Ppar activators

A compound of Formula I

• an isomer thereof, a prodrug of said compound or isomer, or a pharmaceutically acceptable salt of said compound, isomer or prodrug;
• wherein m and n are each independently one or two;
• V and Y are each independently a) methylene, or b) carbonyl;
• F and G are each independently a) hydrogen, b) halo, c) (C1-C4)alkyl optionally substituted with one to nine fluoro, d) (C3-C6)cycloalkyl, e) hydroxy, f) (C1-C4)alkoxy or g) (C1-C4)alkylthio;
• X is a) -Z or b) -B-C(R1R2)-Z;
• B is a) oxy, b) thio, c) sulfinyl, d) sulfonyl, e) methylene, or f) —N(H)—;
• Z is a) —C(O)OH, b) —C(O)O—(C1-C4)alkyl, c) —C(O)O—(C0-C4)alkyl-aryl, d) —C(O)—NH2, e) hydroxyaminocarbonyl, f) tetrazolyl, g) tetrazolylaminocarbonyl, h) 4,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl, i) 3-oxoisoxazolidin-4-yl-aminocarbonyl, j) —C(O)N(H)SO2R4, or k) —NHSO2R4;
• wherein R4 is a) (C1-C6)alkyl, b) amino or c) mono-N— or di-N,N—(C1-C6)alkylamino, wherein the (C1-C6)alkyl substitutents in R4 are optionally independently substituted with one to nine fluoro;
• R1 is a) H, b) (C1-C4)alkyl, or c) (C3-C6)cycloalkyl;
• R2 is a) H, b) (C3-C6)cycloalkyl or c) a fully or partially saturated or fully unsaturated one to four membered straight or branched carbon chain;
• wherein the carbon(s) in the carbon chain may optionally be replaced with one or two heteroatoms selected independently from oxygen and sulfur;
• and wherein the sulfur is optionally mono- or di-substituted with oxo;
• wherein the carbon(s) in the carbon chain in R2 is optionally independently substituted as follows:
• a) the carbon(s) is optionally mono-, di- or tri-substituted independently with halo, b) the carbon(s) is optionally mono-substituted with hydroxy or (C1-C4)alkoxy, and c) the carbon(s) is optionally mono-substituted with oxo;
• and
• wherein the carbon(s) in the carbon chain in R2 is optionally mono-substituted with Q;
• wherein Q is a partially or fully saturated or fully unsaturated three to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or is a bicyclic ring consisting of two fused partially or fully saturated or fully unsaturated three to six membered rings, taken independently;
• wherein the bicyclic ring optionally has one to four heteroatoms selected independently from oxygen, sulfur and nitrogen;
• wherein the Q ring is optionally mono-, di- or tri-substituted independently with a) halo, b) (C2-C6)alkenyl, c) (C1-C6) alkyl, d) hydroxy, e) (C1-C6)alkoxy, f) (C1-C4)alkylthio, g) amino, h) nitro, i) cyano, j) oxo, k) carboxy, l) (C1-C6)alkyloxycarbonyl, or m) mono-N— or di-N,N—(C1-C6)alkylamino;
• wherein the (C1-C6)alkyl and (C1-C6)alkoxy substitutents on the Q ring is optionally mono-, di- or tri-substituted independently with a) halo, b) hydroxy, c) (C1-C6)alkoxy, d) (C1-C4)alkylthio, e) amino, f) nitro, g) cyano, h) oxo, i) carboxy, j) (C1-C6)alkyloxycarbonyl, or k) mono-N— or di-N,N—(C1-C6)alkylamino;
• wherein the (C1-C6)alkyl substitutent is on the Q ring is also optionally substituted with one to nine fluoro;
• or wherein 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 to form a heterocyclic ring;
• E is a) carbonyl, b) sulfonyl, or c) methylene;
• W is a) a bond, b) carbonyl, c) —N(H)—, d) —N((C1-C4)alkyl)-, e) (C2-C8)alkenyl, f) oxy, g) —(C1-C4)alkyl-O—, h) —NH—(C1-C4)alkyl-, or i) —(C1-C6)alkyl-;
• wherein the (C1-C6)alkyl and the (C2-C8)alkenyl groups in W may optionally be mono- or di-substituted independently with a) oxo, b) halo, c) (C1-C6)alkoxycarbonyl, d) (C1-C6)alkyl, e) (C2-C6)alkenyl, f) (C3-C7)cycloalkyl, g) hydroxy, h) (C1-C6)alkoxy, i) (C1-C4)alkylthio, j) amino, k) cyano, l) nitro, m) mono-N— or di-N,N—(C1-C6)alkylamino, or n) —NH—(C1-C)alkylamino;
• or wherein W is CR7R8 wherein R7 and R8 are linked together to form a three to six membered fully saturated carbocyclic ring;
• A is a) mono-N— or di-N,N—(C1-C6)alkylamino, b) (C2-C6)alkanoylamino, c) (C1-C6)alkoxy, d) a partially or fully saturated or fully unsaturated three to eight membered ring optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen, or e) a bicyclic ring consisting of two fused partially or fully saturated or fully unsaturated three to six membered rings, taken independently;
• wherein the bicyclic ring optionally has one to four heteroatoms selected independently from oxygen, sulfur and nitrogen;
• and
• wherein the A ring is optionally mono-, di- or tri-substituted independently with a) oxo, b) carboxy, c) halo, d) (C1-C6)alkoxycarbonyl, e) (C1-C6)alkyl, f) (C2-C6)alkenyl, g) (C3-C7)cycloalkyl, h) (C3-C7)cycloalkyl(C1-C6)alkyl, i) hydroxy, j) (C1-C6)alkoxy, k) (C1-C4)alkylthio, l) (C1-C4)alkylsulfonyl, m) amino, n) cyano, o) nitro, or p) mono-N— or di-N,N—(C1-C6)alkylamino;
• wherein the (C1-C6)alkyl and (C1-C6)alkoxy substitutents on the A ring are also optionally mono-, di- or tri-substituted independently with a) halo, b) hydroxy, c) (C1-C4)alkyl optionally substituted with one to nine fluoro, d) (C3-C6)cycloalkyl, e) (C1-C6)alkoxy, f) amino, or g) mono-N— or di-N,N—(C1-C6)alkylamino;
• or wherein the A ring is optionally mono-substituted with a partially or fully saturated or fully unsaturated three to eight membered ring, optionally having one to four heteroatoms selected independently from oxygen, sulfur and nitrogen;
• also wherein this three to eight membered ring is optionally mono-, di- or tri-substituted independently with a) halo, b) hydroxy, c) (C1-C4)alkyl optionally substituted with one to nine fluoro, d) (C3-C6)cycloalkyl, e) (C1-C6)alkoxy, f) amino, g) mono-N— or di-N,N—(C1-C6)alkylamino, or h) (C1-C4)alkylthio;
• provided that:
• when V and Y are each methylene and m and n are each one forming a six-membered piperidinyl ring, this ring is substituted by the phenyl ring (designated as J) at other than the 4-position;
• and
• when E is carbonyl, W is a bond and X is -B-C(R1R2)-Z wherein R1 and R2 are each hydrogen, B is —O— or —N(H)—, and Z is —C(O)OH or —C(O)O—(C1-C4)alkyl, then one of F or G must be a) —(C1-C4)alkyl, b) (C3-C6)cycloalkyl, c) (C1-C4)alkoxy or d) (C1-C4)alkylthio.