1,3,4-oxadiazol-2-ones as PPAR delta modulators

摘要

Disclosed is a compound of formula I wherein ARYL is phenyl or pyridinyl, wherein said phenyl or pyridinyl is optionally substituted with one or more substituents selected from the group consisting of halogen, C1-6 alkyl, C1-6 alkenyl, C1-6 alkoxy, C1-6 perfluoroalkyl; C1-6 alkylthio, hydroxy, hydroxyC1-6 alkyl, C1-6 acyloxy, nitro, cyano, C1-6 alkylsulfonyl, amino, C1-6 alkylamino and C1-6 alkoxycarbonyl; W is a bond or (CH2)m, wherein m is an integer from 1 to 4; Z is -O(CH2)n-, -SO2(CH2)n-, -(CH2)n-Y-(CH2)n-,-(CH2)n-CO-, -O(CH2)n-CO- or -(CH2)n-Y-(CH2)n-CO- wherein Y is NR3, O or S and R3 is selected from the group consisting of H, C1-6 alkyl C3-8 cycloalkyl, C1-6 alkyl C3-8 cycloalkyl and benzyl and n is independently an integer from 1 to 5; X is NR3, O or S wherein R3 is as defined above; R1 is H, halogen, C 1-6 alkyl, C1-6 alkoxy, C 1-6 perfluoroalkyl; hydroxyC1-6 alkyl, nitro, cyano,and C1-6 alkylamino; and R2 is substituted or unsubstituted phenyl, pyridinyl or thienyl wherein the substituents are selected from the group consisting of halogen, C1-6 alkyl, C2-6 alkenyl, C1-4.alkoxy, C1-4 perfluoroalkyl, C1-6 alkylthio, hydroxy, hydroxyC1-6 alkyl, C1-4 acyloxy, nitro, cyano,C1-6 alkylsulfonyl, amino, C1-6 alkylamino and C1-6 alkoxycarbonyl; or a stereoisomer, tautomer or a solvate thereof or a pharmaceutically acceptable salt thereof. The compounds are selective ppARdelta ligand receptor binders, which are useful in modulating ppARdelta receptors for the treatment of diseases mediated by nuclear hormone receptors.