PPAR agonists

A compound of the Formula I

• 6
• a prodrug thereof, or a pharmaceutically acceptable salt of said compound or of said prodrug;
• wherein
• E is carbonyl or sulfonyl;
• B is methylene or —N(H)—;
• Z is carboxyl, carboxaldehyde, hydroxymethyl, (C1-C4)alkoxycarbonyl, cyano, hydroxyaminocarbonyl, tetrazolyl, tetrazolylaminocarbonyl, 4,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl, 3-oxoisoxazolidin-4-yl-aminocarbonyl, or —C(O)N(H)SO2R4;
• where R4 is (C1-C6)alkyl, amino or mono-N- or di-N,N-(C1-C6)alkylamino, said (C1-C6)alkyl substituents are optionally substituted independently with from one to nine fluorines;
• W is a bond, —N(H)—, —N((C1-C4)alkyl)- (C1-C4)alkylamino, or (C1-C8)alkylene;
• wherein said (C1-C8)alkylene may optionally be mono- or di-substituted independently with oxo, halo, (C1-C6)alkoxycarbonyl, (C1-C6)alkyl, (C2-C6)alkenyl, (C3-C7)cycloalkyl, hydroxy, (C1-C6)alkoxy, (C1-C4)alkylthio, amino, cyano, nitro, or mono-N- or di-N,N-(C1-C6)alkylamino or
• wherein W is CR7R8 wherein R7 and R8 are linked together to form a three to six membered fully saturated carbocyclic ring;
• R1 is H, (C1-C6)alkyl or (C3-C6)cycloalkyl;
• R2 is H, a (C3-C6)cycloalkyl or a fully saturated, partially unsaturated or fully unsaturated one to four membered straight or branched carbon chain wherein the carbon(s) may optionally be replaced with one or two heteroatoms selected independently from oxygen and sulfur and wherein said carbon(s) is optionally mono-, di- or tri-substituted independently with halo, said carbon(s) is optionally mono-substituted with hydroxy, said carbon(s) is optionally mono-substituted with oxo, said sulfur is optionally mono- or di-substituted with oxo, and said chain is optionally mono-substituted with Y;
• wherein Y is a partially saturated, fully saturated or fully unsaturated three to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, said bicyclic ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen;
• wherein said Y ring is optionally mono-, di- or tri-substituted independently with halo, (C2-C6)alkenyl, (C1-C6) alkyl, hydroxy, (C1-C6)alkoxy, (C1-C4)alkylthio, amino, nitro, cyano, oxo, carboxy, (C1-C6)alkyloxycarbonyl, mono-N- or di-N,N-(C1-C6)alkylamino wherein said (C1-C6)alkyl substituent is optionally mono-, di- or tri-substituted independently with halo, hydroxy, (C1-C6)alkoxy, (C1-C4)alkylthio, amino, nitro, cyano, oxo, carboxy, (C1-C6)alkyloxycarbonyl, mono-N- or di-N,N-(C1-C6)alkylamino, said (C1-C6)alkyl substituent is also optionally substituted with from one to nine fluorines;
• or
• R1 and R2 are linked together to form a three to six membered fully saturated carbocyclic ring optionally having one heteroatom selected from oxygen, sulfur and nitrogen;
• R3 is (C1-C10)alkyl, (C2-C10)alkenyl or (C2-C10)alkynyl, said (C1-C10)alkyl, (C2-C10)alkenyl or (C2-C10)alkynyl substituents are optionally mono-, di- or tri-substituted independently with halo, hydroxy, (C1-C6)alkoxy, (C1-C4)alkylthio, amino, nitro, cyano, oxo, carboxy, (C1-C6)alkyloxycarbonyl, or mono-N- or di-N,N-(C1-C6)alkylamino or optionally
• said (C1-C10)alkyl, (C2-C10)alkenyl or (C2-C10)alkynyl substituents are mono-substituted with a partially saturated, fully saturated or fully unsaturated five to six membered ring optionally having one to two heteroatoms selected from nitrogen, oxygen and sulfur, or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, said bicyclic ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen;
• said ring optionally mono-, di- or tri-substituted independently with halo, (C2-C6)alkenyl, (C1-C6) alkyl, hydroxy, (C1-C6)alkoxy, (C1-C4)alkylthio, amino, nitro, cyano, oxo, carboxy, (C1-C6)alkyloxycarbonyl, mono-N- or di-N,N-(C1-C6)alkylamino wherein said (C1-C6)alkyl substituent is optionally mono-, di- or tri-substituted independently with halo, hydroxy, (C1-C6)alkoxy, (C1-C4)alkylthio, amino, nitro, cyano, oxo, carboxy, (C1-C6)alkyloxycarbonyl, mono-N- or di-N,N-(C1-C6)alkylamino, said (C1-C6)alkyl substituent is also optionally substituted with from one to nine fluorines;
• R5 and R6 are linked together to form a three to six membered fully saturated carbocyclic ring or are each independently H, (C1-C6)alkyl, (C3-C7)cycloalkyl or (C3-C7)cycloalkyl(C1-C6)alkyl;
• and
• A is H, mono-N- or di-N,N-(C1-C6)alkylamino, (C2-C6)alkanoylamino, (C1-C6)alkoxy, or a partially saturated, fully saturated or fully unsaturated three to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or a bicyclic ring consisting of two fused partially saturated, fully saturated or fully unsaturated three to six membered rings, taken independently, said bicyclic ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen;
• and
• wherein said A ring is optionally mono-, di- or tri-substituted independently with oxo, carboxy, halo, (C1-C6)alkoxycarbonyl, (C1-C6)alkyl, (C2-C6)alkenyl, (C3-C7)cycloalkyl, (C3-C7)cycloalkyl(C1-C6)alkyl, hydroxy, (C1-C6)alkoxy, (C1-C4)alkylthio, amino, cyano, nitro, or mono-N- or di-N,N-(C1-C6)alkylamino wherein said (C1-C6)alkyl or (C1-C6)alkoxy substituents are optionally mono-, di- or tri-substituted independently with halo, hydroxy, (C1-C6)alkoxy, amino, mono-N- or di-N,N-(C1-C6)alkylamino or from one to nine fluorines, or
• wherein said A ring is optionally mono-substituted with a partially saturated, fully saturated or fully unsaturated three to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen.