Title of Invention	ACTIVATOR OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR 8
Abstract	ABSTRACT A compound represented by the formula (I) or a salt of the compound, and a PPAR-5 activator which contains the compound or salt as the active ingredient: Ci^Q alkyl, C2-g alkenyl, etc.; each of R^ and R^ repre¬sents hydrogen, C^^.g alkyl, etc.; and R^ represents hydro¬gen, etc.; provided that each of Z and R3 is attached to the benzene ring, and X^ is not attached to the benzene ring).

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SPECIFICATION ACTIVATOR OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR S 1 1 '[Technical field] The present invention relates to an activator of peroxisome proliferator activated receptor 5. [Prior art] The peroxisome is a small organ present in cells of animals and plants, and its matrix contains various en¬zymes such as catalases. Various compounds such as fi-brates, herbicides, and phthalic acid plasticizers are known as peroxisome proliferators which induce prolifera¬tion of peroxisomes, Isseman, et al. have identified a nuclear receptor which is activated by peroxisome proliferator and called it peroxisome proliferator activated receptor (PPAR). Nature, 347, p645-650, 1990. Three subtypes such as PPARa, PPARy and PPAR6 have been identified. Proc. Natl. Acad. Sci. USA, 91, p7335-7359, 1994. The above-mentioned fibrates used as the serum triglyceride (TG) lowering drug can modulates PPAR6 activ¬ity. Further, thiazolidine compounds {Troglitazone, Rosiglitazone, Pioglitazone) useful in the treatment of diabetes are also known as ligands of PPAR-y. It is reported that several compounds such as GW-2433 (Glaxo Wellcome), L-I65041 (Merck), and yM-16638 (Yamanouchi Pharmaceutical) activate PPAR5. Each formula is as follows: vy Ho-V-^0 CO2H YM-16638 WO 92/10468 describes that GW-2433 can be used for prevention and treatment of atherosclerosis. WO 97/28115 describes that L-165041 can be used for treatment of diabetes and suppression of obesity. WO 99/04815 describes that YM-16638 shows effects for reducing serum cholesterol and reducing LDL choles¬terol . Recently, JBC, 272(6), p3406-341D, 1997 and Cell, 99, p335-345, 1999 describe proposal for application of PPAR 6 ligand as an anti-cancer agent and an anti-inflam¬matory agent. The following compounds A to E have a structure similar to the compound of the present invention (men¬tioned below) , in rdore detail a benzisoxazole derivative of the general formula (I). The compound A is disclosed in Japanese Patent No. 2,581,523, the compound B is dis¬closed in WO 98/28254, the compound C is disclosed in Japanese Patent Provisional Publication No. 8(1996)-311065, the compound D is disclosed in WO 97/27190, and the compound E is disclosed in WO 96/20935. Each formula is as follows: C02H Compound A OEt CO2H Compound B Compound C ^^"S-^N t-Bu Md Me O^^COsH Compound D Compound E In the compounds A, B and C, carboxyl or cyano is linked by an alkylene chain (which can be substituted with ethoxy or propylthio at the a-position) to the right side of the benzisoxazole or benzofuran ring. The compound of the invention has a structure dif¬ferent from the compounds A, B and C. In the compound of the invention, acetic acid or a 2-alkylpropionic acid is linked by an ether or thioether bond to the 5th to 7th position of the benzisoxazole ring. It has been reported that the compounds A, B and C have an effect of improving insulin resistance or de¬creasing blood glucose. However, no mention is given with respect to an effect as PPARS ligand. In the compound D, benzofuran ring is linked by an alkylene chain to the 1st position of the indole ring. The compound of the invention has a structure different from the compound D. In the compound of the invention, the thiazole or oxazole ring is linked by an alkylene chain to the 3rd position of the benzisoxazole ring. WO 97/27190 describes that the ACAT (acyl coenzyme A - cho¬lesterol acyltransferase). However, no mention is given with respect to an effect as PPARS ligand. In the compound E, the oxazole ring is substituted with only phenethyl at 4th position, and the benzene ring moiety of the benzofuran ring has only methoxycarbonyl- raethoxy. The compound of the invention has a structure different from the compound E. In the compound of the in¬vention, the oxazole (or thiazole) ring has two substitu-ent groups such as a substituted phenyl and isopropyl, and the benzene ring moiety of the benzofuran ring (ben-zisoxazole ring) has a substituent group such as propyl, propenyl in addition to alkoxy substituted with carboxyl. WO 96/20935 describes that the compound E has an antago¬nistic effect against TXA2 receptor. However, no mention is given with respect to an effect as PPAR5 ligand. The present inventors have been filed WO 01/79197, which relates to benzisoxazole derivatives. In the com¬pounds of the Examples in the patent application, the benzisoxazole ring has no substituent. On the other hand, the compound of the present invention has benzisoxazole ring having at least one substituent. An object of the present invention is to provide a compound having the following general formula (I), which has an effect of activating peroxisome proliferator acti¬vated receptor 5. [Disclosure of invention] The invention resides in a compound having the fol¬lowing general formula (I) or a salt thereof: 1 N- (wherein A is 0, S or NR^ in which R^ is hydrogen or Cj^_g alkyl; B^ is CW or N in which W is hydrogen or a bond; B2 is 0, S or NRS in which R^ is hydrogen or C^.g al¬kyl; each of X^ and X2 is 0, S, NH, NHC{=0), C(=0), C (=N-0R9, CH(0R^°), C=C, C=C or a bond in which each of R^ and RIO is hydrogen or C^.g alkyl; y is a C]^_g alkylene chain, which can be substituted with C]^_8 alkyl or C^^g alkyl substituted with 1-3 halo¬gens; Z is NH, 0 or S R^ is aryl, which can be substituted with a group or atom selected from the group consisting of C^^.g alkyl, C^. g alkoxy, C^.g alkyl substituted with 1-3 halogens, hy-droxyl, nitro, amino, phenyl, pyridyl and halogen, or a heterocyclic group having five to eight membered ring comprising one to three hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur and the other atoms consisting of carbon (benzene ring can be condensed with the heterocyclic ring); R2 is C2-g alkyl, C^.g alkyl substituted with 1-3 halogens, €3.7 cycloalkyl, C2-8 alkenyl, C2_g alkynyl, al¬kyl (comprising C]^_4 alkyl moiety) substituted with aryl, which can be substituted with a group or atom selected from the group consisting of C^.g alkyl, C]^_g alkoxy, C^.g alkyl substituted with 1-3 halogens, hydroxyl, nitro, amino, phenyl, pyridyl and halogen, or alkyl (comprising C2_4 alkyl moiety) substituted with a heterocyclic group having five to eight membered ring (comprising one to three hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur and the other atoms consist¬ing of carbon); R3 is halogen, trifluoromethyl, C^.g alkyl, C2-g al¬kenyl or C2_e alkynyl; each of R^ and R^ is hydrogen, C^.g alkyl or Cj^.g al¬kyl substituted with 1-3 halogens; and R^ is hydrogen, CI_Q alkyl substituted with amino, Ci_8 alkyl or alkali metal; provided that each of Z and R^ is attached to the benzene ring, and X^ is not attached to the benzene ring. The invention also provides an activator of per¬oxisome proliferator activated receptor 5, which contains as an effective component a compound of the formula (I) or a salt thereof. [Detailed description of the invention] In the formula (I), R^, R^ R^, R^, R"^, R8, R9, RIO, the substituent of the alkylene chain of Y, the substitu¬ent of the aryl and the heterocyclic group of R^, the sub¬stituent of the alkyl group substituted with aryl of R^, and the substituent of the alkyl group substituted with a heterocyclic group of R2 can be an alkyl group having 1-8 carbon atoms. Examples of the alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl and hexyl. R2 can be an alkyl group having 2-8 carbon atoms. Examples of the alkyl groups include ethyl, propyl, iso¬propyl, butyl, isobutyl, t-butyl, pentyl and hexyl. R2, R', R^, the substituent of the alkylene chain of Y, the substituent of the aryl or heterocyclic group of R^, the substituent of the alkyl group substituted with aryl of R2, and the substituent of the alkyl group substi¬tuted with a heterocyclic group of R2 can be an alkyl groups having 1-8 carbon atoms substituted with 1-3 halo¬gens. Examples of the haloalkyl groups include methyl, ethyl, propyl, isopropyl, butyl, and t-butyl which are substituted with 1-3 halogens such as fluorine, chlorine, and bromine. Trifluoromethyl, chloromethyl, 2-chloroethyl, 2-bromoethyl and 2-fluoroethyl are pre¬ferred. R2 and R3 can be an alkenyl group having 2-8 carbon atoms. Examples of the alkenyl groups include vinyl and allyl. R2 and R3 can be an alkynyl group having 2-8 carhon atoms. Examples of the alkynyl groups include propargyl. R3 can be a halogen atom. Examples of the halogen atoms include fluorine, chlorine and bromine. R2 can be a cycloalkyl group having 3-7 carbon atoms. Examples of the cycloalkyl groups include cyclopropyl, cyclopentyl and cyclohexyl. The substituent of the aryl or heterocyclic group of Ri, the substituent of the alkyl group substituted with aryl of R2, and the substituent of the alkyl group substi¬tuted with a heterocyclic group of R2 can be an alkoxy groups having 1-8 carbon atoms. Examples of the alkoxy groups include methoxy, ethoxy, propoxy, isopropoxy, bu-toxy, isobutoxy, t-butoxy, pentyloxy and hexyloxy. R1 and the aryl moiety of the aryl substituted with alkyl of R2 can be an aryl group. Examples Qf the aryl groups include phenyl and naphthyl. Ri and the substituent of the alkyl group of R^ can be a heterocyclic group having five to eight membered ring. Examples of the heterocyclic groups include pyridyl, thienyl, furyl, thiazolyl and quinolyl. R1 can be a heterocyclic group having five to eight membered ring comprising one to three hetero atoms se¬lected from the group consisting of nitrogen, oxygen and sulfur and the other atoms consisting of carbon. A ben¬zene ring can be condensed with the heterocyclic ring. Examples of the condensed rings include quinoline ring and benzothiophene ring. Y can be an alkylene chain having 1 to 3 carbon at¬oms. Examples of the alkylene chains include methylene and ethylene. R3 can be one to three groups, Two or three groups of R3 can be different from each other. R6 can be an alkyl group having 1-8 carbon atoms sub¬stituted with amino. Examples of the aminoalkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobu-tyl, t-butyl, pentyl and hexyl which are substituted with an amino group such as piperidino, pyrrolidino, dimethyl-amino, and diethylamino. (1) A preferred compound of the invention is a com¬pound of the formula (I) or salt thereof, in which Rl is attached to the 2nd position of the oxazole, thiazole or imidazole ring. (2) Another preferred compound of the invention is a compound of the formula (I), a salt thereof or (1), in which Bi is N, and B^ is 0. (3) A further preferred compound of the invention is a compound of the formula (I), a salt thereof, (l) or (2), in which R^ is hydrogen. (4) A furthermore preferred compound of the inven¬tion is a compound of the formula (I), a salt thereof, (1), (2) or (3), in which X^ is a bond. (5) A still further preferred compound of the in¬vention is a compound of the formula (I), a salt thereof, (1), (6) A still further preferred compound of the in¬vention is a compound of the formula (1), a salt thereof, (1), {2), (3), (4) or (5), in which R^ is aryl substituted with a group or atom selected from the group consisting of C-L_g alkyl, Ci^Q alkoxy, C^^g alkyl substituted with 1-3 halogens, hydroxyl, nitro, amino, phenyl, pyridyl and halogen. (7) A still further preferred compound of the in¬vention is a compound of the formula (I), a salt thereof, (1), (2), (3), (4), (5) or (6), in which R2 is C2-8 alkyl. (8) A still further preferred compound of the in¬vention is a compound of the formula {I), a salt thereof, (1), {2), (3), (4), (5), (6) or (7), in which R3 is Ci.g alkyl or C2_g alkenyl. The compound of the formula (I) can be in the form of pharmaceutically acceptable salts such as alkali metal salts, e.g., sodium salt and potassium salt. The processes for preparing the benzisoxazole de¬rivative of the formula (I) are described below. [Synthetic process 1] ^ -| x^—Y—X'- -NHj -Q' (") C, y /A A—x'—y—x^ X -ZH CW) Q-^-COiR' (HI) ^ ^_X1—Y X' ^ — 2—Tv—COiR* Hydrolysis (V) ^^ ■^ nt '■a* "VlLv. <:> Ti X'—^Y X' "o -Z—7^—CO3H R» R- (VI (In the formulas, R is an alkyl group having 1-6 carbon atoms such as methyl, ethyl, Q is a releasing group such as chlorine, bromine, and R^, R^, R3^ R4_ R5^ A, X^, Y, X2 and 2 are those described hereinbefore). The hydroxyl(or mercapto)benzisoxazole derivative of the formula (III) can be prepared by diazotizing the aminobenzisoxazole derivative of the formula (II) with sodium nitrite and a mineral acid (sulfuric acid) while cooling with ice, and decomposing the product with sulfuric acid where Z is oxygen, or reacting the product with potassium ethylxanthate and heating it where Z is sulfur. The benzisoxazole derivative of the formula (V) according to the invention can be prepared by reacting the compound of the formula (III) with the acetic ester derivative of the formula (IV) in the presence of a base such as potassium carbonate. The benzisoxazole derivative of the formula (VI) according to the invention can be prepared by subjecting the benzisoxazole derivative of the formula (V) according to the invention to hydrolysis in the presence of lithium hydroxide or potassium hydroxide. In the case that R^ is allyl, the starting material represented by the formula (III) can be synthesized according to the following reaction scheme. 'T^., \^_^x.-v-,» N, -OH • Br -KjCO, ^ 4-x^-v^x' \^ it N •^, -OH (In the formulas. A, R^, R^, X^, X2 and Y are those described hereinbefore). [Synthetic process 2] The benzisoxazole derivative of the invention can be prepared according to the following reaction scheme. Q-7^C0iH* ■if ^ fi, R5 KiCOj R3 Ra R' "-■ I N-A I LDA ^o^ ^^ Hi Rj fa R' Hydrolysis ^0-^^^ R (In the formulas. A, R^, R^, R3, R*, R^, Z, Q and R are those described hereinbefore). [Synthetic process 3] The benzisoxazole derivative of the invention can also be prepared according to the following reaction scheme. Q A CO2H' ^,^ R; R, Base ij ij-''^ OHC—n— II . —I ;—T-p-cbsR' OHC L_ H ZH __^ OHC—i^ Jl -j ^^^ Rn R'^-4_ ,PW Base A- Reduction ^ ,./J ^-^-^ \^ '^"'^^lJ-^^^°='" : ^ e- 4 ,^H,^. li f _J B2 \ "4 R5 «3 Hydrolysis R) (In the formulas, R, Q, R^, R^, R3. R^, RS, B^, A and Z are those described hereinbefore). The staring materials of the above-mentioned reaction scheme, namely hydroxyindolealdehyde and hydroxybenzothiophenealdehyde can be prepared, for example by referring the processes disclosed in WO 96/35688, EP 505322. [Synthetic process 4] The compound of the invention wherein R^ ig propyl can be prepared according to the following reaction scheme. ■,1 N-, r^i.- K .^ X'—V—X'- -Z- A COaR Ra Rs Reduction ^ -% x'—Y f? V Z—A—COjR ^■^ R. fls Hydrolysis '^"4_,._,_,. o-^ ^A R* Ps (In the formulas. A, Rl, R^, R-*, R^, X^, YP-. Y, Z and R are those described hereinbefore). The other compounds represented by the formula (I) can also be prepare according to an analogous method- The prepared compounds according to the invention are set forth in Tables 1 to 24. {Typical compounds 1) The compounds of the invention wherein X^ is a bond, Bi is N, B2 is O, R^ is H are shown in Tables 1 to 5 (in which R1 is a substituent at the 2nd position of the imi¬dazole, oxazole or thiazole ring, and R2 is a substituent at the 4th position of the imidazole, oxazole or thiazole ring). CO2H TABLE 1 Rl R2 R3 (po¬sition of sub¬stitu¬tion) R^ R5 A xi Y 2 (po¬sition of substi tu-tion) (4-CF3) Iso- Allyl Me Me S Bond CH2- 0 (6) Phenyl propyl (7) CH2 (4-Cl) Iso- Methyl H H S Bond CH2- 0 (6) Phenyl propyl (7) CH;, (4-t-Bu) Iso- Methyl Me Me 0 Bond CH2- 0 (6) Phenyl propyl (5,7) CH? (3,4-Cl) Iso- Propyl H H S Bond CH2- 0 (6) Phenyl propyl (7) CH2- (3,4-Me) Iso- Butyl Me Et S Bond CH2- S (6) Phenyl propyl (7) CHp (2,4-F} Iso- Hexyl Me H S Bond CH2- 0 (6) Phenyl propyl (7) CH;, (2,3-F) Iso- Isopro- Me Et 0 NHCO CH2- 0 (6) Phenyl propyl pyl (7) CH? (4-OMe) Iso- 2- H H NH Bond CH2- 0 (6) Phenyl propyl Pro-pynyl (7)) CH2 4- Iso- 2- H H NMe Bond CH2- 0 (6) Acetyl- propyl Butenyl CH2 phenyl (7) TABLE 2 Rl R2 R3 (po¬sition of sub¬stitu¬tion) R" R^ A xi Y Z (po¬sition of sub¬stitu¬tion) 4- Iso- 2- Me Me S Bond CH2~ S (6} Cyclo- propyl Pen- CH2 hexyl- tenyl phenyl (7} (4-NO2) Iso- Isobu- H H S Bond CH2- 0 (6) Phenyl propyl tyl (5) CH? {4-NH2) Iso- t-Butyl Me Me 0 Bond CH2- 0 (6) Phenyl propyl (5) CH2 {4-NMe2} Iso- Allyl H H s CONH CH2- 0 (6) Phenyl propyl (5) CH? (3,4,5- Iso- Methyl Me Me s Bond CHj- 0 (6) Me) propyl (5) CH2 Phenyl (3,5-Me, Iso- Methyl Me H s Bond CH2- S (6) 4-OH} propyl (5,7) CH2 Phenyl 3- Iso- Propyl Me Et 0 Bond CH2- 0 (6) Pyridyl propyl (7) CH? 2- Iso- Butyl H H NH CH(0 CH2- 0 (6) Pyridyl propyl (7) H) CH2 3- Iso- Hexyl H H NMe Bond CH2- 0 (6) Pyridyl propyl (7) CH2 TABLE 3 Rl R2 R3 {po¬sition of sub¬stitu¬tion) R^ R5 A xi Y Z {po¬sition of substi tu-tion) 2- Iso- Isopro- Me Me S Bond CH2- 0 (6) Naphthyl propyl pyl (7) CH? 1- Iso- 2- H H S Bond CH2- S (6) Naphthyl propyl Pro- pynyl (7) CH2 2- Iso- 2- Me Me 0 CO CH2- 0 (6) Quinolyl propyl Butenyl {7) CH2 (4-CF3) Propyl 2- H H S Bond CH2- 0 {6) Phenyl Pen-tenyl (7) CH2 (4-Cl) Hexyl Isobu- Me Me S Bond CH2- 0 {6) Phenyl tyl (5) CH2- (4-t-Bu) Butyl t-Butyl Me H S Bond CH2- 0 (6) Phenyl (5) CH^ (3,4-Cl) Isobu- Allyl Me Et 0 Bond CH2- S (6) Phenyl tyl (7) CH;, (3,4-Me) Ethyl Methyl H H NK Bond CH2- 0 (6i Phenyl (7) CH2 (2,4-F) Propyl Methyl H H NMe Bond CH2- 0 (6) Phenyl (5,7) CH2-CH2 TABLE 4 Rl R2 R3 {po¬sition of sub¬stitu¬tion) R^ R5 A xi Y Z (po¬sition of substi tu-tion) (2,3-F) Hexyl Propyl Me Me S Bond CH2- 0 (6) Phenyl (7) CH? (4-OMe) Butyl Butyl H H S Bond CH2- 0 (6) Phenyl (7) CHp 4- Iso- Hexyl Me Me 0 Bond CH2- S (6} Acetyl- butyl (7) CH2 phenyl 4- Ethyl Isopro- H H S Bond CH2- 0 (6) Cyclo- pyi (7) CH2 hexyl- phenyl (4-NO2) Pro- 2- Me Me S Bond CH2- 0 (6) Phenyl pyl Propynyl (7) CH2 (4-NH2) Hexyl 2" Me H S NMe CH2- 0 (6) Phenyl Butenyl (7) CH2 (4-NMe2) Butyl 2- Me Et 0 Bond CHg- 0 (6) Phenyl Pentenyl (7) CH2 (3,4,5- Iso- Isobutyl H H NH Bond CH2- S (6) Me) butyl (5) CH2 Phenyl (3,5-Me, Ethyl t-Butyl H H NMe Bond CH2- 0 (6) 4-OH) (5) CH2- Phenyl CH2 TABLE 5 Rl R2 R3 (po¬sition of sub¬stitu¬tion) R4 R5 A xi Y 2 (po¬sition of sub¬stitu¬tion) (3,4-Cl) Iso- Propyl H H S Bond CH2- 0 (5) Phenyl propyl (4) CHp (3,4-Me} Tri- Butyl Me Me S NH- CHg- S (5) Phenyl flu~ oro-methyl (4) CH2 CH2 (2,4-F) Iso- Hexyl Me H 3 Bond CH2- 0 (5) Phenyl propyl (4) CHp (2,3-F) Iso- Isopro- Me Et 0 Bond CH2- 0 (5) Phenyl propyl pyl (4) CHp (4-OMe) Benzyl 2- H H NH Bond CH2- 0 (5) Phenyl Pro-pynyl (4) CH2 4- Iso- 2- H H NMe Bond CH2~ 0 (5) Acetyl- propyl Butenyl CH2 phenyl (4) 4- Iso- 2- Me Me 3 Bond CH2- S (5) Cyclo- propyl Pen- CH2 hexyl- tenyl phenyl (4) (Typical compounds 2) The compounds of the invention wherein X^ is a bond, B^ is M, B2 ig o, R6 is H are shown in Tables 6 to 10 (in which R^ is a substituent at the 2nd position of the imi¬dazole, oKaEole or thiazole ring, and R^ is a substituent at the 5th position of the imidazole, oxazole or thiazole ring). ■^x TABLE 6 Rl R2 R3 (po¬sition of sub¬stitu¬tion) R^ R5 A xi Y Z (po¬sition of sub¬stitu¬tion) f2,4-Cl} Iso- Allyl H H 0 Bond CH2- 0 (6) Phenyl propyl il) Ctip (2,4-Cl) Iso- Allyl Me Me 0 Bond CH2- 0 (6) Phenyl propyl (7) CH? (2,4-Cl) Iso- Propyl H H 0 Bond CH2- 0 (6) Phenyl propyl (7) CH2 (2-OH, Iso- Propyl H H S CH(0 CH2- 0 (6) 4-Cl) propyl (7) H) CHp Phenyl (3,4-Me) Iso- Methyl Me Me S Bond CH2- S (6) Phenyl propyl (5,7} CH? (2,4-Me) Iso- Hexyl Me H 3 Bond CHg- 0 (6) Phenyl propyl (7) CH2 (2,3-F) Iso- Isopro- Me Et 0 CO CH2- 0 (6) Phenyl propyl pyl (7) CH;; {4-OMe) Iso- 2- H H NH Bond CH2- 0 (6) Phenyl propyl Pro- pynyl (7)) CH2 4-. Iso- 2- H H NMe Bond CH2- 0 (6} Acetyl- propyl Butenyl CH2 phenyl (7) TABLE 7 Rl R2 R3 (po¬sition of sub¬stitu¬tion) R" R5 A xi Y Z (po¬sition of substi tu-tion) 4- Iso- 2- Me Me S NHCO CH2- S (6) Cyclo- propyl Pen- CH2 hexyl- tenyl phenyl (7) (4-NO2) Iso- Isobu- H H S CONH CH2- 0 (6) Phenyl propyl tyl (5) CH2 (4-NH2) Iso- t-Butyl Me Me 0 Bond CH2- 0 (6) Phenyl propyl (5) CH, (4-NMe2) Iso- Allyl H H S Bond CHg- 0 (6) Phenyl propyl (7) CH;> (3,4,5- Iso- Methyl Me Me S CO CH2- 0 (6) Me) propyl (7) CH2- Phenyl CHp (3,5-Me, IsQ- Methyl Me H s Bond CH2- S (6) 4-OH) propyl (5,7) CH2 Phenyl 3- Iso- Propyl Me Et 0 Bond CH2- 0 (6) Pyridyl propyl' (7) CH2 2- Iso- Butyl H H NH Bond CH2- 0 (6) Pyridyl propyl (7) CH2 3- Iso- Hexyl H H NMe Bond CH2- 0 (6) Pyridyl propyl (7) CH2 TABLE 8 Rl R2 R3 (po¬sition of sub¬stitu¬tion) R^ R5 A xi Y Z (po¬sition of sub¬stitu¬tion) 2- Iso- Isopro- Me Me S Bond CH2~ 0 (6) Naphthyl propyl pyl (7) CHp 1- Iso- 2- H H S Bond CH2' S (6) Naphthyl propyl Pro- pynyl (7) CH2 2- Iso- 2- Me Me 0 Bond CH2- 0 (6) Quinolyl propyl Butenyl (7) CH2 (4-CF3) Propyl 2- H H s NH CHj- 0 (6) Phenyl Pen- tenyl (7) CH2-CH2 (4-Cl) Hexyl Isobu- Me Me s Bond CH2- 0 (6) Phenyl tyl (5) CHp (4-t-Bu) Butyl t-Butyl Me H 3 Bond CH2- 0 (6) Phenyl (5) CH2 (3,4-Cl) Isobu- Methyl Me Et 0 Bond CH2- S- (6) Phenyl tyl (5,7) CH2 (3,4-Me) Ethyl Methyl H H NH Bond CH2- 0 (6) Phenyl O) CH^ (2,4-F) Propyl Methyl H H NMe Bond CH2- 0 (6) Phenyl (5,7) CH2 TABLE 9 R^ R2 R3 (po¬sition of sub¬stitu¬tion) R' R5 A xi Y Z (po¬sition of sub¬stitu¬tion) (2,3-F) Hexyl Propyl Me Me 3 CH= CH2- 0 (6) Phenyl H) CH CH;, (4-OMe) Butyl Butyl H H S Bond CH2- 0 (6) Phenyl (7) CRy 4- Iso- Hexyl Me Me 0 NMe CH2- S (6) Acetyl- butyl (7) CH2- phenyl CHp 4- Ethyl Isopro- H H s Bond CH2- 0 (6) Cyclo- pyi (7) CH2 hexyl- phenyl (4-NO2) Pro- 2- Me Me s Bond CH2- 0 (6) Phenyl pyl Propynyl (7) CH2 {4-NH2) Hexyl 2- Me H s Bond CH2- 0 (6) Phenyl Butenyl (7) CH2 (4-NMe2) Butyl 2- Me Et 0 Bond CH2- 0 (6) Phenyl Pentenyl (7) CH2 (3,4,5- Iso- Isobutyl H H NH CH{0 CH2- S (6) Me) butyl (5) H) CH2- Phenyl CH2 (3,5-Me, Ethyl t-Butyl H H NMe Bond CH2- 0 (6) 4-OH) (5) CH2 Phenyl TABLE 10 Rl R2 R3 (po¬sition of sub¬stitu¬tion) R4 R5 A xi Y 2 (po¬sition of substi tu-tion) (2,4-Cl) Iso- Allyl H H 0 Bond CH2- 0 (5) Phenyl propyl (4) CHp (2,4-Cl) Tri- Allyl Me Me 0 Bond CH2- 0 (5) Phenyl flu-oro-methyl (4) CH2 (2,4-Cl) Iso- Propyl H H 0 Bond CH2- 0 (5) Phenyl propyl (4) CH2 (2'OH, Iso- Propyl H H s Bond CH2-' 0 (5) 4-Cl) propyl (4) CH2 Phenyl (3,4-Me) Benzyl Methyl Me Me s Bond CH2- S (5) Phenyl (4) CHj (2,4-Me) Iso- Hexyl Me H s Bond CH2- 0 (5) Phenyl propyl (4) CHp (2,3-F) Iso- Isopro- Me Et 0 Bond CH2- 0 (5) Phenyl propyl pyl (4) CH2 (Typical compounds 3) The compounds of the invention wherein X^ is a bond, R^ is H are shown in Tables 11 to 15 (in which R^ is a substituent at the 2nd position of the imidazole, oxazole or thiazole ring, and R^ is a substituent at the 4th posi¬tion of the imidazole, oxazole or thiazole ring) . 4 X^—Y- ^ 6 CO2H 7^.- 1 In Tables 11 to 15, (*) means the position of substitution. TABLE 11 Rl R2 R3 R^ R5 A Bl B2 xi Y Z (*} (2,4- Iso- Allyl H H 0 CH 0 Bond CH2- 0 Cl) pro- (7) CH2 (6) Phenyl pyl (2,4- Iso- Allyl Me Me 0 CH 0 CO CH2- 0 Cl) pro- (7) CH2 (6) Phenyl pyl (2,4- Iso- Pro- H H 0 CH S Bond CH2- 0 Cl) pro- pyl CH2 (6) Phenyl pyl (7) {2-OH, Iso- Pro- H H S CH NH Bond CH2~ 0 4-Cl) pro- pyl CH2- (6) Phenyl pyl (7) CH2 (3,4- Iso- Me Me Me S N S Bond CH2- 3 Me) pro- (5,7) CH2 (6) Phenyl pyl (2,4- Iso- Hexyl Me H s CH NMe CONH CH2- 0 Me) pro- (7) CH2 (6) Phenyl pyl (2,3- Iso- Iso- Me Et 0 CH NPr Bond CH2- 0 F) pro- pro- CH2 (6) Phenyl pyl pyl (7) (4- Iso- 2- H H NH CH 0 CH(0 CH2' 0 OMe) pro- Pro- H) CH2 (6) Phenyl pyl pynyl (7) 4-Ace- Iso- 2- H H NMe CH 0 Bond CH= 0 tyl- pro- Bu- CH (6) phenyl pyl tenyl (7) TABLE 12 Rl R2 R3 Rl R5 A Bl B2 xi Y Z (*) 4- Iso- 2- Me Me S CH S Bond CH2- s Cyclo- pro- Pen- CH2 (5) hexyl- pyi tenyl phenyl (7) (4- Iso- Iso- H H S CH NH Bond CH2- 0 NO2) pro- butyl CH2 (6) Phenyl pyi (5) (4- Iso- t- Me Me 0 N S NHCO CH2- 0 NH2) pro- Butyl CH2 (6) Phenyl pyl (5) (4- Iso- Allyl H H S CH NMe Bond CH2- 0 NMeg) pro- n) CH2 (6) Phenyl pyl (3,4,5 Iso- Me Me Me S CH t4Pr Bond CH2-- 0 -Me) pro- (7) CH2 (6) Phenyl pyl (3,5- Iso- Me Me H S CH 0 CH{0 CH2- S Me, 4- pro- (5,7) H) CH2- (6) OH) pyl CH2 Phenyl 3- Iso- Pro- Me Et 0 CH 0 Bond CH2- 0 Pyri- pro- pyl CH2 (6) dyl pyi (7) 2- Iso- Butyl H H NH CH S Bond CH2- 0 Pyri- pro- (7) CH2- (6) dyl pyi CH2 3- Iso- Hexyl H H NMe CH NH Bond CH2- 0 Pyri- pro- (7) CH2 (6) dyl pyl TABLE 13 Rl R2 R3 (*) R4 R5 A Bl B2 xi Y Z 2- Iso- Iso- Me Me S N S CONK CH2- 0 Naph- pro- pro- CH2 (6) thyl pyl pyl (7) 1- ISO- 2- H H S CH NMe Bond CH2- S Naph- pro- Pro- CH2 (6) thyl pyl pynyl (7) 2- Iso- 2- Me Me 0 CH NPr Bond CH2- 0 Qui- pro- Bu- CH2 (6) nolyl pyl tenyl (7) (4~ Pro- 2- H H S CH 0 Bond CH2- 0 CF3) pyl Pen- CH2 (6) Phenyl tenyl (7) (4-Cl) Hex- ISQ- Me Me S CH 0 Bond CH2- 0 Phenyl yi butyl (7) CH2 (6) (4-t- Bu- t- Me H S CH s Bond CH2- 0 Bu) tyl Butyl CH2 (6) Phenyl (7) (3,4- Iso- Me Me Et 0 CH NH Bond CHg- S Cl) bu- (5,7) CH2 (6,) Phenyl tyl (3,4- Et Me H H NH N S Bond CH= 0 Me) (7) CH (6) Phenyl (2,4- Pro- Me H H NMe CH NMe Bond CH2- 0 F) pyl (6,7) CH2 (6) Phenyl TABLE 14 Rl R2 R3 R^ R5 A Bl B2 xi Y Z {2,3- Hex- Pro- Me Me S CH NPr Bond CH2- 0 F) yi pyl CH2 (6) Phenyl (7) (4- Bu- Butyl H H S CH 0 Bond CH2- 0 OMe} tyl (7) CH2 (6) Phenyl 4- Iso- Hexyl Me Me 0 CH 0 Bond CH2- S Ace- bu- (7) CH2 (6) tyl- tyl phenyl 4- Et Iso- H H S CH S CH(0 CH2- 0 Cyclo- pro- H) CH2 (6) hexyl- pyl phenyl (7) (4- Pro- 2- Me Me S CH NH Bond CH2- 0 NO2) pyl Pro- CH2 (6) Phenyl pynyl (7) (4- Hex- 2- Me H S N S Bond CH2- 0 NH2) yi Bu- CH2 (6) Phenyl tenyl (7) (4- Bu- 2- Me Et 0 CH NMe Bond CH2- 0 NMe2) tyl Pen- CH2 (6) Phenyl tenyl (7) (3,4,5 Iso- Iso- H H NH CH NPr Bond CH2- S -Me) bu- butyl CH2 (6) Phenyl tyl (7) 1 1 TABLE 15 Rl R2 R3 R^ R5 A Bl B2 xi Y Z (*) (3,5- Et t- H H NMe CH 0 NH CHj- 0 Me, 4- Butyl CH2- (6) OH} (5) CH2 Phenyl (2,4- Iso- Allyl H H 0 CH 0 Bond CH2- 0 CI} pro- (5) CH2 (6} Phenyl pyl (2,4- Tri- Allyl Me Me 0 CH s NMe CH2- 0 Cl) flu- (5) CH2- (6) Phenyl oro-eth- CH2 (2,4- Ben- Pro- H H 0 CH NH Boned CH2- 0 Cl) zyl pyl CH2 (6) Phenyl (5) (2-OH, Iso- Pro- H H S N S Bond CH2' 0 4-Cl) pro- pyl CH2 (6) Phenyl pyl (5) (3,4- Iso- Me Me Me S CH NMe Bond CH2" S Me) pro- (5) CH2 (6) Phenyl pyl (2,4- Iso- HexyL Me H S CH NPr Bond CH2' 0 Me) pro- (5) CH2 (6) Phenyl pyl (2,3- Iso- Isopr Me Et 0 CH 0 Bond CH2' 0 F) pro- opyl CH2 (6) Phenyl pyl (5) (Typical compounds 4) The compounds of the invention wherein X^ is a bond, R^ is H are shown in Tables 16 to 20 (in which R^ is a substituent at the 2nd position of the imidazole, oxazole or thiazole ring, and R^ is a substituent at the 5th posi¬tion of the imidazole, oxazole or thiazole ring). X'—y In Tables 16 to 20, (*) means the position of sub¬stitution. TABLE 16 Rl R2 R3 (*) Ri R5 A El B2 xi Y Z (*) {4- Iso- Allyl Me Me S CH 0 Bond CH2- 0 CF3) pro- iV CH2 (6) Phenyl pyi (4-Cl) Iso- Me H H S CH 0 Bond CH2- 0 Phenyl' pro-pyl (7) CH2 (6) {4-t- Iso- Me Me Me 0 CH s CH{0 CH2- 0 Bu) pro- (5,7) H) CH2 (6) Phenyl pyl {3,4- Iso- Pro- H H s CH NH Bond CH2- 0 CI} pro- pyl CH2- (6) Phenyl pyl (7) CH^ (3,4- Iso- Butyl Me Et s N S Bond CH= S Me) pro- C7) CH (6) Phenyl pyl (2,4- Iso- Hexyl Me H s CH NMe Bond CH2- 0 F) pro- (7) CH2 (6) Phenyl pyl (2,3- Iso- Iso- Me Et 0 CH NPr CO CH2- 0 F) pro- pro- CH2 (6) Phenyl pyl pyl (7) (4- Iso- 2- H H WH CH 0 Bond CH2- 0 OMe) pro- Pro- CH2 (6) Phenyl pyl pynyl (7) 4-Ace- Iso- 2- H H NMe CH 0 Bond CH2- 0 tyl- pro- Bu- CH2 (6} phenyl pyi tenyl (7) TABLE 17 Rl R2 R3 R^ R5 A Bl B2 xi Y Z (*) 4- Iso- 2- Me Me S CH S Bond CH2- s Cyclo- pro- Pen- CH2 (6) hexyl- pyl tenyl phenyl (7) (4- Iso- Iso- H H S CH NH CONH CHg- 0 NO2) pro- butyl CH2 (5) Phenyl pyl (5} (4- Iso- t- Me Me 0 N S Bond CH2- 0 NH2) pro- Butyl CH2 (6) Phenyl pyi (5) (4- Iso- Allyl H H S CH NMe Bond CH2- 0 NMe2) pro- (7) CH2 (6) Phenyl pyl (3,4,5 Iso- Me Me Me S CH NPr Bond CH2- 0 -Me) pro- (7) CH2 (6) Phenyl pyl (3,5- Iso- Me Me H S CH 0 CO CH2- S Me, 4- pro- (5,7) CH2- (6) OH) pyl CH2 Phenyl 3- Iso- Pro- Me Et 0 CH 0 Bond CH2- 0 Pyri- pro- pyl CH2 (6) dyl pyl (7) 2- Iso- Butyl H H NH CH S CO CH= 0 Pyri- pro- (7) CH- (6) dyl pyl CH2- CH2 3- Iso- Hexyl H H NMe CH NH Bond CH2- 0 Pyri- pro- (7) CH2 (6) dyl pyl TABLE 18 Ri R2 R3 R4 R5 A Bl B2 xi Y Z (*) 2- Iso- Iso- Me Me S N S Bond CH2- 0 Naph- pro- pro- CH2 (6) thyl pyl pyl (7) 1- Iso- 2- H H S CH NMe NMe CH2- S Naph- pro- Pro- CH2- (6) thyl pyl pynyl [1] CH2 2- Iso- 2- Me Me 0 CH NPr Bond CH2- 0 Qui- pro- Bu- CH2 (6) nolyl pyl tenyl (7} (4- Pro- 2- H H 3 CH ^0 Bond CH2- 0 CF3) pyl Pen- CH2 (6) Phenyl tenyl (7) (4-Cl) Hex- Iso- Me Me S CH 0 Bond CH2- 0 Phenyl yi butyl (7} CH2 (6} (4-t- Bu- t- Me H S CH s NMe CH2- 0 Bu) tyl Butyl CH2- (6) Phenyl (7) CH2 (3,4- Iso- Allyl Me Et 0 CH NH Bond CH2- S Ci) bu- (7) CH2 (6) Phenyl tyl (3,4- Et Me H H NH N S Bond CH2- 0 Me) (7) CH2 (6) Phenyl {2,4- Pro- Me H H NMe CH NMe Bond CH2- 0 F) pyl (6,7) CH2 (6) Phenyl TABLE 19 Rl R2 R3 (*) R" R5 A Bl B2 xi y 2 (*) (2,3- Hex- Pro- Me Me S CH NPr Bond CH2- 0 F) yi pyl CH2 (6) Phenyl (7) (4- Bu- Butyl H H S CH 0 Bond CH2- 0 OMe) tyl (7) CH2 (6) Phenyl 4- Iso- Hexyl Me Me 0 CH 0 Bond CH2- S Ace- bu- (7) CH2 (6) tyl- tyl phenyl 4- Et Iso- H H S CH s Bond CH2- 0 Cyclo- pro- CH2 (6) hexyl- pyl phenyl (7) (4- Pro- 2- Me Me S CH NH Bond CH2- 0 NO2) pyl Pro- CH2 (6) Phenyl pynyl (7) (4- Hex- 2- Me H S N S CH(0 CH2- 0 NH2) yi Bu- H) CH2- (6) Phenyl tenyl (7) CH2 (4- Bu- 2- Me Et 0 CH NMe Bond CH2- 0 NMe2) tyl Pen- CH2 (6) Phenyl tenyl (7) (3,4,5 Iso- Iso- H H NH CH NPr Bond CH2- S -iyie) bu- butyl CH2 (6) Phenyl tyl (5} TABLE 20 Ri R2 R3 (*) R^ R5 A Bl B2 xi Y Z (*) (3,5- Et t- H H NMe CH 0 Bond CH2- 0 Me, 4- Butyl CH2 (6) OH) (5) Phenyl (3,4- ISD- Pro- H H S CH 0 Bond CH2- 0 CI) pro- pyl CH2 (6) Phenyl pyl (5) (3,4- Tri- Butyl Me Me S CH s Bond CH2- S Me} flu- (5) CH2 (6) Phenyl oro-meth yi (2,4- Ben- Hexyl Me H S CH NH Bond CH2- 0 F} zyl (5) CH2 (6) Phenyl (2,3- Iso- Isopr Me Et 0 N S Bond CH= 0 F) pro- opyl CH (6) Phenyl pyl (5) (4- Iso- 2- H H NH CH NMe Bond CH2- 0 OMe) pro- Pro- CH2 (6) Phenyl pyl pynyl (5) 4-Ace- Iso- 2- H H NMe CH NPr Bond CH2- 0 tyl- pro- Bu- CH2 (5) phenyl pyl tenyl (4) 4- ISD- 2- Me Me S CH 0 Bond CH2- S Cyclo- pro- Pen- CH2 (5) hexyl- pyl tenyl phenyl (4) (Typical compounds 5) The compounds of the formula (I) wherein A is S, X^ is a bond, X^ is a bond, Y is CH2CH2, E^ is M, B^ is O, R^ is a substituent at the 2nd position, R^ is a substituent at the 4th position (namely Y is attached to the 5th po¬sition) are shown in Tables 21 and 22. TABLE 21 Rl R2 R^ (posi¬tion of substitu¬tion) Rl R5 Z (posi¬tion of substi¬tution) (4-CF3)Phenyl Isopropyl Methyl (5) H H 0 (6) (4~CF^) Phenyl Isopropyl Methyl (5) Me Me 0 (6) (4-CF^) Phenyl Isopropyl Methyl (5) H H S (6) (4-CF^)Phenyl Isopropyl Methyl (5) H H NH (6) (4-OCFT)Phenyl Isopropyl Methyl (5) H H 0 (6) (4-OCF-;,} Phenyl Isopropyl Methyl (5) Me Me 0 (6) (4-Cl)Phenyl Isopropyl Methyl (5) H H 0 (6) (4-Cl)Phenyl Isopropyl Methyl (5) Me Me 0 (6) (4-CF3) Phenyl Isopropyl CI (5) H H S (6) (4-CF-^) Phenyl Isopropyl CI (5) Me Me 0 (6) (4-CFn) Phenyl Isopropyl F (5) H H S (6) (4-CF3)Phenyl Isopropyl F (5) Me Me 0 (6) (4-CF^) Phenyl Isopropyl Allyl (5) H H 0 (6) (4-CF3) Phenyl Isopropyl Allyl {5} Me Me 0 (6) (4-CF^}Phenyl Isopropyl Ethyl (5) H H 0 (6) (4'CFtt) Phenyl Isopropyl Ethyl (5) Me Me S (6) TABLE 22 Rl R2 R3 (posi¬tion of substitu¬tion} R^ R5 Z (posi¬tion of substi¬tution) 4-Pyridyl Isopropyl Methyl (5) H H 0 (6) 4--Pyridyl Isopropyl Methyl (5) Me Me 0 (6) (4-Me)Phenyl Isopropyl Methyl (5) H H S (6) (4-Me)Phenyl Isopropyl Methyl (5) Me Me 0 (6) (4-Me)Phenyl Hexyl Methyl (5) H H 0 (6) (4-Me)Phenyl Hexyl Methyl (5) Me Me 0 (6) (4-CF^)Phenyl Hexyl Methyl (5) H H 3 (6) (4-CF^)Phenyl Hexyl Methyl (5) Me Me 0 (6) (4-CF3)Phenyl (4-CF3} Phenethyl Methyl (5) H H S (6) (4-CF3) Phenyl (4-CF3) Phenethyl Methyl (5) Me Me 0 (6) (4-CF3) Phenyl Sec-butyl Methyl (5) H H 0 (6) (4-CF3) Phenyl Sec-butyl Methyl (5) Me Me 0 (6) (4-CF3) Phenyl Butyl Methyl (5) H H 0 (6) (4-CF3)Phenyl Butyl Methyl (5) Me Me 0 (6) (4-CF3) Phenyl Ethyl Methyl (5) H H 0 (6) (4-CF3) Phenyl Methyl Methyl (5} Me Me 0 (6) (Typical compounds 6) The compounds of the formula (I) wherein A is O, R2 is isopropyl, X^ is a bond, X^ is a bond, Y is CH2CH2, B^ is N, B2 is O, R^ is a substituent at the 2nd position, R^ is a substituent at the 5th position (namely Y is at¬tached to the 4th position) are shown in Table 23. TABLE 23 Rl R3 (position of substitution) R^ R5 Z (position of substitution) (2,4-Cl)Phenyl Methyl (5) H H 0 (5) {2,4-Cl)Phenyl Methyl (5) Me Me 0 (6) (2,4-Cl)Phenyl Methyl (5) H H S {6) (4-CF3) Phenyl Methyl (5) H H NH (6) (4-0CF-;i) Phenyl Methyl (5) H H 0 (6) (4-OCF3)Phenyl Methyl (5) Me Me 0 (6) (4-CF3) Phenyl CI (5) H H S (6) (4-CF3) Phenyl CI (5) Me Me 0 (6) (4-CF3) Phenyl F (5) H H S (6) (4-CF-,) Phenyl F (5) Me Me 0 (6) (4-CF3) Phenyl Allyl (5} H H 0 (6) (4-CF^) Phenyl Allyl (5) Me Me 0 (6) (4-CF-,) Phenyl Ethyl (5) H H 0 (6) (4-CF^)Phenyl Ethyl (5) Me Me S (6) (Typical compounds "7) The compounds of the formula (I) wherein R^ is methyl, which is a substituent at the 5th position, X^ is a bond, X^ is a bond, Y is CH2CH2, B^ is N, B2 is 0, Ri is a substituent at the 2nd position, R^ is a substituent at the 5th position (namely Y is attached to the 4th posi¬tion) are shown in Table 24. TABLE 24 Rl R2 R^ R5 A Z (posi¬tion of sub-sti-tu- 4-Pyridyl Isopropyl H H 0 ©ifffi) 4-Pyridyl Isopropyl Me Me 0 0 (6} (4-Me)Phenyl Isopropyl H H 0 S (6) (4-Me)Phenyl Isopropyl Me Me 0 0 (6) £4-Me)Phenyl Bexyl H H 0 0 (6) (4-Me)Phenyl Hexyl Me Me 0 0 (6) (4-CF^)Phenyl Hexyl H H 0 S (6) (4-CF^) Phenyl Hexyl Me Me 0 0 (6) (4-CF3) Phenyl (4-CF.,) Phenethyl H H NH S (6) (4-CF-,) Phenyl (4-CF^)Phenethyl Me Me NMe 0 (6) {2-OH,4-Cl) Phenyl Isopropyl H H 0 0 (6) (2-OH,4-Cl) Phenyl Isopropyl Me Me 0 0 (6) The pharmacological effects of the invention are de¬scribed below. PPAR5 transactivation activity of the compound of the invention was measured in the manner described below. A receptor expression plasmid {GAL4-hPPAR5 LBD), a reporter plasmid (UASx4-TK-LUC) and a p-galactosidase (p-GAL) expression plasmid were transfeeted into CV-1 cells by using DMRIE-C reagent. Subsequently, the cells were incubated for 40 hours in the presence of a compound of the invention, and then the luciferase and p-GAL activi¬ties of the cell lysate were assayed. The luciferase activity was corrected by the p-GAL activity, and a relative transactivation activity was calculated under the condition that the luciferase activ¬ity of the cells treated by L-165041 was regarded as 100% (see the below-mentioned Examples 11 and 12). As shown in Tables 25 and 26, it is clear that the compounds of the invention (Examples 1, 2, 5-10) show se¬lective and potent PPAR5 transactivation activities. Furthermore, it is clear from Table 27 the compound described in Example 6 show a potent HDL cholesterol ele¬vating effect. Apparently, the compounds of the invention having the general formula (I) show potent PPAR5 transactivation activities. Accordingly, these compounds are expected to be useful for prevention and treatment of the following diseases: hyperglycemia, diabetes, insulin resistance, dyslipidemia, hyperlipidemia, obesity, syndrome X, hyper¬cholesterolemia, other dyslipidemia such as hyperlipo-preoteinemia, atherosclerosis, diseases of cardiovascular systems, hyperphagia, ischemic diseases, malignant tumors such as lung cancer, mammary cancer, colonic cancer, can¬cer of great intestine, and ovary cancer, Alzheimer's disease, inflammatory disease, osteoporosis (Mano H. et al., (2000) J. Biol. Chem., 175:8126-8132), Basedow's disease, and adrenal cortical dystrophy. The compound of the invention can be administered to human by ordinary administration methods such as oral ad¬ministration or parenteral administration. The compound can be granulated in ordinary manners for the preparation of pharmaceuticals. For instance, the compound can be processed to give pellets, granule, pow¬der, capsule, suspension, injection, suppository, and the like. For the preparation of these pharmaceuticals, ordi¬nary additives such as vehicles, disintegrators, binders, lubricants, dyes, and diluents. As the vehicles, lactose, D-mannitol, crystalline cellulose and glucose can be men¬tioned. Further, there can be mentioned starch and car-boxymethylcellulose calcium (CMC-Ca) as the disintegra¬tors, magnesium stearate and talc as the lubricants, and hydroxypropylcellulose (HPC) , gelatin and polyvinyl¬pyrrolidone (PVP) as the binders. The compound of the invention can be administered to an adult generally in an amount of 0.1 mg to 100 mg a day by parenteral administration and 1 mg to 2,000 mg a day by oral administration. The dosage can be adjusted in consideration of age and conditions of the patient. The invention is further described by the following non-limiting examples. [Examples] (Example 1) [[7-Allyl-3-[2-[2-(2,4-dichlorophenyl)-5~isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxa20l-6-yl3 oxy] acetic acid (1) 6-Acetamido-3-[2-[2-{2,4-dichlorophenyl)-5-isopropyl—4-oxazolylJethyl]-1,2-benzisoxazole 6-Acetamido-3-methyl-l,2-benzisoxa2ole (571 mg, 3.00 mmol) was dissolved in dry THF (18 mL). 2M of LDA (3.1 mL, 6.2 mmol) was dropwise added to the solution for 10 minutes under nitrogen atmosphere at -78°C. A solution of 4-iodomethyl-5-isoprDpyl-2~(2,4-dichlorophenyl)oxazole (1.19 g, 3.00 mmol) in THF (3.0 mL) was dropwise added to the resulting mixture for 7 minutes. The mixture was stirred for 1 hour under the same conditions. The mixture was allowed to room temperature. A saturated aqueous am¬monium chloride solution and ethyl acetate were added to the mixture. The organic layer was washed with water and saline, and dried over anhydrous sodium sulfate. Ethyl acetate was removed under reduced pressure. The residue was purified by column chromatography on silica gel with chloroform/methanol (80/1) to give the desired compound (904 mg) as pale yellow oil (yield 70%). J-H-NMR (CDCI3 , 400MHz) 5: 1.10 {d, 6H, J=7Hz), 2.22 (s, 3H), 2.93 {dq, IH, J=7Hz, 7Hz), 3.06 (t, 2H, J=7H2), 3.34 (t, 2H, J=7Hz), 7.12 (dd, IH, J=2,9Hz), 7.32 (dd, IH, J=2^9Hz), 7.37 (d, IH, J=2Hz), 7.43 (d, IH, J=9H2), 7.51 (d, IH, J=2Hz), 7.89 (d, IH, J-9Hz), 8.05 (s, IH). (2) 6-Hydroxy-3-[2-[2-(2,4-dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxazole The obtained 6-acetamido-3-[2-[2-(2,4-dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxazole (900 mg, 1.96 mmol) was reacted in 3N hy¬drochloric acid (45 mL) at 100°C for 4 hours. The reac¬tion mixture was allowed to room temperature, neutralized with a saturated aqueous sodium hydrogen carbonate solu¬tion, and extracted with ethyl acetate. The organic layer was washed with saline, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give 6-amino-3-[2-[2-(2,4-dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxa2ole (770 rag) as brown oil in the residue. The product (770 mg, 1.85 mmol) was sus¬pended in 25% sulfuric acid (9.3 mL), and cooled with ice. An aqueous sodium nitrite solution (166 mg, 2.41 mmol/1.3ml} was dropwise added to the suspension for 5 minutes. The resulting solution was stirred for 45 min¬utes under the same conditions. The reaction mixture was dropwise added to a 75% sulfuric acid (7.4 mL) while re-fluxing for 5 minutes, and the mixture was refluxed for 4 hours. The reaction mixture was left to get cool, ex¬tracted with diethyl ether, washed with a saturated aque¬ous ammonium chloride solution and saline, and dried over anhydrous sodium sulfate. Diethyl ether was removed under reduced pressure. The residue was purified by column chromatography on silica gel with hexane/ethyl acetate (3/1) to give the desired compound (138 mg) as pale yel¬low oil (yield of the two steps 17%). iR-NMR (CDCI3, 400MHz} 6: 1.23 (d, 6H, J=7Hz), 2.93 (dq, IH, J=7Hz, IHz), 3.06 {t, 2H, J=7Hz), 3.32 (t, 2H, J=7Hz), 5.36 (s, IH), 6.75 (dd, IH, J=2,8Hz) 6.92 (d, IH, J=2Hz) 7.30 (dd, IH, J=2,8Hz}, 7.35 (d, IH, J=8Hz), 7.51 (d, IH, J=2Hz), 7.89 (d, IH, J=8Hz). (3) 6-Allyloxy-3-[2-[2-(2,4-dichlorophenyl)-5-isopropyl-4~oxazGlyl]ethyl]-1,2-benzisoxazole The obtained 6-hydroxy-3-[2-[2-(2,4-dichlorophenyl}-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxazole {500 mg, 1.20 mmol) and potassium carbonate (249 mg, 1.80 mmol) were suspended in acetone (30 mL) . Allyl bromide (217 mg, 1.80 mmol) was dropwise added to the suspension for 1 minute while cooling with ice. The mixture was allowed to room temperature, and stirred for 20 hours. After insolu- ble was filtered off, the filter cake was washed with acetone. The filtrate and washings were combined, and concentrated. The residue was purified by column chroma¬tography on silica gel with hexane/ethyl acetate (4/1) to give the desired compound (420 mg) as colorless oil (yield 77%). iR-NMR (CDCI3, 400MHz) 5: 1.11 (d, 6H, J=7Hz), 2.92 (dq, IH, J=7H2, 7Hz), 3.06 (t, 2H, J=7Hz), 3.32 (t, 2H, J=7H2), 4.5-4.6 (m, 2H) , 5.3-5.5 (m, 2H) , 6.0-6.1 (m, IH) , 6.86 (dd, IH, J=2,8Hz) 6.96 (d, IH, J=2Hz) 7.32 (dd, IH, J=2,8Hz), 7.36 (d, IH, J=8Hz), 7.51 (d, IH, J=2Hz), 7.90 (d, IH, J=8Hz). (4) 7-Allyl-6-hydroxy-3-[2-[2-(2,4-dichlorophenyl}-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxazole 6-Allyloxy-3-[2-[2-(2,4-dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxazole (70 mg, 0.153 mmol) was heated at 180'C for 4 hours. The product was allowed to room temperature, and purified by column chromatogra¬phy on silica gel with hexane/ethyl acetate (3/1) to give the desired compound (47 mg) as white powder (yield 67%). ^H-NMR (CDCI3, 400MHz) 5: 1.11 (d, 6H, J=7Hz), 2.92 (dq, IH, J=7HE, 7Hz}, 3.05 (t, 2H, J=7Hz), 3.31 (t, 2H, J-7HZ), 3.65-3.70 (m, 2H), 5.15-5.25 (m, 2H}, 5.41 (s, IH), 6.0-6.1 [m, IH}, 6.76 (d, IH, J=8Hz), 7.25 (d, IH, J=8Hz) 7.32 (dd, IH, J=2,8Hz), 7.51 (d, IH, J=2Hz), 7.89 (d, IH, J=8Hz). (5) Ethyl [[7-allyl-3~[2-[2-(2,4-dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxazol-6-yl]oxy]acetate The obtained 7-allyl-6-hydroxy-3-[2-[2-(2,4-dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxazole (45 mg, 0.098 mmol) and potassium carbonate (20 mg, 0.147 mmol) was suspended in acetone (5.0 mL). An acetone solution of ethyl bromoacetate (25 mg, 0.147 mmol) was added to the suspension while cooling with ice. The mixture was allowed to room temperature, and stirred for 20 hours. After insoluble was filtered off, the fil¬ter cake was washed with acetone. The filtrate and wash¬ings were combined, and concentrated. The residue was pu¬rified by column chromatography on silica gel with hex-ane/ethyl acetate (4/1) to give the desired compound (43 mg) as colorless oil (yield 80%). ^H-NMR (CDCI3, 400MHz) 5: 1.11 (d, 6H, J=7Hz), 1.28 (t, 3H, J=7Hz), 2.91 (dq, IH, J=7Hz, 7Hz) , 3.05 (t, 2H, J=7Hz), 3.32 (t, 2H, J=7Hz), 3.65-3.70 (m, 2H) , 4.25 (q, 2H, J=7Hz) 4.70 (3, 2H) 4.95-5.15 (m, 2H) , 6.0-6.1 (m, IH}, 6.74 {d, IH, J=9Hz), 7.30 (d, IH, J-9H2) 7.32 {dd, IH, J=2,9Hz), 7.51 (d, IH, J=2Hz), 7.89 (d, IH, J=9Hz). (6} [[7-Allyl-3-[2-[2-(2,4-dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxazol-6-yl]oxy]acetic acid The obtained ester compound (40 mg, 0.074 mmol) was dissolved in an ethanol-water (3.0 mL-1.5 mL}. Lithium hydroxide Monohydrate of (8 mg) was added to the solu¬tion, and the mixture was stirred for 20 hours. Ice was added to the reaction mixture. The mixture was neutral¬ized with 3N hydrochloric acid. The crystals were fil¬tered, washed with water, air-dried over night, and fur¬ther dried under reduced pressure to give the desired compound (25 mg) as white powder (yield 66%). mp 80-85°C iH-NMR (CDCI3, 400MHz) 6: 1.13 (d, 6H, J=7Hz), 2.94 (dq, IH, J=7Hz, 7Hz) , 3.06 (t, 2H, J=7Hz), 3.31 {t, 2H, J=7Hz), 3.65-3.75 (m, 2H) , 4.73 (s, 2H) 5.0-5.2 (m, 2H), 5.9-6.1 (m, IH), 6.76 (d, IH, J=9Hz), 7.31 (d, IH, J=9Hz) 7.32 (dd, IH, J=2,9Hz), 7.51 (d, IH, J=2Hz), 7.89 (d, IH, J=9Hz). {Example 2) 2-[[7-Allyl-3-[2-[2-(2,4-dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxazQl-6-yl]oxy]-2-methylpropionic acid (1} Ethyl 2-[[7-allyl-3-[2-[2-(2,4-dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxazol-6-yl]oxy]-2-methylpropionate 7-Allyl-6-hydroxy-3-(2-[2-(2,4-dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxazale (92 mg, 0.20 mmol), ethyl 2-bromo-2-methylpropionate (196 mg, 1.00 mmol) and potassium carbonate (138 mg, 1.00 mmol) were suspended in methyl ethyl ketone (5.0 mL) . The sus¬pension was refluxed for 20 hours, and allowed to room temperature. After insoluble was filtered off, the filter cake was washed with methyl ethyl ketone. The filtrate and washings were combined, and concentrated. The residue was purified by column chromatography on silica gel with hexane/ethyl acetate (5/1) to give the desired compound (100 mg) as colorless oil (quantitative yield). ^H-NMR (CDCI3, 400MHz) 5: 1.09 (d, 6H, J=7Hz), 1.23 (t, 3H, J=7Hz), 1.60 (s, 6H), 2.90 (dq, IH, J=7Hz, 7Hz) , 3.04 (t, 2H, J=7Hz), 3.31 (t, 2H, J-7Hz), 3.65-3.70 (m, 2H) , 4.23 (q, 2H, J=7Hz) , 4.95-5.15 (m, 2H) , 6.0-6.1 (m, IH) , 6.65 (d, IH, J=9Hz), 7.19 (d, IH, J=9H2), 7.31 (dd, IH, J-2,9Hz), 7.51 (d, IH, J=2Hz), 7.89 (d, IH, J=9Hz). (2) 2-[[7-Allyl-3-[2-[2-(2,4-dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-1,2-ben2isoxa2ol-6-yl]oxy]-2-methylpropionic acid The desired compound was obtained in an analogous manner as in (6) of Example 1 (yield 73%). iH-NMR (CDCI3, 400MHz) 5: 1.10 (d, 6H, J=7Hz), 1.63 (s, 6H), 2.92 (dq, IH, J=7Hz, 7Hz), 3.06 (t, 2H, J=7Hz), 3.31 (t, 2H, J=7Hz), 3.65-3.70 (m, 2H), 5.00-5.15 (m, 2H), 5.9-6.1 (in, IH) , 6.80 (d, IH, J=8Hz}, 7.21 (d, IH, J=8Hz), 7.30 (dd, IH, J=2,8Hz), 7.49 (d, IH, J=2Hz), 7.85 (d, IH, J=8Hz). (Example 3) [[7-Propyl-3-[2-[2-(2,4~dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxazol-6-yl]oxy]acetic acid (1} Ethyl [[7-propyl-3-[2-[2-(2,4-dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxazol-6-yl]oxy]acetate Ethyl [[7-allyl-3-[2-[2-(2,4-dlchlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxazol-6-yl]oxy]acetate (65 mg, 0.12 mmol) was dissolved in etha-nol (7.0 mL) . To the solution, 10% Pd-C (6mg) was added. The mixture was stirred for 3 hours under hydrogen atmos¬phere (and ordinary pressure). After insoluble was fil¬tered off, the filtrate was condensed to give the desired compound (63 mg) as colorless oil in the residue (yield 97%} . IH-NMR (CDCI3, 400MHz) 5: 0.97 (t, 3H, J=7Hz), 1.09 (d, 6H, J=7Hz), 1.26 (t, 3H, J=7Hz), 1.7-l.S (m, 2H}, 2.9-3.0 (m, 3H), 3.05 (t, 2H, J=7Hz), 3.32 (t, 2H, J=7Hz), 4.25 (q, 2H, J=7Hz), 4.70 (s, 2H}, 6.70 {d, IH, J=8Hz), 7.25 (d, IH, J=9Hz}, 7.33 (dd, IH, J=2,9Hz), 7.51 (d, IH, J=2Hz), 7.89 (d, IH, J=8Hz). (2) [[7-Propyl-3-[2-[2-(2,4-dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxazol-6~yl]oxy]acetic acid The desired compound was obtained in an analogous manner as in (6) of Example 1. iH-NMR (CDCI3, 400MHz) 5: 0.96 (t, 3H, J=7Hz), 1.12 (d, 6H, J=7Hz), 1.7-1.8 (m, 2H}, 2.9-3.0 (m, 3H), 3.06 (t, 2H, J=7Hz), 3.30 (t, 2H, J=7Hz), 4.25 (q, 2H, J=7Hz), 4.74 (s, 2H), 6.74 (d, IH, J=8Hz}, 7.26 (d, IH, J=9Hz), 7.33 (dd, IH, J=2,9Hz), 7.51 (d, IH, J=2Hz), 7.87 (d, IH, J=8Hz). {Example 4) 2-[[7-Allyl-3-[2-[2-[(4-trifluoromethyl)phenyl]-4-isopropyl-5-thiazolyl]ethyl]-1,2-benzisoxazol-6-yl]oxy]-2-methylpropionic acid The following (1) to (5) were conducted in an analo¬gous manner as in Example 1, and the following (6) and (7) were conducted in an analogous manner as in Exainple 2. (1) 6-Acetamido-3-[2-[2-[(4-trifluoromethyl)phenyl]-4- isoprapyl-5-thiazolyl]ethyl]-1,2-benzisoxazole Pale yellow oil Yield 20% iH-NMR (CDCI3, 400MHz} 5: 1.24 (d, 6H, J=7Hz) , 2.23 (3, 3H), 3.03 {dq, IH, J=7Hz, 7Hz), 3.25-3.40 (m, 4H), 7.20 (dd, IH, J=2,9Hz), 7.36 (d, IH, J=2Hz), 7.44 (d, IH, J=9Hz), 7.65 (d, 2H, J=8Hz), 7.99 {d, 2H, J=8Hz), 8.07 (s, IH). (2) 6-Amino-3-[2-[2-[(4-trifluoromethyl)phenyl]-4- isopropyl-5-thiazolyl]ethyl]-1,2~benzisoxazole Pale yellow oil Yield 93% IR-NMR {CDCI3, 400MHz} 6: 1.25 (d, 6H, J=7Hz), 3.04 {dq, IH, J=7Hz, 7Hz) , 3.15-3.40 (m, 4H) , 4.0-4.05 (br, 2H) , 6.61 (dd, IH, J=2,9Hz), 6.73 {d, IH, J=2H2) , 7.27 (d, IH, J=9Hz), 7.65 {d, 2H, J=8Hz}, 8.00 (d, 2H, J=SH2), (3) 6-Hydroxy-3-[2-[2-[(4-trifluoromethyl}phenyl]-4- isopropyl-5-thiazolyl]ethyl]-1, 2-benzisoxa2ole Pale yellow oil Yield 32% iH-NMR (CDCI3, 400MHz) 5: 1.24 {d, 6H, J=7Hz), 3.03 {dq, IH, J=7H2, 7Hz), 3.2-3.4 (m, 4H), 5,95-6.00 (br, IH), 6.83 (dd, IH, J=2,9Hz), 6.79 (d, IH, J=2Hz), 7.38 (d, IH, J=9H2), 7.64 (d, 2H, J=8Hz), 7.99 (d, 2H, J=8Hz). (4) 6-AllylQxy-3-[2-[2-[(4-trifluoromethyl)phenyl]-4- isopropyl-5-thiazolyl]ethyl]-1,2-benzisoxazole Pale yellow oil Yield 49% iH-NMR {CDCI3, 400MHz) 5: 1.24 (d, 6H, J=7Hz), 3.04 (dq, IH, J=7Hz, 7Hz), 3.2-3.4 (m, 4H), 4.60-4.65 (m, 2H), 5.30-5.50 (m, 2H), 6.00-6.15 (ra, IH), 6.93 (dd, IH, J=2,9H2), 7.00 (d, IH, J-2HZ), 7.40 (d, IH, J=9Hz), 7.65 (d, 2H, J=8Hz), 8.00 (d, 2H, J=8Hz). (5} 7-Allyloxy-6-hydroxy-3-[2-[2-[(4- trifluororaethyl}phenyl]-4-isopropyl-5-thiazolyl]ethyl] 1,2-benzisoxazole White powder Yield 71% iH-NMR (CDCI3, 400MHz} 5: 1.24 (d, 6H, J=7Hz), 3.03 (dq, IH, J=7Hz, 7Hz}, 3.2-3.4 (m, 4H}, 3.65-3.75 (m, 2H), 5.15-5.30 (m, 2H), 5.56 (s, IH), 6.00-6.10 {ra, IH), 6.84 (d, IH, J=9Hz), 7.28 (d, IH, J=9Hz), 7.65 (d, 2H, J=8Hz), 8.00 (d, 2H, J=8Hz). {6) Ethyl 2-[I7-allyl-3"[2-[2-[(4- trifluoromethyl)phenyl]-4-isopropyl-5-thiazolyl]ethyl]- 1,2-benzisoxazol-6-yl]oxy]-2-methylpropionate Pale yellow oil Yield 48% iH-NMR (CDCI3, 400MHz) S: 1.23 (t, 3H, J=7Hz), 1.23 (d, 6H, J=7Hz), 1.62 {s, 6H}, 3.02 (dq, IH, J=7Hz, 7Hz) , 3.2-3.4 (m, 4H), 3.65-3.75 (m, 2H) , 4.23 (q, 2H, J=7Hz), 5.0-5.15 (m, 2H), 5.95-6.10 (m, IH) , 6.71 (d, IH, J=9Hz), 7.22 (d, IH, J=9Hz), 7.65 (d, 2H, J-8H2), 7.99 (d, 2H, J=8Hz). (7) 2- [ [7-Allyl-3- [2- [2- [ {4-trifluoroniethyl) phenyl] -4- isopropyl-5-thiazolyl]ethyl]-1,2-benzisoxazol-6-yl]oxy]- 2-methylpropionic acid Colorless oil Yield 81% iH-NMR (CDCI3, 400MHz) 5: 1.23 (d, 6H, J=7Hz), 1.65 (s, 6H), 3.01 (dq, IH, J=7Hz, 7Hz) , 3.2-3.4 {m, 4H), 3.65-3.75 (in, 2H) , 5.0-5.15 (m, 2H), 5.95-6.10 (m, IH}, 6.85 (d, IB, J=9Hz), 7.27 (d, IH, J=9Hz), 7.65 {d, 2H, J=8Hz), 7.99 (d, 2H, J=8Hz). (Example 5) [3-[2-[4-Isopropyl-2-(4-trifluoromethyl)phenyl-5-thiazolyl]-ethyl]-5-methyl-l,2-benzisoxazol-6-yl]oxyacetic acid (1) 6-Acetamido-3-[2-[4-isopropyl-2-(4- trif luoromethyl}phenyl-5-thiazolyl] ethyl] -5-itiethyl-l, 2- benzisoxazole 6-'Acetamido-3, 5-dimethyl-l, 2-benzisoxazole [9.18 g, 45.0 mmol) was dissolved in dry THF (315 mL). To the so- lution, 2M LDA (53 mL, 106.0 mmol) was dropwise added for 40 minutes at -78°C under nitrogen atmosphere, and the mixture was stirred for 15 minutes at the same conditions (at -78°C), to which THF solution (100 mL) of 4-isopropyl-5-iodomethyl-2-{4-trifluoromethyl)phenyl-thiazole (18.51 g, 45.0 mmol) was dropwise added for 45 minutes. The mixture was stirred for 1 hour under the same conditions (at -78°C), and allowed to room tempera¬ture. A saturated aqueous ammonium chloride solution and ethyl acetate were added to reaction the mixture. The ethyl acetate layer was washed with water and saline, dried over anhydrous sodium sulfate. After ethyl acetate was removed, the residue was purified by column chroma¬tography on silica gel with hexane/ethyl acetate (1/1) to give the desired compound (7.40 g) as pale yellow crys¬tals {yield 34%). iH-NMR (CDCI3, 400MHz) 6: 1.25 (d, 6H, J=7Hz), 2.25 (bs, 3H), 2.32 (s, 3H), 3.04 (m, IH), 3.26 (dd, 2H, J=6,8H2), 3.37 {dd, 2H, J=6,8Hz), 7.12 (bs, IH), 7.65 (d, 2H, J=8Hz), 7.99 (d, 2H, J=8Hz), 8.40 (bs, IH). (2) 6-Amino-3-[2-f4-isopropyl-2-(4- trifluoromethyl)phenyl-5-thiazolyl]ethyl]-5-methyl-l,2-benzisoxazole The obtained amide compound {18.0 g, 36.9 mmol) was suspended in 4M hydrochloric acid (360mL) and acetic acid (iSOmL). The suspension was refluxed for 24 hours, al¬lowed to room temperature, poured in to ice-cold water. and neutralized with ION aqueous sodium hydroxide solu¬tion. After ethyl acetate was added to the mixture, the organic layer was washed with saline, dried over anhy¬drous sodium sulfate. After the solvent was removed, the crude crystal in the residue was filtered, washed with hexane to give the desired compound (16.8 g) as pale brown crystal (yield 94%). iH-NMR (CDCI3, 400MHz) 5: 1.25 {d, 6H, J=7Hz), 2.21 (s, 3H), 3.05 (m, IH), 3.21 (dd, 2H, J=6,9Hz), 3.35 {dd, 2H, J=6,9H2), 4.01 (bs, 2H), 6.75 (s, IH), 7.14 (s, IH), 7.64 (d, 2H, J=8Hz), 8.00 (d, 2H, J=8Hz}. (3) 6-Hydroxy-3-[2-[4-isopropyl-2-(4- trifluoromethyl)phenyl-5-thiazolyl]ethyl]-5-methyl-l,2- benzisoxazole The obtained amine compound (15.4 g, 34.6 mmol) was suspended in 25% sulfuric acid (170 ml). An aqueous so¬dium nitrite solution (3.10 g, 45 mmol) was added to the suspension while cooling with ice. The mixture was stirred for 20 minutes under the same conditions, and dropwise added to 75% sulfuric acid heated at 130°C. The mixture was refluxed for 3 hours under the same conditions, allowed to room temperature, and poured into ice-cold water. After ethyl acetate were added to the mixture, the organic layer was dried over anhydrous sodium sulfate. After the solvent was removed, the crude crystal in the residue was filtered, and washed with hex¬ane to give the desired compound (8.36 g) as pale brown give the desired compound (8.36 g) as pale brown crystals (yield 54%). iH-NMR (CDCI3, 400MHz) 5: 1.24 (d, 6H, J=7Hz), 2.30 (s, 3H), 3.04 (m, IH), 3.2-3.4 (m, 4H), 5.30 (s, IH), 6.93 (s, IH), 7.22 (s, IH), 7. 65 (d, 2H, J=9Hz), 8.00 (d, 2H, J=9Hz). (4) Ethyl [3-I2-[4-lsopropyl-2-(4- trifluoromethyl)phenyl-5-thiazolyl]ethyl]-5-methyl-l,2-benzisoxazol-6-yl]oxyacetate The desired compound was obtained in an analogous manner as in (5) of Example 1. White powder Yield 65% iH-NMR (CDCI3, 400MHz) 5: 1.25 (d, 6H, J=7Hz), 1.31 (t, 3H, J=7Hz), 2.33 (s, 3H), 3.04(m, IH) , 3.2-3.4(m, 4H), 4.12(q, 2H, J=7Hz) 4.71 (s, 2H), 6.83 (s, IH), 7.25 (s, IH), 7.65 (d, 2H, J=9Hz), 8.00 (d, 2H, J=9Hz). (5) [3-[2- [4-Isopropyl-2-(4-trifluoromethyl)phenyl-5- thiazolyl]ethyl]-5-methyl-l,2-benzisoxazol-6-yl]oxyacetic acid The desired compound was obtained in an analogous ) manner as in {6) of Example 1. White powder Yield 71% mp (dec) 180-190°C iH-NMR (CDCI3, 400MHz) 6: I 1.24 (d, 6H, J=7Hz), 2.33 (s, 3H), 3.03 (m, IH), 3.2-3.4 (m, 4H), 4.77 (s, 2H), 6.87 (s, IH}, 7.26 (s, IH), 7.64 (d, 2H, J=9Hz), 7.99 (d, 2H, J=9Hz). IR(KBr)cm-l: 2960, 2930, 1740, 1620, 1520, 1450, 1420, 1320, 1280, 1250, 1160, 1120, 1060, 840. (Example 6) 2-[[3-[2-[4-Isopropyl-2-(4-trifluoromethyl)phenyl-5-thiazolyl] ethyl]-5-methyl-l,2-benzisoxazol-6-yl]oxy]-2-methylpropionic acid (1) Ethyl 2~[[3-[2-[4-isopropyl-2-(4- trifluoromethyl)phenyl-5-thiazolyl]ethyl]-5-methyl-l,2- benzisoxazol-6-yl]oxy]-2-methylpropionate The desired compound was obtained in an analogous manner as in (1) of Example 2. Pale yellow oil Yield 85% IH-NMR (CDC13, 400MHz) 5: 1.23 (d, 6H, J=7Hz), 1.24 (t, 3H, J=7H2}, 1.67 (s, 6H) 2.26 (s, 3H), 3.02 (m, IH), 3.2-3.4 (m, 4H), 4.25 (q, 2H, J=7Hz) 6.77 {s, IH), 7.25 (s, IH), 7.65 (d, 2H, J=9Hz), 8.00 (d, 2H, J=9Hz). (2) 2-[[3-[2-[4-Isopropyl-2-U-trifluoromethyl)phenyl-5-thiazolyl]ethyl]-5-methyl-l,2-benzisoxa2ol-6-yl]oxy]-2-methylpropionic acid The desired compound was obtained in an analogous manner as in {2) of Example 2. White crystal Yield 94% mp (dec) 166-168°C IH'NMR {CDC13, 400MHz) 8: 1.23 (d, 6H, J-7H2), 1.72 (s, 6H} 2.28 (s, 3H), 3.02 (m, IH), 3.2-3.4 (m, 4H), 5.93 (s, IH), 7.25 (s, IH), 7.65 (d, 2H, J=9H2), 8.00 (d, 2H, J=9Hz). IR(KBr)cm-l: 3000, 1720, 1620, 1520, 1450, 1370, 1320, 1280, 1160, 1120, 1060, 850, 820. (Example 7) [3-[2-[4-Isopropyl-2~ (4-trif luoro^lethyl)phenyl-5-thiazolyl] ethyl]-5-methyl-l,2-benEisoxazol-6-yl]thioacetic acid (1) 3-[2-[4-Isopropyl-2-(4-trifluoromethyl)phenyl-5-thiazolyl]-ethyl]-6-mercapto5-methyl-l,2-benzisoxazole 6-Ainino-3~ [2- [isopropyl-2- (4-trif luoromethyl} phenyl-5-thiazolyl]ethyl]-5-methyl-l,2-benzisoxazole (475 mg, 1.07 mmol} was dissolved in ethanol (3.3 mL) , Concen¬trated hydrochloric acid (1.68 mL) was added to the solu¬tion while cooling with ice (external temperature 0°C). Sodium nitrite (81 mg, 1.17 mmol) was added to the mix¬ture. An aqueous potassium xanthogenate solution (430 mg, 2.68 mmol) was dropwise added to the mixture for 5 min¬utes. The interreact temperature was kept at 45°C, and the mixture was stirred for 18 hours. The mixture was left to get cool, poured into water, and extracted with ethyl acetate. The organic layer was washed with saline, dried over anhydrous sodium sulfate. After the solvent was removed, the residue was purified by column chroma¬tography on silica gel with hexane/ethyl acetate (5/1) to give crude dithiocarbonic ester compound (131 mg). The dithiocarbonic ester compound was dissolved in ethanol. ' An aqueous solution of sodium hydroxide (36 mg) was added to the solution at room temperature. The mixture was re-fluxed for 3 hours. The reaction mixture was poured into ice-cold water, and neutralized with 1 M hydrochloric acid. After ethyl acetate was added to the mixture, the organic layer was washed with saline, dried over anhy¬drous sodium sulfate. After the solvent was removed, the residue was purified by column chromatography on silica gel with hexane/ethyl acetate (5/1) to give the desired compound (65 mg) (yield of the two steps 7%). 1 iH-NMR [CDCI3, 400MHz) 5: 1.23 (d, 6H, J=7HZ), 2.38 (s, 3H), 3.04 {m, IH), 3.2-3.4 (m, 4H), 3.60 (s, IH}, 7.26 (s, IH), 7.49 (s, IH) 7.65 (d, 2H, J=9HZ) , 8.00 (d, 2H, J=9H2). (2) Ethyl [[3-[2-[4-isopropyl-2-(4- trifluoromethyl)pheny1-5-thiazolyl]ethyl]-5-methyl-l,2-benzisoxazol-'6-yl] thio] acetate The desired compound was obtained in an analogous manner as in (5) of Example 1. Pale yellow oil Yield 69% iH-NMR (CDCI3, 400MHz) 5: 1.25 (d, 6H, J=7H2), 1.27 (t, 3H, J=7Hz}, 2.41 {s, 3H), 3.03 (m, IB), 3.2-3.4 (m, 4H), 3.76 (s, 2H), 4.22(q, 2H, J=7Hz) 7.27 (s, IH), 7.45 (s, IH), 7.65 (d, 2H, J=9Hz), 7.99 (d, 2H, J=9Hz). (3) [3-[2-[4-Isopropyl-2-(4-trifluoromethyl)phenyl-5-thiazolyl]ethyl]-5-methyl-l,2-benzisoxazol-6-ylj thioacetic acid The desired compound was obtained in an analogous manner as in (6) of Example 1. Pale yellowish white powder Yield 73% mp (dec) IVCC ^H-NMR (CDCI3, 400MHz) 5: 1.24 (d, 6H, J=7Hz), 2.42 (s, 3H}, 3.03 (m, IH), 3.2-3.4 (m, 4H), 3.81 (s, 2H), 7.28 (s, IH}, 7.46 (s, IH), 7.65 (d, 2H, J=9Hz}, 8.00 (d, 2H, J=9Hz). (Example 8) [3-[2-[4-Isopropyl-2-{4-trifluoromethyl)phenyl-5-thiazolyl]ethyl]-5-methyl-l, 2-benzisoxazol-6-yl]aminoacetic acid {1) Ethyl [3-[2-[4-isopropyl-2-(4- trifluoromethyl)phenyl-S-thiazolyl]ethyl]-5-methyl-l,2- benzisoxazol-6-yl]aminoacetate 6-Amino-3-[2-[4~isopropyl-2-(4-trifluoromethyl)phenyl-5-thiazolyl]ethyl]-5-methyl-l,2-benzisoxazole (445 mg, 1.00 mmol), ethyl bromoacetate (154 mg, 1.20 mmol), diisopropylethylamine (142 mg, 1.10 mmol) were dissolved in DMF (10 mL) . The solution was re-fluxed for 18 hours, poured into water, and extracted with ethyl acetate. The organic layer was washed with sa¬line, dried over anhydrous sodium sulfate. After the sol¬vent was removed, the residue was purified by column chromatography on silica gel with hexane/ethyl acetate (3/1) to give the desired compound (160 mg} as a dark brown powder (yield 30%) . ^H-NMR (CDCI3, 400MHz} 5: 1.25 {d, 6H, J=7Hz), 1.34 (t, 3H, J=7Hz), 2.25 (s, 3H), 3.05 (m, IH), 3.2-3.3 {m, 4H), 3.97 (d, 2H, J=3Hz} 4.6-4.7 (br, IH) 4.12 (q, 2H, J=7H2) 6.51 (s, IH), 7.15 (s, IH), 7.64 (d, 2H, J=9Hz), 8.00 (d, 2H, J=9Hz). (2) [3-[2-[4-Isopropyl-2~{4-trifluoromethyl)phenyl-5-thiazolyl]ethyl]-5-methyl-l,2-benzisoxa2ol-6-yljaminoacetic acid The desired compound was obtained in an analogous manner as in (6) of Example 1. Pale brown crystal Yield 73% mp (dec) 180-185°C iR-NMR {CDCI3, 400MHz) 5: 1.25 (d, 6H, J=7Hz), 2.25 (s, 3H), 3.04 (m, IH), 3.2-3.3 (m, 4H), 4.07 (s, 2H), 6.54 (s, IH), 7.15 (s, IH), 7.64 (d, 2H, J=9Hz), 7.99 (d, 2H, J=9Hz). IR(KBr)cm-l: 3425, 2950, 2925, 1740, 1620, 1520, 1440, 1380, 1370, 1320, 1220, 1160, 1060, 840. (Example 9) [3-[2-[2-(2,4-Dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyii-5-methyl-l,2-benzisoxazol-6-yl]oxyacetic acid (1) 6-Acetamido-3-[2-[2-(2,4-dichlorophenyl)-5- isopropyl-4-oxazolyl]ethyl]-5-methyl-l,2-benzisoxazole The desired compound was obtained in an analogous manner as in (1) of Example 5. Brown oil Yield 34% iH-NMR (CDCI3, 400MHz) 5: 1.10 (d, 6H, J=7Hz), 2.24 (bs, 3H), 2.26 (s, 3H), 2.92 (ra, IH), 3.05 (t, 2H, J=7Hz), 3.33 {t, 2H, J=7Hz), 7.16 (bs, IH), 7.28 (s, IH), 7.32 (dd, IH, J=2,9Hz), 7.51 (d, IH, J=2Hz), 7.91 (d, IH, J=9Hz), 8.34 (bs, IH). (2) 6-Amino-3-[2-[2-(2,4-dichlorophenyl)-5-isopropyl-4- oxazolyl]ethyl]-5-methyl-l,2-benzisoxazole The desired compound was obtained in an analogous manner as in (2) of Example 5. Yield 42% iH-NMR (CDCI3, 400MHz) 5: 1.10 (d, 6H, J=7H2), 2.14 (s, 3H), 2.92 (m, IH), 3.03 (t, 2H, J=7H2}, 3.27 (t, 2H, J=7Hz), 3.97 (bs, 2H), 6.72 (s, IH), 7.13 (s, IH), 7.32 (dd, IH, J-2,8Hz), 7.51 (d, IH, J=2Hz), 7.92 (d, IH, J=8Hz). (3) 3- [2-f2-(2,4-Dichlorophenyl)-5-isopropyl-4- oxazolyl]ethyl]- 6-hydroxy-5-methyl-l,2-benzisoxazole The desired compound was obtained in an analogous manner as in (3) of Example 5. Pale yellow crystal Yield 441 iH-NMR (CDCI3, 400MHz) 5: 1.11 (d, 6H, J=7Hz), 2.22 (s, 3H), 2.92 (m, IH}, 3.05 (t, 2H, J=7Hz), 3.29 (t, 2H, J=7Hz), 6.15 (bs, IH), 6.88 (s, IH), 7.19 (s, IH), 7.32 (dd, IH, J=2,9Hz), 7.51 (d, IH, J=2Hz), 7.90 {d, IH, J=9Hz). (4) Ethyl [[3-[2-[2-(2,4-dichlorophenyl)-5-isoprQpyl-4- oxazolyl]ethyl]-5-methyl-l,2-benzisoxazol-6-yl]oxyacetate The desired compound was obtained in an analogous manner as in (4) of Example 5. Yield 97% iH-NMR {CDCI3, 400MHz) 5: 1.11 (d, 6H, J=7Hz}, 1.30 (t, 3H, J=7Hz), 2.23 (s, 3H), 2.91 (m, IH), 3.04 (t, 2H, J=7Hz), 3.31 (t, 2H, J=7Hz), 4.28 (q, 2H, J=7Hz), 4.69 (s, 2H), 6.80 (s, IH), 7.24 (s, IH), 7.33 (dd, IH, J=2,8Hz), 7.51 (d, IH, J=2Hz), 7.91 (d, IH, J=8Hz). (5) [3-[2-[2-(2,4-Dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-5-methyl-l,2-benzisoxazol-6-yl]oxyacetic acid The desired compound was obtained in an analogous manner as in (5) of Example 5. Yield 88% Pale yellow crystal mp (dec) 180-184°C iH-NMR (CDCI3, 400MHz) 5: 1.11 (d, 6H, J=7Hz), 2.26 (s, 3H), 2.93 (ra, IH), 3.04 (t, 2H, J=7Hz), 3.30 (t, 2H, J=7Hz), 4.76 (s, 2H) 5.84 (s, IH), 7.23 (s, IH), 7.33 (dd, IH, J=2,8Hz), 7.64 (d, IH, J=2H2), 7.99 (d, IH, =8Hz). IR(KBr)cm-l:1749, 1718, 1625, 1562, 1521, 1457, 1446, 1429, 1388, 1361, 1317, 1284, 1251, 1162, 1103, 1087, 1041, 898, 863, 831, 817, 775, 732, 674, 667, 611. (Example 10) 2-[ [3- [2-[4-Isopropyl-2-(4-trifluoromethyl)phenyl-5-thiazolyl] ethyl] -5-inethyl-l, 2-benzisoxazol-6-yl] oxy] -2-methylpropionic acid 2-piperidin-l-yl ethyl ester hydro¬chloride 2-[[3-[2-[4-lsopropyl-2-{4-trifluoromethyl)phenyl-5-thiazolyl]ethyl]-5-methyl-l,2-benzisoxazol-6-yl]oxy]-2-methylpropionic acid (247 mg, 0.463 mmol) was dissolved in dichXoromethane (10.0 raL) . To the solution, oxalyl chloride (0.053 mL, Q.60 mmol) and DMF (1-drop) were added while cooling with ice. The mixture was allowed to room temperature, and stirred for 3 hours under nitrogen atmosphere. The solvent was removed under reduced pres¬sure. The acid chloride compound in the residue was dis¬solved in dichloromethane (10.0 mL) . To the solution, piperidine-2-ethanol {90 mg, 0.70 mmol), triethylamine (71 mg, 0.70 mmol) and 4-dimethylaminopyridine (3 mg) were added. The mixture was stirred for 20 hours at room temperature, and poured into ice-cold water. After ethyl acetate was added to the mixture, the organic layer was washed with saline, and then with water, dried over anhy¬drous sodium sulfate. After the solvent was removed under reduced pressure, the residue was purified by column chromatography on silica gel with hexsne/ethyl acetate (3/1) to give 2-[[3-[2-[4-isopropyl-2-(4-trifluoromethyl)phenyl-5-thiazolyl]-ethyl]-5-methyl-l,2-benzisoxazol-6-yl]oxy]-2-ro.ethylpEoplonic acid 2-piperidin-1-yl ethyl ester (190 mg) as colorless oil. The ester compound was dissolved in diethyl ether (4.0 mL) . To the solution, hydrogen chloride-diethyl ether solution was added. Crystals were filtered to give the desired compound (160 mg) as white crystal (yield 51%). mp 75-80'C iH-NMR (CDCI3, 400MHz) 6: (Free) 1,24 (d, 6H, J=7Hz), 1.3-1.4 (m, 2H), 1.5-1.6 (m, 4H} 1.68 (s, 6H), 2.26 (s, 3H), 2.3-2.4 (m, 4H) , 2.55 (t, 2H, J=6Hz), 3.04 (m, IH), 3.23 (t, 2H, J=8Hz), 3.34 (t, 2H, J-8HZ), 4.31 (t, 2H, J=6Hz}, 6.B6 (s, IH), 7.23 (s, IH), 7.65 (d, 2H, J=9Hz), 8.00 {d, 2H, J=9Hz). (Example 11) (Pharmacological experiment 1) (1) Measurement of PPARa, y, 6 transactivation activity PPARa, Y' 2 transactivation activity of each compound [Examples 1-4] was measured in the manner described be-Low. [. Method -) Material CV-1 cells were obtained from Tohoku University Ag-.ng Medical Laboratory, Medical Cell Collection Center, dl test coinpounds were dissolved in dimethyl sulfoxide DMSO) , Final concentration of DMSO was 0.1%. 2} Plasmid Receptor expression plasmid (GAL4-hPPARa, LBD GAL4-hPPARy LBD, GAL4-hPPAR5 LBD), Reporter plasmid (UASx4-TK-LUC), and P-galactosidase expression plasmid (pGAL) simi¬lar to Kliewer, S.A., et al., ((1992) Nature, 358:771-774) were used. 3) Transfection CV-1 cells were seeded in 24 well culture plates at 2x10^ cells per well, and cultured for 24 hours OPTI-MEM I Reduced Serum Medium (Life Technologies, 500 pL/well) containing 4%-fetal bovine serum (FBS). After washing with OPTI-MEM, transfection mixture (250 .pL/well} con¬taining 0.03 pg of GAL4-hPPAR5 LBD, 0.25 pg of UASx4-TK-LUC, 0.35 pg of PCAL, and 2 pL of lipofection reagent, DMRIE-C (Life Technologies) were added. The cells were incubated for 5 hours at 37°C. 4) Cell treatment by addition of test compound The cells were washed and incubated for 4 0 hours in the presence of the test compound (final concentration was IQ-^M). 5) Measurement of the level of reporter gene expression The culture medium was removed and the cells were washed with PBS twice. A solubilizing buffer (100 pL/well) containing 25 mM Tris-P04 (pH 7.8}, 15%v/v glyc¬erol, 2% CHAPS, 1% Lecithin, 1% BSA, 4 raM EGTA (pH 8.0), 8 mM MgCl2, 1 mM DTT was added. After the incubation for 10 minutes at room temperature, a portion (20 yL) of the solution was transferred into a 96-well plate. Subse¬quently, 100 pL of luciferase substrate solution (Pic-cagene: available from Nippon Gene Co., Ltd.} was added, and a luminous intensity per one second (luciferase ac- tivity) was measured using a microluminoreader (Type MLR-100, Corona Electrics Co., Ltd.). Each luciferase ac-tivety was corrected by the transfection efficiency which was calculated from p-galactosidase activity. The assay ) method of p-galactosidase activity was as follows: A por¬tion (50 liL) of the solubilized sample was transferred into another 96-well plate; 100 pL of ONPG [2-nitrophenyl-p-galactopyranoside) solution was added and incubated for 5 minutes at room temperature. 50 pL of a I reaction stopping solution (IM sodium carbonate solution) was added. Then the absorbance at 414 nm was measured. A relative PPAR activity was calculated as follows: 0% (luciferase activity of cells treated with DMSO (0.1%) alone), 100% (luciferase activity of cells treated with a control (PPARa: 10"^ M wy-165041, PPARy: lO'^ M Rosiglita-zone, PPAR6: 10-*^ M L-165041)). II. Results The results are shown in Table 25. TABLE 25 a y 5 Example 1 0.1 9.4 76.9 Example 2 8.0 3.2 67.8 Example 4 85.0 9.5 59.9 It is clear from Table 25 that the compounds of Ex¬amples have potent PPAR6 transactivation activity. Par- ticularly, the compounds of Examples 1 and 2 show selec¬tive PPAR5 transactivation activity. (Example 52) (Pharmacological tests 2) PPAR transactivation activities of the compounds of Examples 5-10 were assayed in the same manner as de¬scribed in Example 11. The results are shown in Table 26. TABLE 2 6 Test compound a y 6 Example 5 0 0 75 Example 6 0 0 54 Example 7 0 0 63 Example 8 0 0 61 Example 9 0 2 86 Example 10 3 0 75 GW-2433 64 7 52 GW-501516 0 1 90 Relative activities for PPAR transactivation were shown. Each value represents as % of control. Cells were cultured in the presence of compounds at 10"^ M except that PPAR5 of Examples 5, 6 and 7 were assayed at 10'^ M. Positive control: a: 10-^ M WY-14643 y: 10"^ M Rosiglitazone 5: 10-" M L-165041 It is clear from Table 26 that the compounds of Ex¬amples 6-10 have potent and selective PPAR5 transactiva- tion activities, i (Example 13) (Pharmacological experiment 2) HDL cholesterol elevating effect I. Method HDL cholesterol elevating effect was measured by us¬ing db/db mice, which are hereditary obesity mice. The db/db mice (10 weeks old) were divided into groups tased on serum HDL cholesterol levels. Each of the compounds of the present invention (compounds synthesized in Examples 4 and 10) and GW-501516 was orally administered for one week twice daily. Mice of the control group (to which no agent was administered) were orally given 1% methyl cel¬lulose solution. After 16 hours from the final admini¬stration, blood sample was collected, and serum HDL cho¬lesterol level was measured. HDL cholesterol was sepa¬rated by electrophoresis on agarose gels (Choi/Trig Combo, Helena Laboratories). Serum total cholesterol lev¬els were measured enzymaticallly using a kit (Pure Auto, Daiichi Chemicals) by an automatic analyzer (7060E type, Hitachi Ltd.). HDL cholesterol levels were calculated from total cholesterol levels and HDL cholesterol/total cholesterol ratios. II. Results Serum HDL cholesterol levels of experiments groups are shown in Table 27. Each value represents as % of the control group. TABLE 27 Test com- Dose Ratio of increasing HDL cho-pound (mg/kg/b.i-d.) lesterol (% to control) Example 6 10 164 GW-501516 10 149 As shown in Table 6, the compound obtained in Exam¬ple 6 has a potent HDL cholesterol elevating effect. VJE CLAIM : 1. A compound having the following formula (1) or a salt thereof: R^ is aryl, which can be substituted with a group or atom selected from the group consisting of Cj-g alkyi, Ci_ 3 alkoxy, C^^s alkyl substituted with 1-3 halogens, Hy-droxyl, nitro, amino, phenyl, pyridyl and halogen, or a heterocyclic group having five to eight membered ring comprising one to three hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur and the other atoms consisting of carbon (benzene ring can he condensed with the heterocyclic ring); R2 is C2-.a alkyl, C^.g alkyl substituted with 1-3 halogens, 03.7 cycloalkyl/ C2_a alkenyl, C2-B alkynyl, al¬kyl (comprising Cj_j alkyl moiety) substituted with aryl, which can be substituted with a group or atom selected from the group consisting of C]^_g alkyl, C^.g alkoxy, C^^g alkyl substituted with 1-3 halogens, hydroxyl, nitro, amino, phenyl, pyridyl and halogen, or alkyl (comprising €2^,4 alkyl moiety) substituted with a heterocyclic group having five to eight membered ring (comprising one to three hetero atoms selected from the group consisting of nitrogen, oxygen and sulfur and the other atoms consist¬ing of carbon); R3 is halogen, trifluoromethyl, C^.g alkyl, C2_g al-kenyl or C2_g alkynyl; each of R'* and R^ is hydrogen, C^^g alkyl or C]^„g al¬kyl substituted with 1-3 halogens; and R6 is hydrogen, Cj^_g alkyl substituted with amino, C]^_g alkyl or alkali metal; provided that each of Z and R^ is attached to the benzene ring, and X^ is not attached to the benzene ring. 2. A compound or a salt of thereof defined in claim 1, wherein R^ is attached to the 2nd position of the oxazole, thiazole or imidazole ring. 3. A compound or a salt thereof defined in claim 1 or 2, wherein B^ is N, and B^ is O. 4. A compound or a salt thereof defined in any one of claims 1 to 3, wherein R^ is hydrogen. 5. A compound or a salt thereof defined in any one of claims 1 to 4, wherein X^ is a bond. 6. A compound or a salt thereof defined in any one of claims 1 to 5, wherein X^ is a bond. 7. A compound or a salt thereof defined in any one of claims 1 to 6, wherein Ri is aryl substituted with a group or atom selected from the group consisting of C]^_g alkyl, Ci^Q alkoxy, C^.g alkyl substituted with 1-3 halo¬gens, hydroxyl, nitro, amino, phenyl, pyridyl and halo¬gen. 8. A compound or a salt thereof defined in any one of claims 1 to 7, wherein R^ is C2_8 alkyl. 9. A compound or a salt thereof defined in any one of claims 1 to 8, wherein R^ is C]^_g alkyl or Cg-e alkenyl. 10. An activator of peroxisome proliferator acti¬vated receptor 8 which contains as an effective component a compound or a salt thereof defined in any one of claims 1 to 9. 11. A compound having the following formula substantially as herein described and exemplified.

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