Fused heterocyclic derivatives as PPAR modulators

A compound of the structural Formula VIII:

• or a pharmaceutically acceptable salt thereof, wherein:
• (a) R26, R27, R28 and R31 are each independently selected from the group consisting of hydrogen, hydroxy, cyano, nitro, halo, oxo, C1-C6 alkyl, C1-C6 alkyl-COOR12, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkyloxy, C3-C7 cycloalkyl, aryloxy, aryl-C0-4-alkyl, heteroaryl, heterocycloalkyl, C(O)R13, COOR14, OC(O)R15, OS(O)2R16, N(R17)2, NR18C(O)R19, NR20SO2R21, SR22, S(O)R23, S(O)2R24, and S(O)2N(R25)2;
• R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24 and R25 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl and aryl;
• (b) X is selected from the group consisting of a O, S, S(O)2 and N;
• (c) U is an aliphatic linker of C1-C3 alkyl;
• (d) Y is selected from the group consisting of C, O, S, NH, and a single bond;
• (e) E is C(R3)(R4)A and wherein
• (i) A is selected from the group consisting of carboxyl, C1-C6 alkylnitrile, carboxamide, sulfonamide and acylsulfonamide;
• wherein sulfonamide, and acylsulfonamide are each optionally substituted with from one to two groups independently selected from R7;
• (ii) each R7 is independently selected from the group consisting of hydrogen, C1-C6 haloalkyl, aryl C0-C4 alkyl and C1-C6 alkyl;
• (iii) R3 is selected from the group consisting of hydrogen, and C1-C5 alkyl;
• and
• (iv) R4 is selected from the group consisting of H and C1-C5 alkyl, and wherein alkyl, alkoxy, aryloxy, cycloalkyl and aryl-alkyl are each optionally substituted with one to three substituents each independently selected from R26;
• (f) B is selected from the group consisting of N, S and O;
• (g) Z is selected from the group consisting of N and C;
• (h) R8 is selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkylenyl, and halo;
• (i) R9 is selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkylenyl, halo, aryl-C0-C4 alkyl and wherein aryl-C0-C4 alkyl is optionally substituted with from one to three independently selected from R27;
• R8 and R9 optionally combine to form a five membered fused bicyclic with the phenyl to which R8 and R9 attach, provided that when R8 and R9 form a fused ring, the group E-Y— is bonded at any available position on the five membered ring of such R8 and R9 fused bicyclic;
• (j) R10, R11 are each independently selected from the group consisting of hydrogen, hydroxy, cyano, nitro, halo, oxo, C1-C6 alkyl, C0-C6 alkoxy, and C1-C6 haloalkyl;
• (k) R30 is selected from the group consisting of C1-C6 alkyl, aryl-C0-4-alkyl, aryl-C1-4-heteroalkyl, heteroaryl-C0-4-alkyl, and C3-C6 cycloalkylaryl-C0-2-alkyl, and wherein C1-C6 alkyl, aryl-C0-4-alkyl, aryl-C1-4-heteroalkyl, heteroaryl-C0-4-alkyl, and C3-C6 cycloalkylaryl-C0-2-alkyl are each optionally substituted with from one to three substituents each independently selected from R31;
• and
• (l) R32 is selected from the group consisting of hydrogen, halo, C1-C6 alkyl, C1-C6 haloalkyl, and C1-C6 alkyloxo.