Novel phenylpropionic acid derivatives as peroxisome proliferator-activated gamma receptor modulators, method of the same, and pharmaceutical composition comprising the same

A method for preparing a compound of formula 1, comprising:

• (1) reacting a compound of formula 2 with a compound of formula 3, 4, 5 or 6 to form a compound of formula 7, 8, 9 or 10;
• and
• (2) reacting the compound of formula 7, 8, 9 or 10 with a boron compound of formula 11 to form a compound of formula 1 wherein R1 is ethyl:
• wherein:
• R1 is hydrogen, ethyl, or an alkali metal;
• R2 is hydrogen or methyl;
• X is S or O;
• Y is N or CH;
• R3 is hydrogen, lower alkyl or lower alkoxy;
• R4 is hydrogen, lower alkyl, lower alkoxy, halide, cyano, acetyl, acetamino, benzoyl, carbamoyl, alkylcarbamoyl, aminosulfonyl, 2-H-benzo[b][1,4]oxazine, morpholine, thiazole, morpholinosulfonyl, morpholinocarbonyl, 4,5-dihydropyridazin-3(2H)-one, thiadiazole, oxadiazole, tetrazole, oxazole, or isoxazole, each of which being optionally substituted by at least one selected from the group consisting of hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, hydroxy, amino, trifluoromethyl, phenyl, benzyl, benzoyl, furan, thiophene, piperidine and morpholine;
• and
• n is an integer of 1 to 5.

A pharmaceutical composition for modulation of peroxisome proliferator-activated receptor gamma (PPAR-γ), comprising a compound represented by formula 1, an optical isomer thereof or a pharmaceutically acceptable salt thereof, as an active ingredient:

• wherein:
• R1 is hydrogen, ethyl, or an alkali metal;
• R2 is hydrogen or methyl;
• X is S or O;
• Y is N or CH;
• R3 is hydrogen, lower alkyl or lower alkoxy;
• R4 is hydrogen, lower alkyl, lower alkoxy, halide, cyano, acetyl, acetamino, benzoyl, carbamoyl, alkylcarbamoyl, aminosulfonyl, 2-H-benzo[b][1,4]oxazine, morpholine, thiazole, morpholinosulfonyl, morpholinocarbonyl, 4,5-dihydropyridazin-3(2H)-one, thiadiazole, oxadiazole, tetrazole, oxazole, or isoxazole, each of which being optionally substituted by at least one selected from the group consisting of hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, hydroxy, amino, trifluoromethyl, phenyl, benzyl, benzoyl, furan, thiophene, piperidine and morpholine;
• and
• n is an integer of 1 to 5.