PPAR-GAMMA MODULATORS

摘要

Modulators of PPAR gamma activity are provided having formula (I): in which the symbol Ar represents an aryl group; the letter X represents a divalent linkage selected from the group consisting of =C1-C6alkylene, -(C1-C6)alkylenoxy, -O-, -C(O)-, -N(R<11>)-, -N(R<11>)C(O)-, -S(O)k- and a single bond, in which R<11> is a member selected from the group consisting of hydrogen, alkyl, heteroalkyl, and arylalkyl and the subscript k is an integer of from 0 to 2. The letter Y, in formula (I) represents a divalent linkage selected from the group consisting of alkylene, -O-, -C(O)-, -N(R<12>)-S(O)m-, -N(R<13>)-S(O)m-N(R<13>)-, -N(R<12>)C(O)-, -S(O)n-, a single bond, and combinations thereof in which R<12> and R<13> are members independently selected from the group consisting of hydrogen, alkyl, heteroalkyl and arylalkyl; and the subscripts m and n independently integers of from 0 to 2. The symbol R<1> represents a member selected from the group consisting of hydrogen, alkyl, heteroalkyl, aryl, arylalkyl, -CO2R<14>, -CO(R)<14>, -C(O)NR<15>R<16>, -S(O)p-R<14>, -S(O)q-NR<15>R<16>, -O-C(O)-OR<17>, -O-C(O)-R<17>, -O-C(O)-NR<15>R<16>, -N(R<14>)-C(O)-NR<15>R<16>, -N(R<14>)-C(O)-R<17> and -N(R<14>)-C(O)-OR<17>, in which R<14> is a member selected from the group consisting of hydrogen, alkyl, heteroalkyl, aryl and arylalkyl, and R<15> and R<16> are members independently selected from the group consisting of hydrogen, alkyl, heteroalkyl, aryl and arylalkyl, or taken together with the nitrogen to which each is attached from a 5-, 6- or 7-membered ring. The symbol R<17> represents a member selected from the group consisting of alkyl, heteroalkyl, aryl and arylalkyl. Additionally, for the R<1> groups described above, the subscript p is an integer of from 0 to 3, and the subscript q is an integer of from 1 to 2. The symbol R<2> represents a member selected from the group consisting of alkyl, heteroalkyl, aryl and arylalkyl. In another aspect, the present invention provides compounds of formula (I), as well as pharmaceutical compositions containing the compounds described above for the treatment of conditions such as type II diabetes and obesity.