for preparation of the compound represented by the general formula (I) by having a condensation reaction between the carbazole derivative represented by the general formula (VI) and the compound represented by the general formula (VII). The process B3 can be carried out according to a constantly carried out method in the field of organic synthesis and the like. The process B3 is generally carried out in an inert solvent. The process B3 may be carried out under the presence of a catalyst. Also, the process B3 may be carried out under the presence of a base. In such a case the compound (VI) may be dissolved in an inert solvent, a base may be added under stirring or without stirring, and then the compound (VII) may be added under stirring or without stirring. It is to be noted that when the W of the compound (VII) represents an aromatic hydrocarbon group, the reaction may be carried out under the presence of the catalyst according to the method reported in "Organic Letters, 2003, Volume 5, P3799". [0130] The inert solvents used for the process B3 are not specifically limited as long as they are inactive against the above-mentioned reaction. As such inert solvents, alcohols such as methanol, ethanol, and isopropanol; ethers such as diethylether, tetrahydrofuran, and dioxane; halogenated hydrocarbons such as chloroform, and dichloromethane; aromatic hydrocarbons such as toluene, and xylene; amides such as TM,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; sulfoxides such as dimethylsulfoxide; or water can be mentioned. Among these inert solvents, amides such as N,N-dimethylformamide or ethers such as dioxane are preferable. [0131] As the bases used for the process B3, alkali metal hydroxide such as sodium hydroxide, and potassium hydroxide; alkali metal salt such as sodium carbonate, potassium carbonate, and cesium carbonate; metal hydride such as sodium hydride, and potassium hydride; metal alkoxide such as sodium methoxide, sodium ethoxide, and potassium tert-butoxide; or organic alkali metal salt such as LDA, NaHMDS, KHMDS, and LiHMDS can be mentioned. These can be used singly or as a mixture of two or more kinds. Among these bases, metal hydride such as sodium hydride, or alkali metal salt such as potassium carbonate is preferable. As the amount of base in the process B3, 1-5 mol equivalent weight for the compound (VI) can be mentioned. [0132] As the catalysts used for the process B3, metal catalyst such as copper or palladium can be mentioned. Among these, copper catalyst is preferable, and copper iodide, copper bromide, copper chloride, copper dichloride, copper acetate, or copper sulfate can be specifically mentioned. It is to be noted that the process B3 may be carried out in the presence of amino acid such as N,N-dimethylaminoglycine. Use of the metal catalyst and the amino acid is a preferable aspect of the process B3. [0133] While the reaction temperature in the process B3 may be adjusted according to the ingredient, the solvent, the base, and the like in the process B3, it is usually -40 °C to 150 °C, and preferably -10 °C to 120 °C. The reaction temperature in the process B3 may be 50 °C to 100 °C. [0134] While the reaction time in the process B3 may be adjusted according to the ingredient, the solvent, the base, and the like in the process B3, it is usually 0.5 hour to 24 hours and preferably 0.5 hour to 2 hours. [0135] The target compound (V) is prepared from the reaction mixture after completing the process B3 according to a method generally used in the field of organic synthesis. For example, when the target compound is an insoluble precipitate, the target compound can be prepared by filtration of the reaction mixture, followed by washing with a solvent. Also, when the target compound is not an insoluble precipitate, the target compound can be prepared by using nonmiscible liquids such as organic solvent and water for separation, separating an organic layer including the target compound, followed by washing with water or the like and drying (extraction). [0136] The prepared target compound may be separated and/or purified as necessary. For such a separating and/or refining method, a method generally used in the field of organic synthesis may be adopted. As such a separating and/or refining method, a method can be mentioned where recrystallization, reprecipitation, chromatography, elution by the eluent, and the like are arbitrarily combined. [0137] (2.3. Method for preparation of the compounds of the present invention-Method C-) Hereinafter, an example of a method (method C) for preparation of the compounds of the present invention represented by the general formula (I) which is different from the above-mentioned method will be described. The method C is a method for preparation of the target compound by converting the substituent group such as a method for preparation of the target coupound represented by the general formula (I) by converting the substituent group after producing a compound represented by the general formula (I). The method C is effectively used when the R is a hydrogen atom. The method C includes the processes shown in the following process chart. [0139] In the above-mentioned formulas, A, V, W, X, Y, Z, b, R , R, and R respectively represent synonymous definition with those mentioned above. E represents a leaving group. As a specific example of E, a halogen atom can be mentioned, and a chlorine atom or a bromine atom can be mentioned more specifically. P! represents a protecting group. As a specific P', a methyl group, an ethyl group, a butyl group, an allyl group, a benzyl group, a methoxymethyl group, or a tert-butyl group can be mentioned. [0140] (2.3.1. Process CI) The process CI is a process for preparation of the compound represented by the general formula (VIII) from the compound represented by the general formula (II) and the carbazole derivative represented by the general formula (IV). The process CI can be carried out according to a constantly carried out method in the field of organic synthesis and the like. The process CI is generally carried out in an inert solvent. The process CI may be carried out under the presence of a base. In such a case the compound (II) may be dissolved in an inert solvent, a base may be added under stirring or without stirring, and then the compound (IV) may be added under stirring or without stirring. [0141] The inert solvents used for the process CI are not specifically limited as long as they are inactive against the above-mentioned reaction. As such inert solvents, alcohols such as methanol, ethanol, and isopropanolly ethers such as diethylether, tetrahydrofuran, and dioxane; halogenated hydrocarbons such as chloroform, and dichloromethane; aromatic hydrocarbons such as toluene, and xylene; amides such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; sulfoxides such as dimethylsulfoxide; or water can be mentioned. These inert solvents can be used singly or as a mixture of two or more kinds. Among these inert solvents, amides are preferable. [0142] As the bases used for the process CI, alkali metal hydroxide such as sodium hydroxide, and potassium hydroxide; alkali metal salt such as sodium carbonate, potassium carbonate, and cesium carbonate; metal hydride such as sodium hydride, and potassium hydride; metal alkoxide such as sodium methoxide, sodium ethoxide, and potassium tert-butoxide; or organic alkali metal salt such as LDA, NaHMDS, KHMDS, and LiHMDS can be mentioned. Among these bases, metal hydride is preferable. Specifically, when the E is a halogen atom, sodium hydride is preferable among these bases. [0143] A preferable aspect of the process CI is dissolving the compound (II) in the inert solvent while stirring the solution, followed by adding the base while stirring the solution, and further followed by adding the compound (IV). When dissolving the compound (II) in the inert solvent while stirring the solution, it is preferable to perform in a state where the solution is cooled in an ice bath. [0144] While the reaction temperature in the process CI may be adjusted according to the ingredient, the solvent, the base, and the like in the process CI, it is usually -40 °C to 150 °C, and preferably -10 °C to 120 °C. The reaction temperature in the process CI may be -10 °C to 50 °C, and the reaction under ice-cooling may be carried out. [0145] While the reaction time in the process CI may be adjusted according to the ingredient, the solvent, the base, and the like in the process CI, it is usually 0.5 hour to 24 hours and preferably 0.5 hour to 2 hours. [0146] The target compound (VIII) is prepared from the reaction mixture after completing the process CI according to a method generally used in the field of organic synthesis. For example, when the target compound is an insoluble precipitate, the target compound can be prepared by filtration of the reaction mixture, followed by washing with a solvent. Also, when the target compound is not an insoluble precipitate, the target compound can be prepared by using nonmiscible liquids such as organic solvent and water for separation, separating an organic layer including the target compound, followed by washing with water or the like and drying (extraction). The prepared target compound may be separated and/or purified as necessary. For such a separating and/or refining method, a method generally used in the field of organic synthesis may be adopted. As such a separating and/or refining method, a method can be mentioned where recrystallization, reprecipitation, chromatography, elution by the eluent, and the like are arbitrarily combined. [0148] (2.3.2. Process C2) The process C2 is a process for preparation of the carbazole derivative represented by the general formula (I) by deprotecting the compound represented by the general formula (VIII). Therefore, the method C is effectively used especially when the.3 is a hydrogen atom. However, the method C is not limited to such a case. The process C2 can be carried out according to a constantly carried out method in the field of organic synthesis and the like. The process C2 is generally carried out in an inert solvent. The process C2 may be carried out under the presence of a base. [0149] The inert solvents used for the process C2 are not specifically limited as long as they are inactive against the above-mentioned reaction. As such inert solvents, alcohols such as methanol, ethanol, and isopropanol; ethers such as diethylether, tetrahydrofuran, and dioxane; halogenated hydrocarbons such as chloroform, and dichloromethane; aromatic hydrocarbons such as toluene, and xylene; amides such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; sulfoxides such as dimethylsulfoxide; or water can be mentioned. These inert solvents can be used singly or as a mixture of two or more kinds. Among these inert solvents, ethers such as tetrahydrofuran or alcohols such as ethanol are preferable. [0150] As the catalysts used for the process C2, palladium acetate, triphenylphosphine, palladium-carbon, Raney nickel, platinum oxide, platinum black, rhodium-aluminum-oxide, triphenylphosphine-rhodium chloride, and palladium-barium sulfate can be mentioned. The preferable catalyst among these is palladium acetate or triphenylphosphine. [0151] As the bases used for the process C2, alkali metal hydroxide such as sodium hydroxide, and potassium hydroxide; alkali metal salt such as sodium carbonate, potassium carbonate, and cesium carbonate; metal hydride such as sodium hydride, and potassium hydride; metal alkoxide such as sodium methoxide, sodium ethoxide, and potassium tert-butoxide; or organic alkali metal salt such as LDA, NaHMDS, KHMDS, and LiHMDS can be mentioned. These can be used singly or as a mixture of two or more kinds. Among these bases, metal hydride such as sodium hydride, or alkali metal salt such as potassium carbonate is preferable. As the amount of the base in the process C2, 1-5 mol equivalent weight for the compound (VI) can be mentioned. [0152] While the reaction temperature in the process C2 may be adjusted according to the ingredient, the solvent, the base, and the like in the process C2, it is usually -40 °C to 150 °C, and preferably -10 °C to 120 °C. The reaction temperature in the process C2 may be 10°Cto50°C. [0153] While the reaction time in the process C2 may be adjusted according to the ingredient, the solvent, the base, and the like in the process C2, it is usually 0.5 hour to 24 hours and preferably 0.5 hour to 10 hours. [0154] The target compound (V) is prepared from the reaction mixture after completing the process C2 according to a method generally used in the field of the organic synthesis. For example, when the target compound is an insoluble precipitate, the target compound can be prepared by filtration of the reaction mixture, followed by washing with a solvent. Also, when the target compound is not an insoluble precipitate, the target compound can be prepared by using nonmiscible liquids such as organic solvent and water for separation, separating an organic layer including the target compound, followed by washing with water or the like and drying (extraction). [0155] The prepared target compound may be separated and/or purified as necessary. For such a separating and/or refining method, a method generally used in the field of organic synthesis may be adopted.As such a separating and/or refining method, a method can be mentioned where recrystallization, reprecipitation, chromatography, elution by the eluent, and the like are arbitrarily combined. [0156] (2.4. Method for preparation of the compounds of the present invention-Method D-) Hereinafter, an example of a method (method D) for preparation of the compounds of the present invention represented by the general formula (I) which is different from the above-mentioned method will be described. The method D is a method for preparation of the compounds represented by the general formula (I), followed by preparation of the salt thereof. According to this method, after the compound represented by the general formula (I) is dissolved in the inert solvent, the salt can be prepared by making alkali metal hydroxide such as sodium hydroxide and potassium hydroxide or organic acid salt such assodium 2-ethyl hexanoate react therewith. As the inert solvents in the method D, alcohol such as ethanol and 2-propanol, ester such as ethyl acetate and isobutyl acetate, or ketone such as acetone and methyl isobutyl ketone can be mentioned. As the concentration of the hydroxide used, 0.1 N to 10 N can be mentioned, while it may be 0.5 N to 5 N. The hydroxide, or the organic acid salt used is added to the compound (I), for example, by 1 equivalent weight to 10 equivalent weight. The reaction temperature in the method D is usually -40 °C to 150 °C, and preferably -10 °C to 120 °C. The reaction time in the method D is usually 0.1 hour to 24 hours and preferably 0.5 hour to 2 hours. [0157] (2.5. Method for preparation of the compound (II)) The compound represented by the general formula (II) can be prepared according to the method described, for example, in WO01/38325 and the method shown below (method E). [0158] [0159] In the above-mentioned formulas, A, W, X, Y, Z, b, R1, R, and R3 respectively represent synonymous definition with those mentioned above. As an example of E or E', a hydroxyl group, a halogen atom, or -OSO2R7 (R7 is a methyl group, a trifluoromethyl group, a phenyl group, a tolyl group, or a nitrophenyl group) can be mentioned. As a more specific E or E', a chlorine atom or a bromine atom can be mentioned. [0160] (2.5.1. Process El) The process El is a process for preparation of a compound represented by the general formula (X) by halogenating an end group a of the compound represented by the general formula (IX). The process El can be carried out according to a constantly carried out method in the field of organic synthesis and the like. The process El is generally carried out in an inert solvent. In the process El, the compound represented by the general formula (X) can be prepared by dissolving the compound represented by the general formula (IX) in solvent such as methylene chloride or chloroform, and adding chloride such as NaCIO, SOCl2 (thionyl chloride), PC13, or POCl3 (phosphorous oxychloride) dropwise into the solution. As the solvent, chloroform can be mentioned, and as a chloride added dropwise, phosphorous oxychloride can be mentioned. [0161] The compound (IX) can be prepared by purchasing commercialized products. Among the compounds (IX), specifically when the five-membered ring is an oxazole ring, it is preferable to prepare the compound (IX') by the following El* process. [0162] [0163] The El' process is a process for the preparation of the compound (IX') whose five-membered ring is an oxazole ring from the compound (XIII) and the compound (XIV). The El' process can be carried out by dissolving the compound (XIII) and compound (XIV) in acids, blowing in hydrochloride gas to be saturated, and further stirring. By the El1 process, the compound (IX') can be prepared not only when the A ring is a benzene ring or a naphthyl ring, but also when it is, for example, various aromatic hydrocarbon rings or aromatic heterocycles such as a furan ring, a thiophen ring, and a pyridine ring. [0164] As the acids used for the El' process, inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, perchloric acid, and phosphoric acid; Bronsted acid such as organic acid such as acetic acid, formic acid, oxalic acid, methanesulfonic acid, p-toluenesulfonic acid, camphorsulfonic acid, trifluoro acetic acid, and trifluoro methanesulfonic acid; Lewis acid such as zinc chloride, tin tetrachloride, boron trichloride, boron trifluoride, and boron tribromide; or acidic ion-exchange resin can be mentioned. These acids can be used singly or as a mixture of two or more kinds. The preferable acid among these acids is the organic acid such as the acetic acid. While the reaction temperature in the EV process may be adjusted according to the ingredient, the solvent, the base, and the like in the El' process, it is usually -40 °C to 150 °C, and preferably -10 °C to 10 °C. For example, the temperature at the time of blowing in the hydrochloride gas may be e.g. -10 °C to 20 °C, and the temperature at the time of stirring may be 20 °C to 40 °C. While the reaction time in the El' process may be adjusted according to the ingredient, the solvent, the base, and the like in the El' process, it is usually 0.5 hour to 24 hours and preferably 0.5 hour to 10 hours. [0166] (2.5.2. Process E2) The process E2 is a process for preparation of the compound represented by the general formula (XII) from the compound represented by the general formula (X) and the carbazole derivative represented by the general formula (XI). The process E2 can be carried out according to a constantly carried out method in the field of organic synthesis and the like. The process E2 is generally carried out in an inert solvent. The process E2 may be carried out under the presence of a base. In such a case the compound (II) may be dissolved in an inert solvent, a base may be added under stirring or without stirring, and then the compound (IV) may be added under stirring or without stirring. [0167] The inert solvents used for the process E2 are not specifically limited as long as they are inactive against the above-mentioned reaction. As such inert solvents, alcohols such as methanol, ethanol, and isopropanol; ethers such as diethylether, tetrahydrofuran, and dioxane; halogenated hydrocarbons such as chloroform, and dichloromethane; aromatic hydrocarbons such as toluene, and xylene; amides such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; sulfoxides such as dimethylsulfoxide; or water can be mentioned. Among these inert solvents, amides such as N,N-dimethylformamide or ethers such as dioxane are preferable. [0168] As the bases used for the process E2, alkali metal hydroxide such as sodium hydroxide, and potassium hydroxide; alkali metal salt such as sodium carbonate, potassium carbonate, and cesium carbonate; metal hydride such as sodium hydride, and potassium hydride; metal alkoxide such as sodium methoxide, sodium ethoxide, and potassium tert-butoxide; or organic alkali metal salt such as LDA, NaHMDS, KHMDS, and LiHMDS can be mentioned. These bases can be used singly or as a mixture of two or more kinds. Among these bases, alkali metal such as sodium hydroxide, and potassium hydroxide, metal hydride such as sodium hydride, or alkali metal salt such as potassium carbonate is preferable. As the amount of base in the process E2, 1-5 mol equivalent weight for the compound (X) can be mentioned. While the reaction temperature in the process E2 may be adjusted according to the ingredient, the solvent, the base, and the like in the process E2, it is usually -40 °C to 150 °C, and preferably -10 °C to 120 °C. The reaction temperature in the process E2 may be 10°Cto50°C. [0170] While the reaction time in the process E2 may be adjusted according to the ingredient, the solvent, the base, and the like in the process E2, it is usually 0.5 hour to 24 hours and preferably 0.5 hour to 10 hours. [0171] (2.5.3. Process E3) The process E3 is a process (process of halogenating hydroxyl group) for preparation of the compound represented by the general formula (II) from the compound represented by the general formula (XII). The process E3 can be carried out according to a constantly carried out method in the field of organic synthesis and the like. In the process E3, the compound represented by the general formula (X) can be prepared by dissolving the compound represented by the general formula (IX) in solvent such as methylene chloride or chloroform, and adding chloride such as NaCIO, SOCh (thionyl chloride), PC13, or POCI3 (phosphorous oxychloride) dropwise into the solution. As the solvent, methylene chloride can be mentioned, and as a chloride added dropwise, thionyl chloride can be mentioned. [0172] (2.6. Method for preparation of the compound (III) and compound (IV)) The compound represented by the general formula (III), and the compound represented by the general formula (IV) or general formula (IV) can be prepared according to the method described, for example, in DE2243574 and the method shown below (method F). [0173] [0174] In the above-mentioned formula, V, W, and R3 respectively represent synonymous definition with those mentioned above. As an example of E, a hydroxyl group, a halogen atom, or -OS02R7 (R7 is a methyl group, a trifluoromethyl group, a phenyl group, a tolyl group, or a nitrophenyl group) can be mentioned. As a more specific E, a chlorine atom or a bromine atom can be mentioned. [0175] (2.6.1. Process Fl) The process Fl is a process for preparation of the compound represented by the general formula (III) from the compound represented by the general formula (XV) and the carbazole derivative represented by the general formula (VII). The process Fl can be carried out according to a constantly carried out method in the field of organic synthesis and the like. The process Fl is generally carried out in an inert solvent. The process Fl may be carried out under the presence of a base. In such a case the compound (XV) may be dissolved in an inert solvent, a base may be added under stirring or without stirring, and then the compound (VII) may be added under stirring or without stirring. [0176] The inert solvents used for the process Fl are not specifically limited as long as they are inactive against the above-mentioned reaction. As such inert solvents, alcohols such as methanol, ethanol, and isopropanol; ethers such as diethylether, tetrahydrofuran, and dioxane; halogenated hydrocarbons such as chloroform, and dichloromethane; aromatic hydrocarbons such as toluene, and xylene; amides such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; sulfoxides such as dimethylsulfoxide; or water can be mentioned. These inert solvents can be used singly or as a mixture of two or more kinds. Among these inert solvents, amides are preferable. [0177] As the bases used for the process Fl, alkali metal hydroxide such as sodium hydroxide, and potassium hydroxide; alkali metal salt such as sodium carbonate, potassium carbonate, and cesium carbonate; metal hydride such as sodium hydride, and potassium hydride; metal alkoxide such as sodium methoxide, sodium ethoxide, and potassium tert-butoxide; or organic alkali metal salt such as LDA, NaHMDS, KHMDS, and LiHMDS can be mentioned. These bases can be used singly or as a mixture of two or more kinds. Among these bases, alkali metal hydroxide such as sodium hydroxide and potassium hydroxide, metal hydride such as sodium hydride, or alkali metal salt such as potassium carbonate is preferable. As the amount of the base in the process Fl, 1-5 mol equivalent weight for the compound (XV) can be mentioned. [0178] While the reaction temperature in the process Fl may be adjusted according to the ingredient, the solvent, the base, and the like in the process Fl, it is usually -40 °C to 150 °C, and preferably -10 °C to 120 °C. The reaction temperature in the process Fl may be 50 °C to 100 °C. [0179] While the reaction time in the process Fl may be adjusted according to the ingredient, the solvent, the base, and the like in the process Fl, it is usually 0.5 hour to 24 hours and preferably 3 hour to 10 hours. [0180] (3. Medicines and the like) The compounds of the present invention are new substances for which various applications are expected. Moreover, the compounds of the present invention, as exemplified by the examples which will be described later, have excellent PPARy inhibitory effect or PPARy partial inhibitory effect, as well as PPARa agonistic effect, function as antagonists or partial antagonists of the PPARy, and also function as agonists of the PPARa. The compounds of the present invention have an excellent adipose tissue weight reducing effect, hypoglycemic effect and hypolipidemic effect. Also, the compounds of the present invention are effective in suppression of body weight increase, improvement of insulin resistance, suppression of glucose tolerance reduction, suppression of insulin sensitivity reduction, and the like. Therefore, the compounds of the present invention are useful as preventive agents or therapeutic agents for fatty liver, obesity, lipid metabolism abnormality, visceral adiposity, diabetes, hyperlipemia, impaired glucose tolerance, hypertension, non-alcoholic fatty liver disease, nonalcoholic steatohepatitis, and the like. The compounds of the present invention are useful as preventive agents or therapeutic agents expecially for disorders involving the PPAR such as fatty liver. The compounds of the present invention that function as the antagonist or partial antagonist of the PPARy are useful as preventive agents or therapeutic agents especially for fatty liver, obesity, lipid metabolism abnormality, visceral adiposity, diabetes, or impaired glucose tolerance. Also, the compounds of the present invention that function as agonists of the PPARa are useful as preventive agents or therapeutic agents especially for hyperlipemia or hypertension. [0181] The compounds of the present invention are useful as preventive agents or therapeutic agents for a series of clinical conditions based on insulin resistance, namely the metabolic syndrome. The "metabolic syndrome" represents a state where a series of clinical conditions such as type II diabetes based on insulin resistance, hyperlipemia, visceral obesity, fatty liver, and the like coexist, and is also called a syndrome X, insulin resistant syndrome, visceral obesity syndrome, or multiple risk factor syndrome. It is known that partial agonists and partial antagonists in addition to agonists and antagonists are generally present in the nuclear receptor group. These are collectively called "modulators". The compounds of the present invention, as exemplified by the examples which will be described later, function as antagonists or partial antagonists of the PPARy, and also function as agonists of the PPARa, so that the present invention can also provide PPAR modulators, especially PPARy modulators or PPARa modulators. Having the above-mentioned effects, the compounds of the present invention can be used in prevention or therapy of fatty liver, obesity, lipid metabolism abnormality, visceral adiposity, diabetes, hyperlipemia, impaired glucose tolerance, hypertension, non-alcoholic fatty liver disease, or non-alcoholic steatohepatitis. Moreover, the compounds of the present invention can be used for the preparation of preventive agents or therapeutic agents for fatty liver, obesity, lipid metabolism abnormality, visceral adiposity, diabetes, hyperlipemia, impaired glucose tolerance, hypertension, nonalcoholic fatty liver disease, or non-alcoholic steatohepatitis. [0182] Moreover, medical compositions (hereinafter, occasionally referred to as "medical compositions of the present invention") including the compounds of the present invention and a pharmaceutically acceptable carrier or the like are useful as preventive agents or therapeutic agents for fatty liver, obesity, lipid metabolism abnormality, visceral adiposity, diabetes, hyperlipemia, impaired glucose tolerance, hypertension, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and the like. Namely, by the present specification, usage of the compounds of the present invention for preparation of medical compositions can be provided, and to describe more specifically, usage of the medical compositions for prevention and therapy of fatty liver, obesity, lipid metabolism abnormality, visceral adiposity, diabetes, hyperlipemia, impaired glucose tolerance, hypertension, non-alcoholic fatty liver disease, or nonalcoholic steatohepatitis can be provided. Also, by the present specification, usage of the compounds of the present invention for preventing or treating fatty liver, obesity, lipid metabolism abnormality, visceral adiposity, diabetes, hyperlipemia, impaired glucose tolerance, hypertension, non-alcoholic fatty liver disease, or non-alcoholic steatohepatitis can be provided. [0183] When the compounds of the present invention are used as the above-mentioned preventive agents or therapeutic agents, the compounds may be administered per se, or mixed with a pharmaceutically acceptable carrier or the like to be administered. Such preventive agents or therapeutic agents can be prepared by publicly known methods. As agents using the compounds of the present invention, oral agents such as tablets, capsules, granules, powder medicines, and syrups; and parenteral agents such as injectable solutions and suppositories can be mentioned. These agents can be administered orally or parenterally. [0184] As a pharmaceutically acceptable carrier, one arbitrarily selected from vehicle, diluent, alubricant, binder, disintegrant, stabilizer, and flavoring agent can be mentioned. [0185] As the vehicle, for example, organic vehicle such as sugar derivative such as lactose, sucrose, glucose, mannitol, and sorbitol; starch derivative such as cornstarch, potato starch, alpha-starch, and dextrin; cellulose derivative such as crystalline cellulose; gum arabic; dextran; and organic vehicle such as pullulan: as well as inorganic vehicle such as silicate derivative such as light anhydrous silicic acid, synthetic aluminum silicate, calcium silicate, and magnesium aluminometasilicate; phosphoric acid salt such as calcium hydrogen phosphate; carbonate such as calcium carbonate; and sulfate salt such as calcium sulfate can be mentioned. [0186] As the lubricant, for example, stearate metal salt such as stearate, calcium stearate, and magnesium stearate; talc; colloid silica; waxes such as magnesium aluminum silicate, and whale wax; boracic acid; adipic acid; sulfate salt such as sodium sulfate; glycol; fumaric acid; sodium benzoate; DL leucine; fatty acid sodium salt; lauryl sulfate salt such as sodium lauryl sulfate, and sodium lauryl sulfate magnesium; silicates such as silicic anhydride, and silicate hydrate; and the above-mentioned starch derivative can be mentioned. [0187] As the binder, for example, hydroxypropylcellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, macrogol, and compounds same as those of the above-mentioned vehicle can be mentioned. [0188] As the disintegrant, for example, cellulose derivative such as hydroxypropylcellulose of low substitution degree, carboxymethylcellulose, carboxymethylcellulose calcium, and internally bridged carboxymethylcellulose sodium; chemically-modified starches and celluloses such as carboxymethylstarch, sodium starch glycolate, and bridged polyvinylpyrrolidone can be mentioned. [0189] As the stabilizer, for example, p-hydroxybenzoic esters such as methylparaben, and propylparaben; alcohols such as chlorobutanol, benzyl alcohol, and phenylethyl alcohol; benzalkonium chloride; phenols such as phenol, and cresol; thimerosal; dehydroacetic acid; and sorbic acid can be mentioned. As the flavoring agent, for example, sweetener, acidulant, aroma chemical, and the like can be mentioned. As the diluent, sterile water, sterile organic solvent, aqueous starch, or the like can be mentioned. [0190] The agents of the present invention can be prepared by using the compounds of the present invention or the medical compositions of the present invention according to methods that are publicly known. Tablets can be prepared, for example, by tableting the medical composition in which the compounds of the present invention and a publicly known carrier are mixed with a tableting machine. Capsules and suppositories can be prepared, for example, by enclosing the compounds of the present invention or the medical compositions of the present invention in carriers shaped as capsules and the like. Syrups can be prepared, for example, by dissolving the compounds of the present invention or the medical compositions of the present invention in liquid solvent such as syrup. Powder medicines such as granules can be prepared by powderizing the compounds of the present invention or the medical compositions of the present invention by publicly known means. [0191] Dosage of the compounds of the present invention may be appropriately adjusted according to symptom, age, gender, administration method, and the like. For example, in case of oral administration, lower limit of 0.001 mg/kg weight (preferably 0.01 mg/kg weight) and upper limit of 500 mg/kg weight (preferably 50 mg/kg weight) may be administered at a time. Also, in case of intravenous administration, lower limit of 0.005 mg/kg weight (preferably 0.05 mg/kg weight) and upper limit of 50 mg/kg weight (preferably 5 mg/kg weight) may be administered at a time. As for number of doses, for example, one dose to several doses per day may be administered according to symptoms. [0192] Pharmacologic effects such as the PPARy inhibitory activity of the compounds of the present invention can be measured by using the pharmacologic testing method as described in the examples of tests that will be described later or methods pursuant thereto. [0193] While the present invention will be described below in more detail by using examples, the present invention is not limited to those examples. [0194] Reference 1 Preparation of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2- phenyloxazole [0195] [0198] 500g of benzaldehyde and 476g of diacetylmonoxime were suspended in 1L of acetic acid and cooled in an ice bath. At internal temperature of 7 °C, hydrochloride gas is slowly blown in to be saturated. At room temperature, the mixture was stirred overnight. The reaction mixture was poured into 1.5kg of ice, and neutralized with 25. sodium hydroxide solution. The crystalline precipitate was isolated by filtration and washed with 1L of water and 1L of diisopropylether. The obtained crystals were dissolved in 3L of chloroform and insoluble matter was filtered off. The filtrate was dried with 200g of anhydrous sodium sulfate, filtered, and the filtrate was concentrated in vacuo. 3L of IPE was added to the residue to be crystallized, the crystal was isolated by filtration, dried under reduced pressure at 50 °C for 1 hour, and 440g of the subject compound was prepared. IH-NMR(400MHz, CDC13)5 ppm: 2.22(3H, d) 2.36(3H, d) 7.41-7.52(3H, m) 8.44-8.49(2H, m) [0199] Reference 1(b) Preparation of 4-(chloromethyl)-5-methyl-2-phenyloxazole [0201] 383g of phosphorous oxychloride was slowly added dropwise into chloroform (2L) solution of 430g of 4,5-dimethyl-2-phenyloxazole N-oxide. After the dropwise addition, the solution was stirred for 2 hours at room temperature. The reaction mixture was concentrated in vacuo, and 2L of ethyl acetate was added to the residue. The foregoing ethyl acetate solution was added to mixed solution of 2L of ice water and 1.2L of 25% sodium hydroxide solution under stirring. The liquid was separated, and the ethyl acetate layer was washed with 1L of brine, and dried with 300g of anhydrous sodium sulfate. After filtration in vacuo, the filtrate was concentrated. Ethanol:n-hexane=l:10 (1.1 L) was added to the crystalline residue, and then filtered off. The crystal was dried under reduced pressure at 40 °C for 1 hour, 32 lg of the subject compound was prepared. 1H-NMR(400MHz, CDC13)5 ppm: 2.43(3H, s) 4.56(2H, s) 7.42-7.46(3H, m) 7.98-8.02(2H, m) [0202] Reference 1(c) Preparation of (4-(5-methyl-2-phenyloxazole-4-yl)methoxy)-3-methoxyphenyl)methanol [0203] 31 lg of 4-(chloromethyl)-5-methyl-2-phenyloxazole, 277g of vanillyl alcohol, and 415g of powdered potassium carbonate were added to 1L of N,N-dimethylformamide and stirred at 90 °C for 1 hour. The reaction mixture was cooled to room temperature, and 2.5L of ice water was added to the reaction mixture under stirring. The precipitate crystal was filtered off, and washed with 1L of water and 0.5L of IPE. The obtained crystal was dissolved by heating into 2L of isopropyl alcohol. A part of the insoluble matter was filtered and the filtrate was stirred overnight. The precipitate crystal was isolated by filtration and washed with 0.5L of isopropyl alcohol. The obtained crystal was dried under reduced pressure and 325g of the subject compound was prepared. ]H-NMR(400MHz, CDC13)5 ppm: 1.77(1H, d) 2.41(3H, s) 3.88(3H, s) 4.63(2H, d) 5.05(2H, s) 6.87(1H, dd) 6.95(1H, d) 7.02(1H, d) 7.40-7.47(3H, m) 7.98-8.03(2H, m) [0205] Reference 1(d) Preparation of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2- phenyloxazole [0206] [0207] 315g of (4-(5-methyl-2-phenyloxazole-4-yl)methoxy)-3-methoxyphenyl) methanol was suspended in 1.5L of methylene chloride, and thionyl chloride was added thereto dropwise while being coolded in an ice bath. After the dropwise addition thereto, the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into mixture of 1.8L of 2 N sodium hydroxide solution and 1.8Kg of ice, stirred for 15 minutes, and separated. The organic layer was washed with 1L of brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo. Ethanol:hexane=l:10(1.65L) was added to the cryltalline residue and isolated by filtration. The crystal was dried under reduced pressure and 307g of the subject compound was prepared. 'H-NMRlyOOMHz, DMSO-d6)5 ppm: 2.44(3H, s) 3.76(3H, s) 4.72(2H, d) 4.99(2H, s) 6.99(1H, dd) 7.07(1H, d) 7.11(1H, d) 7.48-7.57(3H, m) 7.91-7.98(2H, m) [0208] Reference 2 Preparation of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-2-(furan-2-yl)-5- methyloxazole [0209] [0210] The subject compound was prepared by performing the same operation as those of the references 1(a) to 1(d) by using furfural instead of benzaldehyde in the reference 1(a). 'H-NMR(400MHz, DMSO-d6)8 ppm: 2.41(3H, s) 3.76(3H, s) 4.72(2H, d) 4.97(2H, s) 6.71(1H, dd) 6.98(1H, dd) 6.71(1H, dd) 6.98(1H, dd) 7.06(1H, d) 7.08(1H, d) 7.11(1H, uu; /.lyilyin, uuj [0211] Reference 3 Preparation of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-2-(thiophene-2-yl)-5- methyloxazole [0212] [0213] The subject compound was prepared by performing the same operation as those of the references 1(a) to 1(d) by using 2-thiophenealdehyde instead of benzaldehyde in the reference 1(a). 'H-NMR(400MHz, DMSO-d6)8 ppm: 2.41(3H, s) 3.76(3H, s) 4.72(2H, d) 4.95(2H, s) 6.98(1H, dd) 7.07(1H, m) 7.08(1H, dd) 7.21(1H, dd) 7.66(1H, dd) 7.77(1 H, dd) [0214] Reference 4 Preparation of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-2-(pyridine-4-yI)-5 methyloxazole [0215] The subject compound was prepared by performing the same operation as those of the references 1 (a) to 1 (d) by using 4-pyridinecarboxaldehyde instead of benzaldehyde in the reference 1(a). 1H-NMR(400MHz, CDC13)5 ppm: 2.45(3H, s) 3.89(3H, s) 4.57(2H, d) 5.07(2H, s) 6.92(1H, dd) 6.94(1H, d)7.01(lH, d) 7.85(2H, dd) 8.72(2H, dd) [0217] Reference 5 Preparation of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2- phenylthiazole [0218] [0219] The subject compound was prepared by performing the same operation as those of the references 1(c) to 1(d) by using 4-(chloromethyl)-5-methyl-2-phenylthiazole prepared by the method described in Tetrahedron Letters (2004, Volume 45, P69) instead of 4-(chloromethyl)-5-methyI-2-phenyloxazole in the reference 1(c). 1H-NMR(400MHz, DMSO-d6)5 ppm: 2.50(3H, s) 3.76(3H, s) 4.72(2H, d) 5.13(2H, s) 6.99(1 H, dd) 7.06(1H, d) 7.14(1 H, d) 7.45-7.52(3H, m) 7.85-7.91(2H, m) [0220] Reference 6 Preparation of 5-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-4-methyl-2- phenylthiazole [0221] [0222] The subject compound was prepared by performing the same operation as those of the references 1(c) to 1(d) by using commercially available 5-(bromomethyl)-4-methyl-2-phenylthiazole instead of 4-(chloromethyl)-5-methyl-2-phenyloxazole in the reference 1(c). 1H-NMR(400MHz, DMSO-d6)5 ppm: 2.50(3H, s) 3.76(3H, s) 4.72(2H, d) 5.13(2H, s) 6.99(1H, dd) 7.06(1H, d) 7.14(1H, d) 7.45-7.52(3H, m) 7.85-7.91(2H, m) [0223] Reference 7 Preparation of 4-((4-(chloromethyl)phenoxy)methyl)-5-methyl-2-phenylthiazole [0224] [0225] The subject compound was prepared by performing the same operation as those of the references 1(c) to 1(d) by using 4-hydroxybenzyl alcohol instead of vanillyl alcohol in the reference 1(c). 1H-NMR(400MHz, DMSO-d6)5 ppm: 2.45(3H, s) 4.73(2H, d) 5.02(2H, s) 7.05(2H, d) 7.39(2H, d) 7.50-7.56(3H, m) 7.92-7.97(2H, m) [0226] Reference 8 Preparation of 4-((5-(chloromethyl)-2-methoxyphenoxy)methyl)-2-(furan-2-yl)-5- methyloxazole [0227] [0228] The subject compound was prepared by performing the same operation as those of the references 1(a) to 1(d) by using furfural instead of benzaldehyde in the reference 1(a), and by using 3-hydroxy-4-methoxybenzyl alcohol instead of vanillyl alcohol used in the reference 1(c). 1H-NMR(400MHz, DMSO-d6)8 ppm: 2.42(3H, s) 3.76(3H, s) 4.71(2H, d) 4.96(2H, s) 6.71(1H, dd) 6.98(1H, dd) 6.71(1H, dd) 6.96(1H, dd) 7.02(1H, dd) 7.11(1H, d) 7.18(1H, d)7.91(lH, dd) [0229] Reference 9 Preparation of 4-(allyloxy)-9H-carbazole [0231] 138g of potassium carbonate was added to N,N-dimethylformamide (500mL) solution of 121.9g of 4-hydroxycarbazole. Under stirring, 88.6g of allyl bromide was added thereto and the reaction mixture was stirred at 80 °C for 5 hours. The reaction mixture was allowed to cool, 3.5L of water was added thereto, and extracted twice with 1L of ethyl acetate. The combined organic layer was washed with 1L of brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo. The residue was purified by NH silica gel chromatography (ethyl acetate:n-hexane=l:l), and 129g of the subject compound was prepared. 'H-NMRlyOOMHz, CDC13)5 ppm: 4.79(2H, d) 5.35(1H, dd) 5.56(1H, dd) 6.18-6.28(1H, m) 6.66(1H, d) 7.01(1H, d) 7.21-7.26(1H, m) 7.30(1H, dd) 7.34-7.41(2H, m) 7.97(1H, br) 8.35(1 H,d) [0232] Reference 10 Preparation of ethyl (R)-2-bromobutyrate [0233] BrlyCOOEt Reference 10(a) Preparation of (R)-2-bromobutyric acid [0235] [0236] 25g of D-2-aminobutyric acid and 105g of KBr were dissolved in 1.25M sulfuric acid solution (588mL) at room temperature. The solution was cooled to internal temperature of approximately -5 °C, and the solution of 25.7g of sodium nitrite was added thereto dropwise at internal temperature of approximately -5 °C to -3 °C for 1 hour. The solution was stirred at internal temperature of approximately -5 °C for 1.5 hour. The reaction mixture was extracted with ethyl acetate, washed 3 times with water, washed with brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo, the residual oil was distilled under reduced pressure, and 17.6g of the subject compound was prepared as colorless oil. bp:100 °C (9 Torr) 'H-NMRlyOOMHz, CDC13)8 ppm: 1.07(3H, t) 2.04(1H, dq) 2.13(1H, dq) 4.20(1H, t) [0237] Reference 10(b) Preparation of ethyl (R)-2-bromobutyrate 0.45mL of sulfuric acid was added to ethanol (70mL) solution of 7.0g of (R)-2-bromobutyric acid at room temperature, and refluxed for 3 hours. The reaction mixture was cooled to room temperature, and poured into ice water (140mL). The solution was extracted 3 times with ethyl acetate. The combined extract was sequentially washed with saturated sodium hydrogen carbonate solution arid brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo, and 7.47g of the subject compound was prepared as colorless oil. Optical purity 96%ee (HPLC) Column: CHIRALCEL OB-H 0.46x25cm (Daicel Chemical Industries, Ltd.) Eluate: n-hexane:2-propanol =90:10 Flow rate: 0.5mL/min Temperature: 35 °C Detection: UV 230nm 1H-NMR(400MHz, CDC13)8 ppm: 1.03(3H, t) 1.30(3H, t) 2.02(1 H, dq) 2.11(1H, dq) 4.16(1H, dd)4.24(2H, dq) [0240] Reference 11 Preparation of ethyl (S)-2-bromobutyrate [0241] BrWCOOEt [0242] The subject compound was prepared by performing the same operation as those of the references 10(a) to 10(b) by using L-2-aminobutyric acid instead of D-2-aminobutyric acid in the reference 10(a). ]H-NMR(400MHz, CDCl3)5ppm: 1.30(3H, t) 1.83(1H, d) 4.23(1H, dq) 4.35(2H, q) [0243] Reference 12 Preparation of ethyl (R)-2-bromopropionate [0244] BrlyCOOEt [0245] The subject compound was prepared by performing the same operation as that of the reference 10(b) by using commercially available (R)-2-bromopropionic acid instead of (R)-2-bromobutyric acid in the reference 10(b). [0246] Reference 13 Preparation of ethyl (S)-2-bromopropionate [0247] BrWCOOEt [0248] The subject compound was prepared by performing the same operation as that of the reference 10(b) by using commercially available (S)-2-bromopropionic acid instead of (R)-2-bromobutyric acid in the reference 10(b). [0249] Reference 14 Preparation of ethyl (R)-2-bromo-3-methylbutyrate [0250] BrlyCOOEt [0251] The subject compound was prepared by performing the same operation as those of the references 10(a) to 10(b) by using D-valine instead of D-2-aminobutyric acid in the reference 10(a). 'H-NMR(400MHz, CDC13)5 ppm: 1.04(3H, d) 1.11(3H, d) 1.30(3H, t) 2.24(1H, q) 4.06-4.14(1H, m)4.24(2H, m) [0252] Reference 15 Preparation of ethyl (S)-2-bromo-3-methylbutyrate [0253] x BrWCOOEt [0254] The subject compound was prepared by performing the same operation as those of the references 10(a) to 10(b) by using L-valine instead of for D-2-aminobutyric acid in the reference 10(a). [0255] Reference 16 Preparation of ethyl (R)-2-bromo-valerate [0256] [0257] The subject compound was prepared by performing the same operation as those of the references 10(a) to 10(b) by using D-norvaline instead of D-2-aminobutyric acid in the reference 10(a). ,H-NMR(400MHz, CDC13)S ppm: 0.95(3H, t) 1.30(3H, t) 1.33-1.54(2H, m) 1.93-2.10(2H, m) 4.16-4.27(1H, m) 4.24(3H, m) [0258] Reference 17 Preparation of ethyl (S)-2-bromo-valerate [0259] [0260] The subject compound was prepared by performing the same operation as those of the references 10(a) to 10(b) by using L-norvaline instead of D-2-aminobutyric acid in the reference 10(a). [0261] Reference 18 Preparation of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid [0263] 4.35g of potassium carbonate was added to N,N-dimethylformamide (15mL) solution of lg of 4-hydroxycarbazole and 4.72g of ethyl 2-bromo-2-methylpropionate, and stirred at 90 °C for 4 hours. The reaction mixture was allowed to cool to room temperature, ice water was added thereto thereafter, and extracted twice with ethyl acetate. The combined extract was washed with brine and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo. The residue was purified by NH silica gel chromatography (ethyl acetate:n-hexane=l:2), and ethyl 2-(9H-carbazole-4-yloxy)-2-methylpropionate was prepared. 5 N sodium hydroxide solution was added to the prepared ethanol 30mL solution of ethyl 2-(9H-carbazole-4-yloxy)-2-methylpropionate, and stirred at 70 °C for 1 hour. The reaction mixture was allowed to cool to room temperature, 1 N hydrochloric acid was added thereafter to be acidified, and extracted twice with ethyl acetate. The combined extract was washed with brine and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo. The filtrate was crystallized from diisopropylether, and isolated by filtration, washed with n-hexane, dried under reduced pressure, and 1.18g of the subject compound was prepared as yellow crystal. 1H-NMR(400MHz, DMSO-d6)5 ppm: 1.71(6H, s) 6.45(1H, d) 7.06(1H, d) 7.15(1H, ddd) 7.23(1H, dd) 7.35(1H, ddd) 7.45(1H, d) 8.20(1H, d) 11.24(1H, s) 13.10(1H, s) The subject compound was prepared by performing the same operation as that of the reference 18 by using ethyl 2-bromobutyrate instead of ethyl 2-bromo-2-methylpropionate in the reference 18. 'H-NMR(400MHz, DMSO-d6)5 ppm: 1.15(3H, t) 2.05-2.13(1 H, m) 4.89(1H, t) 6.50(1H, d) 7.07(1H, d) 7.16(1H, ddd) 7.26(1H, dd) 7.35(1H, ddd) 7.46(1H, d) 8.21(1H, d) 11.27(1 H, s) 13.03(1 H, br) [0270] Reference 21 Preparation of 2-(9H-carbazole-4-yloxy)-2-phenylacetic acid [0271] [0272] The subject compound was prepared by performing the same operation as that of the reference 18 by using ethyl a-bromophenylacetate instead of ethyl 2-bromo-2-methylpropionate in the reference 18. 'H-NMR(400MHz, DMSO-d6)5 ppm: 6.08(1H, s) 6.63(1H, d) 7.08(1H, d) 7.17(1H, ddd) 7.24(1H, dd) 7.33-7.43(2H, m) 7.44-7.51(3H, m) 7.71(2H, d) 8.31(1 H, d) 11.29(1H, s) 13.28(1 H, br) [0273] Reference 22 Preparation of 2-(9H-carbazole-4-yloxy) isovaleric acid [0274] [0275] The subject compound was prepared by performing the same operation as that of the reference 18 by using ethyl 2-bromoisovalerate instead of ethyl 2-bromo-2-methylpropionate used in the reference 18. 'H-NMR(400MHz, DMSO-d6)5 ppm: 1.16(3H, d) 1.21(3H, d) 2.15-2.45(1H, m) 4.74(1H, d) 6.48(1H, d) 7.07(1H, d), 7.15(1H, ddd) 7.25(1H, dd) 7.35(1H, ddd) 7.47(1H, d) 8.21(1H, d) 11.28(1H, s) 13.06(1H, br) [0276] Reference 23 Preparation of 2-(9H-carbazole-4-yloxy) valeric acid [0277] [0278] The subject compound was prepared by performing the same operation as that of the reference 18 by using ethyl 2-bromovalerate instead of ethyl 2-bromo-2- methylpropionate in the reference 18. 'H-NMR(400MHz, DMSO-d6)8 ppm: 0.99(3H, t) 1.57-1.68(2H, m) 1.95-2.13(2H, m) 4.92(1H, dd) 6.50(1H, d) 7.07(1H, d) 7.16(1H, ddd) 7.26(1H, dd) 7.35(1H, ddd) 7.46(1H, d) 8.19(1H, d) 11.27(1H, s) 13.03(1H, br) [0279] Reference 24 Preparation of 4-(9H-carbazole-4-yloxy) butyric acid [0280] * [0281] The subject compound was prepared by performing the same operation as that of the reference 18 by using ethyl 4-bromobutyrate instead of ethyl 2-bromo-2-methylpropionate in the reference 18. ]H-NMR(400MHz, DMSO-d6)8 ppm: 2.10-2.19(2H, m) 2.55(2H, t) 4.22(2H, t) 6.68(1H, d) 7.07(1H, d) 7.15(1H, ddd) 7.29(1H, dd) 7.34(1H, ddd) 7.45(1H, d) 8.14(1H, d) 11.25(lH,s) 12.19(1H, br) [0282] Reference 25 Preparation of 2-(9H-carbazole-4-yloxy) caproic acid [0284] The subject compound was prepared by performing the same operation as that of the reference 18 by using ethyl 2-bromocaproate instead of ethyl 2-bromo-2-methylpropionate in the reference 18. 1H-NMR(400MHz, DMSO-d6)5 ppm: 0.92(3H, t) 1.35-1.47(2H, m) 1.53-1.63(2H, m) 2.00-2.13(2H, m) 4.91(1H, dd) 6.50(1H, d) 7.07(1 H, d) 7.16(1H, ddd) 7.26(1 H, dd) 7.35(1H, ddd) 7.46(1 H, d) 8.19(1H, d) 11.27(1 H, s) 13.05(1H, br) [Q285] Reference 26 Preparation of 2-(9H-carbazole-4-yloxy) heptane acid [0286] [0287] The subject compound was prepared by performing the same operation as that of the reference 18 by using ethyl 2-bromoheptanate instead of ethyl 2-bromo-2-methylpropionate in the reference 18. 1H-NMR(400MHz, DMSO-d6)5 ppm: 0.88(3H, t) 1.20-1.43(4H, m) 1.55-1.66(2H, m) 1.97-2.13(2H, m) 4.91 (1H, dd) 6.49(1 H, d) 7.07(1 H, d) 7.15(1H, ddd) 7.25(1 H, dd) 7.35(1H, ddd) 7.46(1H, d) 8.19(1H, d) 11.27(1H, s) 13.06(1H, br) [0288] Reference 27 Preparation of 2-(9H-carbazole-4-yloxy) caprylic acid [0289] [0290] The subject compound was prepared by performing the same operation as that of the reference 18 by using ethyl 2-bromocaprylate instead of ethyl 2-bromo-2-methylpropionate in the reference 18. 'H-NMR(400MHz, DMSO-d6)8 ppm: 0.86(3H, t) 1.20-1.35(4H, m) 1.35-1.44(2H, m) 1.55-1.64(2H, m) 1.97-2.13(2H, m) 4.91(1H, dd) 6.49(1H, d) 7.07(1H, d) 7.15(1H, ddd) 7.25(1H, dd) 7.35(1H, ddd) 7.46(1H, d) 8.19(1H, d) 11.27(1H, s) 13.05(1H, br) [0291] Reference 28 Preparation of 5-(9H-carbazole-4-yloxy) valeric acid [0292] The subject compound was prepared by performing the same operation as that of the reference 18 by using ethyl 5-bromovalerate instead of ethyl 2-bromo-2-methylpropionate in the reference 18. 'H-NMR(400MHz, DMSO-d6)5 ppm: 1.77-1.87(2H, m) 1.88-1.98(2H, m) 2.37(2H, t) 4.20(2H, t) 6.68(1H, d) 7.06(1H, d) 7.14(1H, ddd) 7.27(1H, dd) 7.33(1H, ddd) 7.44(1H, d) 8.14(1 H, d) 11.23(1H, s) 12.09(1H, br) [0294] Reference 29 Preparation of 6-(9H-carbazole-4-yloxy) caproic acid [0295] [02%] The subject compound was prepared by performing the same operation as that of the reference 18 by using ethyl 6-bromocaproate instead of ethyl 2-bromo-2-methylpropionate in the reference 18. 'H-NMR(400MHz, DMSO-d6)8 ppm: 1.54-1.70(4H, m) 1.87-1.97(2H, m) 2.28(2H, t) 4.19(2H, t) 6.68(1H, d) 7.06(1H, d) 7.15(1H, ddd) 7.25(1H, dd) 7.31(1H, ddd) 7.47(1H, d)8.14(lH, d) 11.23(1H, s) 12.03(1H, br) [0297] Reference 30 Preparation of 3-(9H-carbazole-4-yloxy)-2,2-dimethylpropionic acid [0298] [0299] The subject compound was prepared by performing the same operation as that of the reference 18 by using ethyl 3-chloropivalate and potassium iodide instead of ethyl 2-bromo-2-methylpropionate in the reference 18. 1H-NMR(400MHz, CDC13)8 ppm: 1.49(6H, s) 4.24(1H, s) 6.64(1 H, d) 7.03(1H, d), 7.21(1H, ddd) 7.31 (1H, dd) 7.34-7.38(2H, m) 8.04(1 H, br) 8.26(1H, d) (proton of carboxylic acid was not observed) [0300] Reference 31 Preparation of 4-(9H-carbazole-4-yloxy)-2-methylbutyric acid [0301] [0302] The subject compound was prepared by performing the same operation as that of the reference 18 by using ethyl 4-chloro-2-methylbutyrate instead of ethyl 2-bromo-2- methylpropionate in the reference 18. 'H-NMR(400MHz, DMSO-d6)S ppm: 1.22(3H, m) 1.91-2.02(1 H, m) 2.19-2.29(1H, m) 2.69-2.79(lH, m) 4.18-4.29(2H, m) 6.69(1H, d) 7.07(1H, d) 7.15(1H, ddd) 7.29(1H, dd) 7.34(1H, ddd) 7.45(1H, d) 8.14(1H, d) 11.24(1H, s) 12.25(1H, br) Example 1 [0303] Preparation of 2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)-benzyl]- 9H-carbazole-4-yloxy} acetic acid [0304] [0305] Example 1(a) Preparation of ethyl 2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)- benzyl]-9H-carbazole-4-yloxy}acetate [0306] 18mg of sodium hydride (60%) was added to N,N-dimethylformamide (5mL) solution of 107mg of ethyl 2-(9H-carbazole-4-yloxy) acetate, and stirred at room temperature for 20 minutes. Thereafter, 144mg of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2-phenyIoxazole was added thereto, and stirred at room temperature for 1 hour. The reaction mixture was poured into water, and extracted twice with ethyl acetate. The combined extract was washed with brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo, the residue was crystallized from methanol, isolated by filtration, and washed with methanol. The residue was dried under reduced pressure, and 107mg of the subject compound was prepared as white crystal. 'H-NMR(270MHz, DMSO-d6)8 ppm: 1.27QH, t) 2.37(3H, s) 3.67(3H, s) 4.25(2H, q) 4.87(2H, s) 5.05(2H, s) 5.57(2H, s) 6.64(1H, d) 6.69(1 H, d) 6.94(1 H, d) 7.02(1H, s) 7.20-7.45(4H, m) 7.45-7.55(3H, m) 7.64(lH,d) 7.88-8.97(2H, m) 8.34(1H, d) [0308] Example 1(b) Preparation of 2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)-benzyl]-9H-carbazole-4-yloxy} acetic acid [0309] lmL of 5 N sodium hydroxide solution was added to tetrahydrofuran:methanol=l:l (l0mL) solution of 107mg of ethyl 2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)-benzyl]-9H-carbazole-4-yloxy} acetate, and stirred at room temperature for 1 hour. The reaction mixture was diluted with water, adjusted to pH3 by 1 N hydrochloric acid, and extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo. The crystals of residue were isolated by filtration with ethyl acetate-diisopropylether, dried under reduced pressure, and 74mg of the subject compound was prepared as pale yellow crystal. 'H-NMR and MS spectrum data are shown in Table 1. Example 2 [0311] Preparation of 2-{9-[4-((2-(furan-2-yl)-5-methyl-oxazole-4-yl)methoxy)-3-methoxy- benzyl]-9H-carbazole-4-yloxy} acetic acid [0312] [0313] The subject compound was prepared by performing the same operation as those of the exampes 1(a) to 1(b) by using 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-2-(furan-2-yl)-5-methyloxazole prepared by the reference 2 instedad of 4-((4- (chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2-phenyloxazole in the example 1(a). 'H-NMR and MS spectrum data is shown in Table 1. Example 3 [0314] Preparation of 2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)-benzyl]- 9H-carbazole-4-yloxy}-2-methyl-propionic acid [0315] [0316] 302mg of sodium hydride (60%) was added to N,N-dimethylformamide (30mL) solution of 924mg of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid, stirred at room temperature for 20 minutes. Thereafter, 1.31 g of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2-phenyloxazole was added thereto, and stirred at room temperature for 1 hour. The reaction mixture was poured into water, adjusted to pH3 with 1 N hydrochloric acid, and extracted twice with ethyl acetate. The combined extract was washed with brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo, the residue was purified by silica gel chromatography (chloroform:methanol=50:l), and 1.88g of the subject compound was prepared as pale yellow powder. ]H-NMR and MS spectrum data is shown in Table 1. Example 4 [0317] Preparation of (±)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)- benzyl]-9H-carbazole-4-yloxy} propionic acid [0318] [0319] The subject compound was prepared by performing the same operation as that of the example 3 by using 2-(9H-carbazole-4-yloxy) propionic acid prepared by the reference 19 instead of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid used in the example 3. 'H-NMR and MS spectrum data is shown in Table 1. Example 5 [0320] Preparation of (±)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)- benzyl]-9H-carbazole-4-yloxy} butyric acid [0322] The subject compound was prepared by performing the same operation as that of the example 3 by using 2-(9H-carbazole-4-yloxy) butyric acid prepared by the reference 20 instead of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid used in the example 3. 'H-NMR and MS spectrum data is shown in Table 1. Example 6 [0323] Preparation of (±)-2-{9-[4-((2-(furan-2-yl)-5-methyl-oxazole-4-yl)methoxy)-3-methoxy- benzyl]-9H-carbazole-4-yloxy} -2-phenylacetic acid [0324] [0325] The subject compound was prepared by performing the same operation as that of the example 3 by using 2-(9H-carbazole-4-yloxy)-2-phenylacetic acid prepared by the reference 21 instead of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid used in the example 3, and using 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-2-(furan-2-yl)-5-methyloxazole prepared by the reference 2 instead of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2-phenyloxazole. 'H-NMR and MS spectrum data is shown in Table 1. Example 7 [0326] Preparation of 2-{9-[4-((2-(furan-2-yl)-5-methyl-oxazole-4-yl)methoxy)-3-methoxy- benzyl]-9H-carbazole-4-yloxy}2-methyl-propionic acid [0327] [0328] The subject compound was prepared by performing the same operation as that of the example 3 by using 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-2-(furan-2-yl)-5-methyloxazole prepared by the reference 2 instead of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2-phenyloxazole used in the example 3. 1 H-NMR and MS spectrum data is shown in Table 1. Example 8 Preparation of 2-{9-[3-methoxy-4-((5-methyl-2-(thiophene-2-yl)-oxazole-4- yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}-2-methyl-propionic acid [0330] [0331] The subject compound was prepared by performing the same operation as that of the example 3 by using 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-2-(thiophene-2-yl)-5-methyloxazole prepared by the reference 3 instead of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2-phenyloxazole used in the example 3. 'H-NMR and MS spectrum data is shown in Table 1. Example 9 [0332] Preparation of 2- {9-[3-methoxy-4-((5-methyl-2-(pyridine-4-yl)-oxazole-4-yl)methoxy)- benzyl]-9H-carbazole-4-yloxy}-2-methyl-propionic acid [0334] The subject compound was prepared by performing the same operation as that of the example 3 by using 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-2-(pyridine-4-yl)-5 methyloxazole prepared by the reference 4 instead of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2-phenyloxazole used in the example 3. ]H-NMR and MS spectrum data is shown in Table 1. Example 10 [0335] Preparation of (±)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)- benzyl]-9H-carbazole-4-yloxy}-3-methyl-butyric acid [0336] [0337] The subject compound was prepared by performing the same operation as that of the example 3 by using 2-(9H-carbazole-4-yloxy) isovaleric acid prepared by the reference 22 instead of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid used in the example 3. !H-NMR and MS spectrum data is shown in Table 1. Example 11 [0338] Preparation of (±)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)- benzyl]-9H-carbazole-4-yloxy} valeric acid [0339] [0340] The subject compound was prepared by performing the same operation as that of the example 3 by using 2-(9H-carbazole-4-yloxy) valeric acid prepared by the reference 23 instead of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid used in the example 3. !H-NMR and MS spectrum data is shown in Table 1. Example 12 Preparation of 4-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)-benzyl]- 9H-carbazole-4-yloxy} butyric acid [0342] The subject compound was prepared by performing the same operation as that of the example 3 by using 4-(9H-carbazole-4-yloxy) butyric acid prepared by the reference 24 instead of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid used in the example 3. 'H-NMR and MS spectrum data is shown in Table 1. Example 13 [0343] Preparation of 2-methyl-2-{9-[4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)-benzyl]- 9H-carbazole-4-yloxy} propionic acid [0344] [0345] The subject compound was prepared by performing the same operation as that of the example 3 by using 4-((4-(chloromethyl)phenoxy)methyl)-5-methyl-2-phenylthiazole prepared by the reference 7 instead of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2-phenyloxazole used in the example 3. 'H-NMR and MS spectrum data is shown in Table 1. Example 14 [0346] Preparation of 2-{9-[3-((2-(furan-2-yl)-5-methyl-oxazole-4-yl)methoxy)-4-methoxy- benzyl]-9H-carbazole-4-yloxy}-2-methyl-propionic acid [0347] [0348] The subject compound was prepared by performing the same operation as that of the example 3 by using 4-((5-(chloromethyl)-2-methoxyphenoxy)methyl)-2-(furan-2-yl)-5-methyloxazole prepared by the reference 8 instead of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2-phenyloxazole used in the example 3. !H-NMR and MS spectrum data is shown in Table 1. Example 15 [0349] Preparation of 2-{9-[3-methoxy-4-((5-methyl-2-phenyl-thiazole-4-yl)methoxy)-benzyl]- 9H-carbazole-4-yloxy} -2-methyl-propionic acid [0350] [0351] The subject compound was prepared by performing the same operation as that of the example 3 by using 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2-phenylthiazole prepared by the reference 5 instead of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyI-2-phenyloxazole used in the example 3. 'H-NMR and MS spectrum data is shown in Table 1. Example 16 [0352] Preparation of 2-{9-[3-methoxy-4-((4-methyl-2-phenyl-thiazole-5-yl)methoxy)-benzyl]- 9H-carbazole-4-yloxy}-2-methyl-propionic acid [0353] The subject compound was prepared by performing the same operation as that of the example 3 by using 5-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-4-methyl-2-phenylthiazole prepared by the reference 6 instead of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2-phenyloxazole used in the example 3. 'H-NMR and MS spectrum data is shown in Table 1. Example 17 [0355] Preparation of (±)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)- benzyl]-9H-carbazole-4-yloxy} caproic acid [0356] [0357] The subject compound was prepared by performing the same operation as that of the example 3 by using 2-(9H-carbazoIe-4-yloxy) caproic acid prepared by the reference 25 instead of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid used in the example 3. 'H-NMR and MS spectrum data is shown in Table 1. Example 18 Preparation of (±)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)- benzyl]-9H-carbazole-4-yloxy} heptane acid [0359] [0360] The subject compound was prepared by performing the same operation as that of the example 3 by using 2-(9H-carbazole-4-yloxy) heptane acid prepared by the reference 26 instead of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid used in the example 3. lH-NMR and MS spectrum data is shown in Table 1. Example 19 [0361] Preparation of (±)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)- benzyl]-9H-carbazole-4-yloxy} caprylic acid [0362] [0363] The subject compound was prepared by performing the same operation as that of the example 3 by using 2-(9H-carbazole-4-yloxy) caprylic acid prepared by the reference 27 instead of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid used in the example 3. 'H-NMR and MS spectrum data is shown in Table 1. Example 20 [0364] Preparation of 5-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)-benzyl]- 9H-carbazole-4-yloxy} valeric acid [0365] The subject compound was prepared by performing the same operation as that of the example 3 by using 5-(9H-carbazole-4-yloxy) valeric acid prepared by the reference 28 instead of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid used in the example 3. 'H-NMR and MS spectrum data is shown in Table 1. Example 21 [0367] Preparation of 6-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)-benzyl]- 9H-carbazole-4-yloxy} caproic acid [0368] [0369] The subject compound was prepared by performing the same operation as that of the example 3 by using 6-(9H-carbazole-4-yloxy) caproic acid prepared by the reference 29 instead of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid used in the example 3. 'H-NMR and MS spectrum data is shown in Table 1. Example 22 [0370] Preparation of 3-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)-benzyl]- 9H-carbazole-4-yloxy} -2,2-dimethyl-propionic acid [0372] The subject compound was prepared by performing the same operation as that of the example 3 by using 3-(9H-carbazole-4-yloxy)-2,2-dimethylpropionic acid prepared by the reference 30 instead of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid used in the example 3. 'H-NMR and MS spectrum data is shown in Table 1. Example 23 [0373] Preparation of 3-{9-[4-((2-(furan-2-yl)-5-methyl-oxazole-4-yl)methoxy)-3-methoxy- benzyl]-9H-carbazole-4-yloxy}-2,2-dimethyl-propionic acid [0374] [0375] The subject compound was prepared by performing the same operation as that of the example 3 by using 3-(9H-carbazole-4-yloxy)-2,2-dimethylpropionic acid prepared by the reference 30 instead of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid used in the example 3, and using 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-2-(furan-2-yI)-5-methyloxazole prepared by the reference 2 instead of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2-phenyloxazole. 'H-NMR and MS spectrum data is shown in Table 1. Example 24 [0376] Preparation of 3-{9-[3-methoxy-4-((5-methyl-2-(thiophene-2-yl)-oxazole-4- yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}-2,2-dimethyl-propionic acid [0377] [0378] The subject compound was prepared by performing the same operation as that of the example 3 by using 3-(9H-carbazole-4-yloxy)-2,2-dimethylpropionic acid prepared by the reference 30 instead of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid used in the example 3, and using 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-2-(thiophene-2-yl)-5-methyloxazole prepared by the reference 3 instead of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2-phenyloxazole. 'H-NMR and MS spectrum data is shown in Table 1. Example 25 [0379] Preparation of 3-{9-[3-methoxy-4-((5-methyl-2-pyridine-4-yl-oxazole-4-yl)methoxy)- benzyl]-9H-carbazole-4-yloxy} -2,2-dimethyl-propionic acid [0380] [0381] The subject compound was prepared by performing the same operation as that of the example 3 by using 3-(9H-carbazole-4-yloxy)-2,2-dimethylpropionic acid prepared by the reference 30 instead of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid used in the example 3, and using 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-2-(pyridine-4-yl)-5 methyloxazole prepared by the reference 4 instead of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2-phenyloxazole. ]H-NMR and MS spectrum data is shown in Table 1. Example 26 Preparation of (±)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)- benzyl]-9H-carbazole-4-yloxy} -2-phenylacetic acid [0383] The subject compound was prepared by performing the same operation as that of the example 3 by using 2-(9H-carbazole-4-yloxy)-2-phenylacetic acid prepared by the reference 21 instead of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid used in the example 3. 'H-NMR and MS spectrum data is shown in Table 1. Example 27 [0384] Preparation of (±)-4-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)- benzyl]-9H-carbazole-4-yloxy} -2-methyl-butyric acid [0385] The subject compound was prepared by performing the same operation as that of the example 3 by using 4-(9H-carbazole-4-yloxy)-2-methylbutyric acid prepared by the reference 31 instead of 2-(9H-carbazole-4-yloxy)-2-methylpropionic acid used in the example 3. 'H-NMR and MS spectrum data is shown in Table 1. Example 28 [0387] Preparation of sodium 2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)- benzyl]-9H-carbazole-4-yloxy}-2-methyl-propionate [0388] [0389] 1.88g of 2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}-2-methyl-propionic acid was suspended in 30mL of 2-propanol, and dissolved at 70 °C. 3.3mL of 1 N sodium hydroxide solution was added thereto and stirred for 0.5 hour. The reaction mixture was allowed to cool, the precipitate crystal was isolated by filtration, washed with 2-propanol, dried under reduced pressure, and 1.66g of the subject compound was prepared as white crystal. 1 H-NMR and MS spectrum data is shown in Table 1. Examples 29-37 Compounds of the table were prepared in the same way as the example 28. [0391] Example 38 Preparation of sodium (S)-(+)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4- yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}butyrate [0392] 6.05g of sodium hydride (60.) was added to N,N-dimethylformamide (170mL) solution of 35g of 4-(allyloxy)-9H-carbazole while being cooled in an ice bath, and stirred at room temperature for 1 hour. Thereafter, 49.4g of 4-((4-(chloromethyl)-2-methoxyphenoxy)methyl)-5-methyl-2-phenyloxazole was added thereto, and stirred for 1 hour. The reaction mixture was diluted with mixture of ethyl acetate:n-hexane=l:l (340mL), poured into ice water (680mL), and stirred for 1 hour. The crystalline precipitate was isolated by filtration, and washed with mixture of ethyl acetate:n-hexane=l:l. The crystalline precipitate was dried under reduced pressure, and 55.4g the subject compound was prepared as pale yellow crystal. 1H-NMR(400MHz, CDC13)5 ppm: 2.35(3H, s) 3.69(3H, s) 4.82(2H, ddd) 4.97(2H,s) 5.37(1H, ddt) 5.43(2H,s) 5.58(lH,ddt) 6.26(1H, ddt) 6.63(lH,dd) 6.69(1H, d) 6.71 (lH,d) 6.90(1 H,d) 7.00(1 H,d) 7.22-7.44(7H, m) 7.97-8.00(2H, m) 8.40(lH,d) [0396] Example 38(b) Preparation of 9-{4-[(5-methyl-2-phenyloxazole-4-yl)methoxy]-3-methoxybenzyl}-9H- carbazole-4-ol [0397] l0g of 9-{4-[(5-methyl-2-phenyloxazole-4-yl)methoxy]-3-methoxybenzyl} -4-(allyloxy)-9H-carbazole was suspended in mixed solution (70mL) of tetrahydrofuran-ethanol=4:l, 986mg of triphenylphosphine, 84mg of palladium acetate, and 2.1mL of formic acid were added, and refluxed for 5 hours. The reaction mixture was allowed to cool, and then concentrated in vacuo, and the residue was crystallized from lOmL of ethanol. The crystalline precipitate was isolated by filtration, washed with ethanol, dried under reduced pressure, and 8.96g of the subject compound was prepared as pale yellow crystal. 1H-NMR(400MHz, DMSO-d6)8 ppm: 2.37(3H, s) 3.67(3H, s) 4.87(2H,s) 5.51(2H,s) 6.55(1H, dd) 6.62(lH,d) 6.94(lH,d) 7.02(1 H,d) 7.07(1H, d) 7.16(1H, dd) 7.21(1H, dd) 7.36(1H, ddd) 7.47-7.54(3H, m) 7.58(1H, d) 7.88-7.94(2H, m) 8.19(lH,d) 10.12(1H, s) [0399] Example 38(c) Preparation of ethyl (S)-(+)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4- yl)methoxy)-benzyl]-9H-carbazole-4-yloxy} butyrate [0400] Preparation of sodium (S)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazoIe-4-yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}-3-methyl-butyrate [0412] [0413] The subject compound was prepared by performing the same operation as those of the examples 38(c) to (e) by using ethyl (R)-2-bromo-3-methylbutyrate prepared by the reference 14 instead of ethyl (R)-2-bromobutyrate used in the example 38(c). Optical purity 94%ee (HPLC). Column: CHIRALCEL OD-H 0.46*25cm (Daicel Chemical Industries, Ltd.) Eluate: (n-hexane:2-propanol =80:10)+0.1. trifluoroacetic acid Flow rate: 0.8mL/min Temperature: 40 °C Detection: UV 230nm 'H-NMR and MS spectrum data is shown in Table 1. [0414] Example 41 Preparation of sodium (S)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4- yl)methoxy)-benzyl]-9H-carbazole-4-yloxy} valerate of the examples 38(c) to (e) by using ethyl (S)-2-bromo-propionate prepared by the reference 13 instead of ethyl (R)-2-bromobutyrate used in the example 38(c). Optical purity 98%ee (HPLC). 'H-NMR and MS spectrum data is shown in Table 1. [0423] Example 44 Preparation of sodium (R)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4- yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}-3-methyl-butyrate [0424] [0425] The subject compound was prepared by performing the same operation as those of the examples 38(c) to (e) by using ethyl (S)-2-bromo-3-methylbutyrate prepared by the reference 15 instead of ethyl (R)-2-bromobutyrate used in the example 38(c). Optical purity 98%ee (HPLC). 'H-NMR and MS spectrum data is shown in Table 1. [0426] Example 45 Preparation of sodium (R)-2-{9-[3-methoxy-4-((5-methyl-2-phenyI-oxazoIe-4-yl)methoxy)-benzyI]-9H-carbazole-4-yloxy} valerate [0427] [0428] The subject compound was prepared by performing the same operation as those of the examples 38(c) to (e) by using ethyl (S)-2-bromo-valerate prepared by the reference 17 instead of ethyl (R)-2-bromobutyrate used in the example 38(c). Optical purity 97%ee (HPLC). 'H-NMR and MS spectrum data is shown in Table 1. [0429] Example 46 Preparation of sodium 4-((9-(4-((5-methyl-2-phenyloxazole-4-yl)methoxy)-3- methoxybenzyl)-9H-carbazole-5-yloxy)methyl) benzoate [0431] Example 46(a) Preparation of ethyl 4-((9-(4-((5-methyl-2-phenyloxazole-4-yI)methoxy)-3- methoxybenzyl)-9H-carbazole-5-yloxy)methyl) benzoate [0432] [0433] 47mg of methyl 2-bromomethylbenzoate and 27mg of potassium carbonate (powder) were added to N,N-dimethylformamide (2mL) solution of 98mg of 9-{4-[(5- methyl-2-phenyloxazole-4-yl)methoxy]-3-methoxybenzyl}-9H-carbazole-4-ol, and stirred at 90 °C for 1 hour. After the reaction mixture was allowed to cool, water was added thereto, and then extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo, the residue was crystallized from a small amount of ethanol, isolated by filtration with n-hexane, dried under a reduced pressure, and 1 l0mg of the subject compound was prepared. 'H-NMRly00MHz, DMSO-d6)5 ppm: 2.33(3H,s) 3.67(3H,s) 3.87(3H,s) 4.87(2H,s) 5.49(2H, s) 5.57(2H, s) 6.54(lH,dd) 6.86(lH,d) 6.94(lH,d) 7.04(1H, d) 7.20(1 H, dd) 7.29(1 H, d) 7.37(1H, dd) 7.40(1H, ddd) 7.48-7.53(3H, m) 7.65(1H, d) 7.75(2H, d) 7.88-7.93(2H, m) 8.05(2H.d) 8.16(lH,d) [0434] Example 46(b) Preparation of sodium 4-((9-(4-((5-methyl-2-phenyloxazole-4-yl)methoxy)-3- methoxybenzyl)-9H-carbazole-5-yloxy)methyl) benzoate [0435] [0436] lmL of 5 N sodium hydroxide solution was added to tetrahydrofuran: methanol=l:l(20mL) solution of 1 l0mg of ethyl 4-((9-(4-((5-methyl-2-phenyloxazole-4- yl)methoxy)-3-methoxybenzyl)-9H-carbazole-5-yloxy)methyl) benzoate, and stirred at 70 °C for 1 hour. The reaction mixture was allowed to cool, and the water was added thereto. The crystalline precipitate was isolated by filtration, and washed with 2-propanol. The collected precipitate was dried under reduced pressure, and 107mg of the subject compound was prepared as white crystal. "H-NMR and MS spectrum data is shown in Table 1. [0437] Example 47 Preparation of sodium 2-{9-[3-methoxy-4-((5-methyl-2-phenyloxazole-4-yl)methoxy)- benzyl]-9H-carbazole-4-yloxy} benzoate [0438] [0439] Example 47(a) Preparation of 2-{9-[3-methoxy-4-((5-methyl-2-phenyloxazole-4-yl)methoxy)-benzyl]- 9H-carbazole-4-yloxy} benzoic acid [0441] 3.53g of 2-bromobenzoic acid, 2.23g of copper iodide, 1.63g of N,N-dimethylglycine hydrochloride, and 15.2g of cesium carbonate were added to 1,4-dioxane (50mL) suspension of 5.74g of 9-{4-[(5-methyl-2-phenyloxazole-4-yl)methoxy]-3-methoxybenzyl}-9H-carbazole-4-ol, and refluxed overnight. 1 N hydrochloric acid was added to the reaction mixture, extracted with ethyl acetate, and washd with brine. The extract was dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo, the residu was purified by silica gel chromatography (ethyl acetate:n-hexane=2:l), and 1.4g of the subject compound was prepared as white crystal. ,H-NMR(400MHz, DMSO-d6)8 ppm: 2.38(3H,s) 3.69(3H,s) 4.88(2H,s) 5.62(2H,s) 6.57(lH,d) 6.61(lH,dd) 6.97(2H,d) 7.07(lH,d) 7.15(lH,dd) 7.26(lH,ddd) 7.37-7.54(7H,m) 7.69(lH,d) 7.88-7.93(3H,m) 8.09(lH,d) 12.91(lH,s) [0442] Example 47(b) Preparation of sodium 2-{9-[3-methoxy-4-((5-methyl-2-phenyloxazole-4-yl)methoxy)- benzyl]-9H-carbazole-4-yloxy} benzoate [0444] 260|xl of 5 N sodium hydroxide solution was added to 2-propanol suspension of 395mg of 2-{9-[3-methoxy-4-((5-methyl-2-phenyloxazole-4-yl)methoxy)-benzyl]-9H-carbazole-yloxy-benzoic acid, and was dissolved by heating. The insoluble was filtered off, and the filtrate was concentrated in vacuo. The residue was crystallized from ethanol, isolated by filtration with n-hexane, and dried under reduced pressure, and 395mg of the subject compound was prepared as white crystal. 'H-NMR and MS spectrum data is shown in Table 1. [0445] Example 48 Preparation of sodium 3-{9-[3-methoxy-4-((5-methyI-2-phenyloxazole-4-yl)methoxy)- benzyl]-9H-carbazole-4-yloxy} benzoate [0446] The subject compound was prepared by performing the same operation as those of the examples 47(a) to 47(b) by using 3-bromobenzoic acid instead of 2-bromobenzoic acid used in the example 47(a). ]H-NMR and MS spectrum data is shown in Table 1. [0448] Example 49 Preparation of sodium 4-{9-[3-methoxy-4-((5-methyl-2-phenyloxazole-4-yl)methoxy)- benzyl]-9H-carbazole-4-yloxy} benzoate [0449] [0450] The subject compound was prepared by performing the same operation as those of the examples 47(a) to 47(b) by using 4-bromobenzoic acid instead of 2-bromobenzoic acid used in the example 47(a). 'H-NMR and MS spectrum data is shown in Table 1. [0451] Example 50 Preparation of sodium (+)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4- yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}-2-phenylacetate [0452] [0453] Example 50(a) Preparation of sodium (±)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4- yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}-2-phenylacetate [0454] [0455] 5.26g of ethyl a-bromophenylacetate and 4.23g of potassium carbonate (powder) were added to N,N-dimethylformamide (50mL) suspension of 10.Og of 9-{4-[(5-methyl- 0.5 N sodium hydroxide solution (3.1mL) was added to the solution of 980mg of (+)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}-2-phenylacetic acid in 2-propanol (30mL). 2-propanol was removed under reduced pressure, the residue was collected by filtration with a small amount of 2-propanol, and 850mg of the subject compound was prepared as pale brown powder. Optical purity>99.ee (HPLC) Column: CHIRALPAK AD-H 0.46x15cm (Daicel Chemical Industries, Ltd.) Eluate: (n-hexane:2-propanol =80:20)+0.1% trifluoroacetic acid Flow rate: 0.8mL/min Temperature: 40 °C Detection: UV 230nm [a]D27+31.8°(c 1.02, MeOH) 'H-NMR and MS spectrum data is shown in Table 1. [0468] Example 51 Preparation of sodium (-)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4- yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}-2-phenylacetate [0469] phenyl-oxazoIe-4-yl)methoxy)-benzyl]-9H-carbazole-4-yloxy} -2-phenylacetic acid was prepared as pale brown powder. [0473] Example 51(b) Preparation of sodium (-)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4- yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}-2-phenylacetate [0474] [0475] The same operation as that of the example 50(d) was carried out by using 750mg of (-)-2-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)-benzyl]-9H- carbazole-4-yloxy}-2-phenylacetic acid and 750mg of the subject compound was prepared as pale brown powder. Optical purity 98.ee (HPLC) Column: CHIRALPAK AD-H 0.46x15cm (Daicel Chemical Industries, Ltd.) Eluate: (n-hexane:2-propanol =80:20)+0.1. trifluoroacetic acid Flow rate: 0.8mL/min Temperature: 40 °C Detection: UV 230nm [a]D27-35.1°(cl.03, MeOH) 'H-NMR and MS spectrum data is shown in Table 1. [0476] Example 52 Preparation of sodium (-)-4-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4- yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}-2-methyl-butyrate [0477] [0478] Example 52(a) Preparation of (S)-3-(4-(9-(4-((5-methyl-2-phenyloxazole-4-yl)methoxy)-3- methoxybenzyl)-9H-carbazole-4-yloxy)-2-methoxybutanoyl)-4-benzyloxazolidine-2-one [0480] 2.2mL of oxalyl chloride was added to the solution of lO.Og of (±)-4-{9-[3- methoxy-4-((5-methyl-2-phenyloxazole-4-yl)methoxy)-benzyl]-9H-carbazole-4-yIoxy}-2-methyl-butyric acid prepared by the example 27 in 1,2-dichloroethane (lOOmL), and then 5 drops of N,N-dimethylformamide was added thereto, and stirred at room temperature for 1 hour. The reaction mixture was vacuum concentrated, and (±)-4-(9-(4-((5-methyl-2-phenyloxazole-4-yl)methoxy)-3-methoxybenzyl)-9H-carbazole-4-yloxy)-2-methylbutanoyl chloride was prepared. [0481] 9.1mL of 2.44M n-butyllithium tetrahydrofuran solution was added thereto dropwise into the solution of 3.59g of (S)-4-benzyl-2-oxazolidinone in tetrahydrofuran (50mL) at -50 °C. The solution was stirred at -50 °C for 1 hour. Thereafter, the solution of the previously prepared (±)- 4-(9-(4-((5-methyl-2-phenyloxazole-4-yl)methoxy)-3-methoxybenzyl)-9H-carbazole-4-yloxy)-2-methylbutanoyl chloride in tetrahydrofuran (50mL) was added thereto dropwise at -50 °C. After the dropwise addition thereto, the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo, and diastereomer mixture was prepared as crystal. The crystal was isolated by filtration with ethyl acetate-n-hexane, and 3.19g of the subject compound (compound A) of single diastereomer (less polar) was prepared. The filtrate was concentrated in vacuo, the concentrated residue was purified by medium-pressure silica gel chromatography (ethyl acetate:n-hexane=5:l), and 3.3g of the subject compound (compound B) of the other diastereomer (polar) was prepared as powder. [0482] Example 52(b) Preparation of optically active 4-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4- yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}-2-methyl-butyric acid [0483] [0484] 1.8lg of 30. hydrogen peroxide solution was added to the solution (75mL) of 3.00g of (S)-3-(4-(9-(4-((5-methyl-2-phenyloxazole-4-yl)methoxy)-3-methoxybenzyl)-9H-carbazole-4-yloxy)-2-methoxybutanoyl)-4-benzyloxazolidine-2-one (compound B) prepared by the example 52(a) in tetrahydrofuran:water=4:l at -5 °C, and then 6.4mL of 1M lithium hydroxide solution was added thereto dropwise. After the dropwise addition thereto, the solution was stirred for 30 minutes, and 1M sodium sulfite solution was added to the reaction mixture. Thereafter, the pH was adjusted to pH3 with 1 N hydrochloric acid, and extracted with ethyl acetate. The extract was washed with brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated in vacuo, the residue was crystallized from ethyl acetate, filtered off with diisopropylether, and 2.1g of the optically active 4-{9-[3-methoxy-4-(5-methyl-2-phenyl-oxazole-4-ylmethoxy)-benzyl]-9H-carbazole-4-yloxy}-2-methyl-butyric acid was prepared as white crystal. [0485] Example 52(c) Preparation of sodium (+)-4-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4- yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}-2-methyl-butyrate [0486] [0487] Sodium 2-ethylhexanoate (479mg) was added to the solution of 1.5g of 4-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4-yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}-2-methyl-butyric acid prepared by the example 52(b) in ethyl acetate (15mL) at room temperature. After stirring at room temperature for 30 minutes, the precipitate was isolated by filtration, washed with ethanol, dried under reduced pressure, and 1.49g of the subject compound was prepared as white powder. Optical purity>99.ee (HPLC) Column: CH1RALPAK AD-H 0.46x15cm (Daicel Chemical Industries, Ltd.) Eluate: (n-hexane:2-propanol =80:20)+0.1. trifluoroacetic acid Flow rate: 0.8mL/min Temperature: 40 °C Detection: UV230nm [a]D25-16.2°(c0.45, MeOH) 'H-NMR and MS spectrum data is shown in Table 1. [0488] Example 53 Preparation of sodium (+)-4-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4- yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}-2-methyl-butyrate [0489] [0490] Example 53(a) Preparation of optically active 4-{9-[3-methoxy-4-((5-methyl-2-phenyl-oxazole-4- yl)methoxy)-benzyl]-9H-carbazole-4-yloxy}-2-methyl-butyric acid sets: hRXRa-Fl: 5'-ACG AAT TCA GTT AGT CGC AGA CAT GGA C-3' (Sequence number: 5); and hRXRa-Rl: 5'-GTT CTA GAG CAG GCC TAA GTC ATT TGG T-3' (Sequence number: 6); that were designed based on human RXRa gene sequence (Genbank accession No. NM002957) with human liver cDNA library (manufactured by Takara Shuzo) used as template. For PCR reaction, TaKaRa LA Taq polymerase (manufactured by Takara Shuzo) was used. First, 10 μ1 of 10> A tube including above-mentioned reaction mixture was set in the iCycler™ Thermal Cycler (manufactured by BIO-RAD Laboratories, Inc.), and then processed at 95 °C for 2 minutes. Moreover, after repeating 35 cycles of 20 seconds at 95 °C and 2 minutes at 68 °C, the process was carried out at 72 °C for 5 minutes. The PCR product prepared by the PCR reaction was provided with an agarose gel (1%) electrophoresis, 1.4 kb of DNA fragment including human RXRa gene was collected from the gel by using a PCR purification system (manufactured by Promega Corporation). Thereafter, the DNA fragment was processed with 2 kinds of restriction enzymes, EcoRI and Xbal, and inserted into EcoRI-Xbal site of pCI-neo vector (manufactured by Promega Corporation), whereby plasmid pCI-hRXRa was prepared. [0508] Reference 4a (Preparation of reporter plasmid) A DNA fraction including PPAR responsive element (PPRE) of rat Acyl-CoA oxidase was prepared using the following DNA: PPRE-F1: 5'-TCG ACA GGG GAC CAG GAC AAA GGT CAC GTT CGG GAG-3' (Sequence number: 7) and PPRE-R1: 5'-TCG ACT CCC GAA CGT GAC CTT TGT CCT GGT CCC CTG-3' (Sequence number: 8). First, PPRE-F1 and PPRE-R1, after annealing, were inserted into Sail site of a plasmid pUC18 (manufactured by Takara Shuzo). By determining the base sequence of the inserted fraction, a plasmid pUC-PPRE3 in which 3 PPREs are tandem-linked is selected. Subsequently, pRL-TK vector (manufactured by Promega Corporation) was cut with restriction enzymes, Bglll and Hindlll, provided with an agarose gel (1%) the carbazole derivative, solvate thereof, or pharmaceutical^ acceptable salt thereof according to any one of claims 1 to 11; and a pharmaceutical^ acceptable carrier. 13. A preventive agent and/or therapeutic agent for metabolic syndrome including the carbazole derivative, solvate thereof, or pharmaceutical^ acceptable salt thereof according to any one of claims 1 to 11 as an active ingredient. 14. A preventive agent and/or therapeutic agent for fatty liver, obesity, lipid metabolism abnormality, visceral adiposity, diabetes, hyperlipemia, impaired glucose tolerance, hypertension, non-alcoholic fatty liver disease, or non-alcoholic steatohepatitis, the agent including the carbazole derivative, solvate thereof, or pharmaceutical^ acceptable salt thereof according to any one of claims 1 to 11 as an active ingredient. 15. A preventive agent and/or therapeutic agent for fatty liver or obesity including the carbazole derivative, solvate thereof, or pharmaceutical^ acceptable salt thereof according to any one of claims 1 to 11 as an active ingredient. 16. A PPAR modulator including the carbazole derivative, solvate thereof, or pharmaceutical^ acceptable salt thereof according to any one of claims 1 to 11 as an active ingredient. 17. A PPARy antagonist including the carbazole derivative, solvate thereof, or pharmaceutical^ acceptable salt thereof according to any one of claims 1 to 11 as an active ingredient. 18. A usage of the carbazole derivative, solvate thereof, or pharmaceutical^ acceptable salt thereof according to any one of claims 1 to 11 for preparing a preventive agent and/or therapeutic agent for fatty liver, obesity, lipid metabolism abnormality, visceral adiposity, diabetes, hyperlipemia, impaired glucose tolerance, hypertension, non-alcoholic fatty liver disease, or non-alcoholic steatohepatitis. 19. A carbazole derivative, solvate thereof, or pharmaceutical^ acceptable salt thereof, the carbazole derivative represented by the following general formula (I"):

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