Ppar activators

Abstract

PPAR alpha activators, pharmaceutical compositions containing such compounds and the use of such compounds to elevate certain plasma lipid levels, including high density lipoprotein-cholesterol and to lower certain other plasma lipid levels, such as LDL-cholesterol and triglycerides and accordingly to treat diseases which are exacerbated by low levels of HDL cholesterol and/or high levels of LDL-cholesterol and triglycerides, such as atherosclerosis and cardiovascular diseases, in mammals, including humans.

1 . 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) (C 1 -C 4 )alkyl optionally substituted with one to nine fluoro, d) (C 3 -C 6 )cycloalkyl, e) hydroxy, f) (C 1 -C 4 )alkoxy or g) (C 1 -C 4 )alkylthio;  
       X is a) -Z or b) -B-C(R 1 R 2 )-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—(C 1 -C 4 )alkyl, c) —C(O)O—(C 0 -C 4 )alkyl-aryl, d) —C(O)—NH 2 , 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)SO 2 R 4 , or k) —NHSO 2 R 4 ; wherein R 4  is a) (C 1 -C 6 )alkyl, b) amino or c) mono-N— or di-N,N—(C 1 -C 6 )alkylamino, wherein the (C 1 -C 6 )alkyl substitutents in R 4  are optionally independently substituted with one to nine fluoro;  
       R 1  is a) H, b) (C 1 -C 4 )alkyl, or c) (C 3 -C 6 )cycloalkyl;  
       R 2  is a) H, b) (C 3 -C 6 )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 R 2  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 (C 1 -C 4 )alkoxy, and c) the carbon(s) is optionally mono-substituted with oxo; and  
       wherein the carbon(s) in the carbon chain in R 2  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) (C 2 -C 6 )alkenyl, c) (C 1 -C 6 ) alkyl, d) hydroxy, e) (C 1 -C 6 )alkoxy, f) (C 1 -C 4 )alkylthio, g) amino, h) nitro, i) cyano, j) oxo, k) carboxy, l) (C 1 -C 6 )alkyloxycarbonyl, or m) mono-N— or di-N,N—(C 1 -C 6 )alkylamino; wherein the (C 1 -C 6 )alkyl and (C 1 -C 6 )alkoxy substitutents on the Q ring is optionally mono-, di- or tri-substituted independently with a) halo, b) hydroxy, c) (C 1 -C 6 )alkoxy, d) (C 1 -C 4 )alkylthio, e) amino, f) nitro, g) cyano, h) oxo, i) carboxy, j) (C 1 -C 6 )alkyloxycarbonyl, or k) mono-N— or di-N,N—(C 1 -C 6 )alkylamino; wherein the (C 1 -C 6 )alkyl substitutent is on the Q ring is also optionally substituted with one to nine fluoro;  
       or wherein R 1  and R 2  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((C 1 -C 4 )alkyl)-, e) (C 2 -C 8 )alkenyl, f) oxy, g) —(C 1 -C 4 )alkyl-O—, h) —NH—(C 1 -C 4 )alkyl-, or i) —(C 1 -C 6 )alkyl-; wherein the (C 1 -C 6 )alkyl and the (C 2 -C 8 )alkenyl groups in W may optionally be mono- or di-substituted independently with a) oxo, b) halo, c) (C 1 -C 6 )alkoxycarbonyl, d) (C 1 -C 6 )alkyl, e) (C 2 -C 6 )alkenyl, f) (C 3 -C 7 )cycloalkyl, g) hydroxy, h) (C 1 -C 6 )alkoxy, i) (C 1 -C 4 )alkylthio, j) amino, k) cyano, l) nitro, m) mono-N— or di-N,N—(C 1 -C 6 )alkylamino, or n) —NH—(C 1 -C)alkylamino;  
       or wherein W is CR 7 R 8  wherein R 7  and R 8  are linked together to form a three to six membered fully saturated carbocyclic ring;  
       A is a) mono-N— or di-N,N—(C 1 -C 6 )alkylamino, b) (C 2 -C 6 )alkanoylamino, c) (C 1 -C 6 )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) (C 1 -C 6 )alkoxycarbonyl, e) (C 1 -C 6 )alkyl, f) (C 2 -C 6 )alkenyl, g) (C 3 -C 7 )cycloalkyl, h) (C 3 -C 7 )cycloalkyl(C 1 -C 6 )alkyl, i) hydroxy, j) (C 1 -C 6 )alkoxy, k) (C 1 -C 4 )alkylthio, l) (C 1 -C 4 )alkylsulfonyl, m) amino, n) cyano, o) nitro, or p) mono-N— or di-N,N—(C 1 -C 6 )alkylamino; wherein the (C 1 -C 6 )alkyl and (C 1 -C 6 )alkoxy substitutents on the A ring are also optionally mono-, di- or tri-substituted independently with a) halo, b) hydroxy, c) (C 1 -C 4 )alkyl optionally substituted with one to nine fluoro, d) (C 3 -C 6 )cycloalkyl, e) (C 1 -C 6 )alkoxy, f) amino, or g) mono-N— or di-N,N—(C 1 -C 6 )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) (C 1 -C 4 )alkyl optionally substituted with one to nine fluoro, d) (C 3 -C 6 )cycloalkyl, e) (C 1 -C 6 )alkoxy, f) amino, g) mono-N— or di-N,N—(C 1 -C 6 )alkylamino, or h) (C 1 -C 4 )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(R 1 R 2 )-Z wherein R 1  and R 2  are each hydrogen, B is —O— or —N(H)—, and Z is —C(O)OH or —C(O)O—(C 1 -C 4 )alkyl, then one of F or G must be a) —(C 1 -C 4 )alkyl, b) (C 3 -C 6 )cycloalkyl, c) (C 1 -C 4 )alkoxy or d) (C 1 -C 4 )alkylthio.  
     
   
   
       2 . A compound of  claim 1  further provided that: 
 when E is carbonyl, W is a bond, X is -Z, and Z is —C(O)OH, —C(O)O—(C 1 -C 4 )alkyl, —C(O)NH 2 , then one of F or G must be a) —(C 1 -C 4 )alkyl, b) (C 3 -C 6 )cycloalkyl, c) (C 1 -C 4 )alkoxy or d) (C 1 -C 4 )alkylthio.    
   
   
       3 . A compound of  claim 1  wherein: 
 V and Y are each methylene or one of V and Y is carbonyl and the other is methylene;    E is carbonyl;    W is a) a bond, b) oxy, c) —N(H)—, d) —N(H)—(C 1 -C 4 )alkyl-, e) —(C 1 -C 4 )alkyl-, f) —(C 1 -C 4 )alkyl-O— or g) —CR 7 R 8 — wherein R 7  and R 8  are linked together to form a three-membered fully saturated carbocyclic ring; and    A 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;    wherein the A ring is optionally mono-, di- or tri-substituted independently with a) oxo, b) carboxy, c) halo, d) (C 1 -C 6 )alkoxycarbonyl, e) (C 1 -C 6 )alkyl, f) (C 2 -C 6 )alkenyl, g) (C 3 -C 7 )cycloalkyl, h) (C 3 -C 7 )cycloalkyl(C 1 -C 6 )alkyl, i) hydroxy, j) (C 1 -C 6 )alkoxy, k) (C 1 -C 4 )alkylthio, l) (C 1 -C 4 )alkylsulfonyl, m) amino, n) cyano, o) nitro, or p) mono-N— or di-N,N—(C 1 -C 6 )alkylamino; wherein the (C 1 -C 6 )alkyl and (C 1 -C 6 )alkoxy substitutents on the A ring are also optionally mono-, di- or tri-substituted independently with a) halo, b) hydroxy, c) (C 1 -C 4 )alkyl optionally substituted with one to nine fluoro, d) (C 3 -C 6 )cycloalkyl, e) (C 1 -C 6 )alkoxy, f) amino, or g) mono-N— or di-N,N—(C 1 -C 6 )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) (C 1 -C 6 )alkyl optionally substituted with one to nine fluoro, d) (C 3 -C 7 )cycloalkyl, e) (C 1 -C 6 )alkoxy optionally substituted with one to nine fluoro, f) amino, g) mono-N— or di-N,N—(C 1 -C 6 )alkylamino, or h) (C 1 -C 4 )alkylthio;    
   
   
       4 . A compound of  claim 3  wherein 
 A is a) phenyl optionally independently substituted with one or two 1) —(C 1 -C 6 )alkyl, 2) —CF 3 , 3) —OCF 3  4) —(C 1 -C 6 )alkoxy, 5) (C 3 -C 7 )cycloalkyl, 6) halo or 7) hydroxy; or b) thiazolyl optionally independently substituted with 1) one or two methyl or 2) phenyl optionally independently substituted with one or two a) —(C 1 -C 6 )alkyl, b) —CF 3 , c) —OCF 3 , d) —(C 1 -C 6 )alkoxy, e) (C 3 -C 7 )cycloalkyl, f) halo, g) —(C 1 -C 4 )alkylthio or h) hydroxy;    F and G are each independently a) hydrogen, b) halo, c) (C 1 -C 4 )alkyl or d) (C 1 -C 4 )alkoxy;    X is a) -Z or b) -B-C(R 1 R 2 )-Z;    B is a) oxy, b) thio or c) —N(H)—;    Z is a) —C(O)OH, b) —C(O)O—(C 1 -C 4 )alkyl, c) —C(O)NH 2  or d) tetrazolyl;    R 1  is a) hydrogen or b) methyl; and    R 2  is a) hydrogen or b) 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;    wherein the carbon(s) in the carbon chain in R 2  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.    
   
   
       5 . A compound of  claim 4  wherein 
 R 1  is a) hydrogen or b) methyl;    R 2  is a) hydrogen, b) methyl or c) —O—CH 2 -phenyl;    m is one, n is one and V and Y are each methylene to form a piperidinyl ring;    X is -B-C(R 1 R 2 )-Z;    B is oxy; and    the phenyl ring (designated as J) is attached at the 3-position of the piperidinyl ring.    
   
   
       6 . A compound of  claim 5  of the formula I-A or formula I-C  
     
       
         
         
             
             
         
       
       wherein R 1  and R 2  are each independently a) hydrogen or b) methyl;  
       F and G are each independently a) hydrogen or b) methyl; and  
       Z is —C(O)OH.  
     
   
   
       7 . A compound of  claim 6  wherein 
 W is a) oxy, b) —N(H)—, c) —N(H)—(C 1 -C 4 )alkyl-, d) —(C 1 -C 4 )alkyl- or e) —C 1 -C 4 )alkyl-O—; and A is phenyl optionally substituted with a) —(C 1 -C 4 )alkyl, b) —CF 3 , c) —OCF 3  d) —(C 1 -C 4 )alkoxy, e) cyclopropyl, f) halo, g) —(C 1 -C 4 )alkylthio or h) hydroxy; or    W is a bond; and A is thiazolyl optionally substituted with a) one or two -methyl, or b) -phenyl optionally substituted with 1) —(C 1 -C 4 )alkyl, 2) —CF 3 , 3) —OCF 3  4) —(C 1 -C 4 )alkoxy, 5) cyclopropyl, 6) halo or 7) —(C 1 -C 4 )alkylthio.    
   
   
       8 . A compound of  claim 4  wherein 
 m is one, n is one and V and Y are each methylene to form a piperidinyl ring;    X is -Z;    and    the phenyl ring (designated as J) is attached at the 3-position of the piperidinyl ring.    
   
   
       9 . A compound of  claim 8  of the formula I-B or formula I-D  
     
       
         
         
             
             
         
       
       wherein F and G are each a) hydrogen, b) methyl, c) fluoro or d) methoxy;  
       and  
       Z is a) —C(O)OH, b) —C(O)O—(C 1 -C 4 )alkyl or c) —C(O)NH 2 .  
     
   
   
       10 . A compound of  claim 9  wherein 
 W is a) —(C 1 -C 4 )alkyl- or b) —(C 1 -C 4 )alkyl-O—; and A is phenyl optionally substituted with a) —(C 1 -C 4 )alkyl, b) —CF 3 , c) —OCF 3 , d) —(C 1 -C 4 )alkoxy, e) cyclopropyl, f) halo, g) —(C 1 -C 4 )alkylthio, or h) hydroxy; or    W is a bond; and A is a) thiazolyl optionally substituted with 1) one or two -methyl or 2)-phenyl optionally substituted with i) —(C 1 -C 4 )alkyl, ii) —CF 3 , iii) —OCF 3  iv) —(C 1 -C 4 )alkoxy, v) cyclopropyl or vi) halo; or b) phenyl optionally substituted with 1) —(C 1 -C 4 )alkyl, 2) —CF 3 , 3)—OCF 3  4) —(C 1 -C 4 )alkoxy, 5) cyclopropyl, 6) halo, or 7) —(C 1 -C 4 )alkylthio.    
   
   
       11 . A compound of  claim 7  selected from: 
 2-{3-[1-(4-Isopropyl-phenylcarbamoyl)-piperidin-3-yl]-phenoxy}-2-methyl-propionic acid;    (S)-2-{3-[1-(4-Isopropyl-phenylcarbamoyl)-piperidin-3-yl]-phenoxy}-2-methyl-propionic acid;    (R)-2-{3-[1-(4-Isopropyl-phenylcarbamoyl)-piperidin-3-yl]-phenoxy}-2-methyl-propionic acid;    2-Methyl-2-(3-{1-[(4-trifluoromethyl-phenyl)-acetyl]-piperidin-3-yl}-phenoxy)-propionic acid;    (S)-2-Methyl-2-(3-{1-[(4-trifluoromethyl-phenyl)-acetyl]-piperidin-3-yl}-phenoxy)-propionic acid;    (R)-2-Methyl-2-(3-{1-[(4-trifluoromethyl-phenyl)-acetyl]-piperidin-3-yl}-phenoxy)-propionic acid.    2-(3-{1-[(4-Isopropyl-phenyl)-acetyl]-piperidin-3-yl}-phenoxy)-2-methyl-propionic acid;    (S)-2-(3-{1-[(4-Isopropyl-phenyl)-acetyl]-piperidin-3-yl}-phenoxy)-2-methyl-propionic acid;    (R)-2-(3-{1-[(4-Isopropyl-phenyl)-acetyl]-piperidin-3-yl}-phenoxy)-2-methyl-propionic acid;    2-(3-{1-[3-(4-Isopropyl-phenyl)-propionyl]-piperidin-3-yl}-phenoxy)-2-methyl-propionic acid;    (S)-2-(3-{1-[3-(4-Isopropyl-phenyl)-propionyl]-piperidin-3-yl}-phenoxy)-2-methyl-propionic acid;    (R)-2-(3-{1-[3-(4-Isopropyl-phenyl)-propionyl]-piperidin-3-yl}-phenoxy)-2-methyl-propionic acid;    2-(3-{1-[(4-Isopropyl-phenoxy)-acetyl]-piperidin-3-yl}-phenoxy)-2-methyl-propionic acid;    (S)-2-(3-{1-[(4-Isopropyl-phenoxy)-acetyl]-piperidin-3-yl}-phenoxy)-2-methyl-propionic acid; and    (R)-2-(3-{1-[(4-Isopropyl-phenoxy)-acetyl]-piperidin-3-yl}-phenoxy)-2-methyl-propionic acid;    2-(3-{1-[2-(4-Isopropyl-phenoxy)-2-methyl-propionyl]-piperidin-3-yl}-phenoxy)-2-methyl-propionic acid;    (S)-2-(3-{1-[2-(4-Isopropyl-phenoxy)-2-methyl-propionyl]-piperidin-3-yl}-phenoxy)-2-methyl-propionic acid;    (R)-2-(3-{1-[2-(4-Isopropyl-phenoxy)-2-methyl-propionyl]-piperidin-3-yl}-phenoxy)-2-methyl-propionic acid;    2-Methyl-2-(3-{1-[3-(4-trifluoromethyl-phenyl)-propionyl]-piperidin-3-yl}-phenoxy)-propionic acid;    (S)-2-Methyl-2-(3-{1-[3-(4-trifluoromethyl-phenyl)-propionyl]-piperidin-3-yl}-phenoxy)-propionic acid;    (R)-2-Methyl-2-(3-{1-[3-(4-trifluoromethyl-phenyl)-propionyl]-piperidin-3-yl}-phenoxy)-propionic acid;    2-Methyl-2-(3-{1-[(4-trifluoromethoxy-phenoxy)-acetyl]-piperidin-3-yl}-phenoxy)-propionic acid;    (S)-2-Methyl-2-(3-{1-[(4-trifluoromethoxy-phenoxy)-acetyl]-piperidin-3-yl}-phenoxy)-propionic acid;    (R)-2-Methyl-2-(3-{1-[(4-trifluoromethoxy-phenoxy)-acetyl]-piperidin-3-yl}-phenoxy)-propionic acid;    (3-{1-[(4-Isopropyl-phenyl)-acetyl]-piperidin-3-yl}-phenoxy)-acetic acid;    (S)-(3-{1-[(4-Isopropyl-phenyl)-acetyl]-piperidin-3-yl}-phenoxy)-acetic acid;    (R)-(3-{1-[(4-Isopropyl-phenyl)-acetyl]-piperidin-3-yl}-phenoxy)-acetic acid;    3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-phenyl ester;    (S)-3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-phenyl ester;    (R)-3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-phenyl ester;    (S)-2-(3-{1-[(4-tert-Butyl-phenyl)-acetyl]-piperidin-3-yl}-phenoxy)-2-methyl-propionic acid;    (R)-2-(3-{1-[(4-tert-Butyl-phenyl)-acetyl]-piperidin-3-yl}-phenoxy)-2-methyl-propionic acid;    2-(3-{1-[(4-tert-Butyl-phenyl)-acetyl]-piperidin-3-yl}-phenoxy)-2-methyl-propionic acid;    (S)-2-Methyl-2-(3-{1-[(4-trifluoromethoxy-phenyl)-acetyl]-piperidin-3-yl}-phenoxy)-propionic acid;    (R)-2-Methyl-2-(3-{1-[(4-trifluoromethoxy-phenyl)-acetyl]-piperidin-3-yl}-phenoxy)-propionic acid;    2-Methyl-2-(3-{1-[(4-trifluoromethoxy-phenyl)-acetyl]-piperidin-3-yl}-phenoxy)-propionic acid;    (S)-3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-benzyl ester;    (R)-3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-benzyl ester;    3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-benzyl ester;    (S)-3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-phenyl ester;    (R)-3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-phenyl ester;    3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-isopropyl-phenyl ester;    2-{3-[1-(4-Isopropyl-benzylcarbamoyl)-piperidin-3-yl]-phenoxy}-2-methyl-propionic acid;    (S)-2-{3-[1-(4-Isopropyl-benzylcarbamoyl)-piperidin-3-yl]-phenoxy}-2-methyl-propionic acid;    (R)-2-{3-[1-(4-Isopropyl-benzylcarbamoyl)-piperidin-3-yl]-phenoxy}-2-methyl-propionic acid;    3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester;    (S)-3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester;    (R)-3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester;    (S)-2-Methyl-2-{3-[1-(4-trifluoromethoxy-benzylcarbamoyl)-piperidin-3-yl]-phenoxy}-propionic acid;    (R)-2-Methyl-2-{3-[1-(4-trifluoromethoxy-benzylcarbamoyl)-piperidin-3-yl]-phenoxy}-propionic acid;    2-Methyl-2-{3-[1-(4-trifluoromethoxy-benzylcarbamoyl)-piperidin-3-yl]-phenoxy}-propionic acid;    3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-cyclopropyl-benzyl ester;    (S)-3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-cyclopropyl-benzyl ester;    (R)-3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-cyclopropyl-benzyl ester;    (S)-3-(3-carboxymethoxy-4-methyl-phenyl)-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester;    (R)-3-(3-carboxymethoxy-4-methyl-phenyl)-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester;    3-(3-carboxymethoxy-4-methyl-phenyl)-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester;    (S)-3-[3-(1-Carboxy-1-methyl-ethoxy)-4-methyl-phenyl]-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester;    (R)-3-[3-(1-Carboxy-1-methyl-ethoxy)-4-methyl-phenyl]-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester;    3-[3-(1-Carboxy-1-methyl-ethoxy)-4-methyl-phenyl]-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester;    (S)-2-Methyl-2-(3-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-phenoxy)-propionic acid;    (R)-2-Methyl-2-(3-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-phenoxy)-propionic acid;    2-Methyl-2-(3-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-phenoxy)-propionic acid;    (S)-(2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-phenoxy)-acetic acid;    (R)-(2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-phenoxy)-acetic acid;    (2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-phenoxy)-acetic acid;    (S)-2-Methyl-2-(2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-phenoxy)-propionic acid;    (R)-2-Methyl-2-(2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-phenoxy)-propionic acid;    2-Methyl-2-(2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-phenoxy)-propionic acid;    (R)-3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 3-trifluoromethyl-benzyl ester; 
 (S)-3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 3-trifluoromethyl-benzyl ester;  
   3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 3-trifluoromethyl-benzyl ester;    (S)-3-[3-(1-Carboxy-1-methyl-ethoxy)-4-methyl-phenyl]-piperidine-1-carboxylic acid 2-(4-trifluoromethyl-phenyl)-ethyl ester;    (R)-3-[3-(1-Carboxy-1-methyl-ethoxy)-4-methyl-phenyl]-piperidine-1-carboxylic acid 2-(4-trifluoromethyl-phenyl)-ethyl ester; and    3-[3-(1-Carboxy-1-methyl-ethoxy)-4-methyl-phenyl]-piperidine-1-carboxylic acid 2-(4-trifluoromethyl-phenyl)-ethyl ester.    
   
   
       12 . A compound of  claim 10  selected from: 
 2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid;    (S)-2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid;    (R)-2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid;    3-(3-carboxy-4-methyl-phenyl)-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester;    (S)-3-(3-carboxy-4-methyl-phenyl)-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester;    (R)-3-(3-carboxy-4-methyl-phenyl)-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester;    (R)-2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid;    (S)-2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid;    2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid;    (S)-2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid;    (R)-2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid;    2-methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid;    (R)-3-(3-carboxy-4-methyl-phenyl)-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester;    (S)-3-(3-carboxy-4-methyl-phenyl)-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester;    3-(3-carboxy-4-methyl-phenyl)-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester;    2-Methoxy-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid;    (S)-2-Methoxy-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid;    (R)-2-Methoxy-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid;    2-Fluoro-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid;    (S)-2-Fluoro-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid;    (R)-2-Fluoro-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzoic acid;    2-Methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzamide;    (S)-2-Methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzamide;    (R)-2-Methyl-5-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazole-5-carbonyl]-piperidin-3-yl}-benzamide;    (R)-3-(3-Carboxy-4-methyl-phenyl)-piperidine-1-carboxylic acid 2-(4-trifluoromethyl-phenyl)-ethyl ester;    (S)-3-(3-Carboxy-4-methyl-phenyl)-piperidine-1-carboxylic acid 2-(4-trifluoromethyl-phenyl)-ethyl ester; and    3-(3-Carboxy-4-methyl-phenyl)-piperidine-1-carboxylic acid 2-(4-trifluoromethyl-phenyl)-ethyl ester.    
   
   
       13 . A method for treating obesity, overweight condition, hypertriglyceridemia, hyperlipidemia, hypoalphalipoproteinemia, metabolic syndrome, diabetes mellitus (Type I and/or Type II), hyperinsulinemia, impaired glucose tolerance, insulin resistance, diabetic complications, atherosclerosis, hypertension, coronary heart disease, hypercholesterolemia, inflammation, osteoporosis, thrombosis or congestive heart failure in a mammal by administering to a mammal in need of such treatment a therapeutically effective amount of a compound of  claim 1 , a prodrug thereof, or a pharmaceutically acceptable salt of said compound or of said prodrug.  
   
   
       14 . A pharmaceutical composition which comprises a therapeutically effective amount of a compound of  claim 1 , a prodrug thereof, or a pharmaceutically acceptable salt of said compound or of said prodrug and a pharmaceutically acceptable carrier, vehicle or diluent.  
   
   
       15 . A kit comprising: 
 a. a first compound, said first compound being a compound of  claim 1 , a prodrug thereof, or a pharmaceutically acceptable salt of said compound or of said prodrug and a pharmaceutically acceptable carrier, vehicle or diluent in a first unit dosage form;    b. a second compound, said second compound being a lipase inhibitor, an HMG-CoA reductase inhibitor, an HMG-CoA synthase inhibitor, an HMG-CoA reductase gene expression inhibitor, an HMG-CoA synthase gene expression inhibitor, an MTP/Apo B secretion inhibitor, a CETP inhibitor, a bile acid absorption inhibitor, a cholesterol absorption inhibitor, a cholesterol synthesis inhibitor, a squalene synthetase inhibitor, a squalene epoxidase inhibitor, a squalene cyclase inhibitor, a combined squalene epoxidase/squalene cyclase inhibitor, a fibrate, niacin, a combination of niacin and lovastatin, an ion-exchange resin, an antioxidant, an ACAT inhibitor or a bile acid sequestrant and a pharmaceutically acceptable carrier, vehicle or diluent in a second unit dosage form; and    c. means for containing said first and second dosage forms    wherein the amounts of first and second compounds result in a therapeutic effect.