Peroxisome proliferator activated receptor alpha agonists

A compound represented by the following structural Formula I:

• and pharmaceutically acceptable salts, solvates and hydrates thereof, wherein:
• (a) R1 is selected from the group consisting of hydrogen, substituted or unsubstituted group selected from C1-C8 alkyl, aryl-C0-4-alkyl, heteroaryl-C0-4-alkyl, C3-C6 cycloalkylaryl-C0-2-alkyl, and —CH2—C(O)—R17-R18, wherein R17 is O or NH and R18 is optionally substituted benzyl;
• (b) W is O;
• (c) R2 is H or a substituted or unsubstituted group selected from the group consisting of C1-C6 alkyl, C1-C6 allyl, aryl-C0-4-alkyl, heteroaryl-C0-4-alkyl, sulfonamide, amide, OR10 and C3-C6 cycloalkyl;
• (d) X is an optionally substituted C2 C5 alkylene linker;
• (e) Y is O, S, or NH;
• and
• (f) E is selected from the group consisting of A, C(R3)(R4)A,
• (CH2)n COOR19 wherein the (CH2)n COOR19 moiety is substituted or unsubstituted with from one to three substituents each independently selected from the group consisting of C1-C5 alkyl, C1-C5 alkoxy,
• C1-C5 haloalkyl, C1-C5 haloalkoxy, nitro, cyano, CHO, hydroxyl, C1-C4 alkanoic acid phenyl, aryloxy, SO2R7, SR7, benzyloxy, alkylcarboxamido, and COOH, wherein R7 is alkyl or haloalkyl,
• wherein
• (i) n is 0, 1, 2 or 3,
• (ii) A is a moiety selected from the group consisting of carboxyl, C1-C3alkylnitrile, carboxamide, substituted or unsubstituted sulfonamide, substituted or unsubstituted acylsulfonamide and substituted or unsubstituted tetrazole;
• (iii) R3 is H, saturated or unsaturated C1-C5 alkyl, C1-C5 alkoxy, and
• (iv) R4 is H, halo, a substituted or unsubstituted group selected from C1-C5 alkyl, C1-C5 alkoxy, C3-C6 cycloalkyl, aryl C0-C4 alkyl and phenyl, or R3 and R4 are combined to form a C3-C4 cycloalkyl;
• (v) R19 is selected from the group consisting of hydrogen, optionally substituted arylmethyl and optionally substituted C1 -C4alkyl;
• (vi) R14 is selected from the group consisting of CF3, substituted or unsubstituted phenyl, substituted or unsubstituted aryl-C0-C4 alkyl, and C1-C6 alkyl;
• (g) R8 is independently selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkylenyl, and halo;
• (h) R9 is independently selected from the group consisting of hydrogen, C1-C4 alkyl, C1-C4 alkylenyl, halo, substituted or unsubstituted aryl, substituted or unsubstituted aryl-C-C4 alkyl, substituted or unsubstituted heteroaryl, C1-C6 allyl, and OR10;
• and R10 is independently selected from the group consisting of hydrogen and C1-C4 alkyl.