Compounds and Methods for Treating Dyslipidemia

Abstract

Compounds of Formula I wherein n, q, Y, R 1 , R 2a , R 2b , R 3a , R 3b , R 4 , R 5 , and R 6 are as defined herein and their pharmaceutical compositions and methods of use are disclosed.

1 . A compound of Formula I 
       
         
           
           
               
               
           
         
       
       wherein
 n is 0, 1, 2, or 3; 
 q is 0, 1, 2, 3, or 4; 
 Y is a bond, C═O, or —S(O) t ; wherein t is 0, 1, or 2;
 R 1  is selected from a group consisting of: hydroxy, C 1 -C 6  alkyl, aryl, C 2 -C 6  alkenyl, C 1 -C 6  haloalkyl, C 1 -C 6  cyanoalkyl, C 1 -C 6  alkylheterocyclyl, C 3 -C 8  cycloalkyl, C 1 -C 6  alkylcycloalkyl; C 1 -C 6  alkylaryl, heterocyclyl, C 1 -C 6  hydroxyalkyl, C 1 -C 6  alkoxy, aryloxy, —OC 2 -C 6  alkenyl, —OC 1 -C 6  haloalkyl, —OC 1 -C 6  cyanoalkyl, —OC 1 -C 6  alkylheterocyclyl, —OC 3 -C 8  cycloalkyl, —OC 1 -C 6  alkylcycloalkyl, —NR 7 R 8 , —OC 1 -C 6  alkylaryl, —O— heterocyclyl, —OC 1 -C 6  alkylheterocyclyl, C 1 -C 6  alkyl-O—C(O)NR 7 R 8 , C 1 -C 6  alkyl-NR 7 C(O)NR 7 R 8 , and C 0 -C 6  alkylCOOR 11 ; provided that R 1  is not hydroxy when Y is —S(O) t ; and wherein each cycloalkyl, aryl and alkylheterocyclyl group is optionally substituted with 1 to 3 groups independently selected from oxo, hydroxy, halo, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkyl, C 1 -C 6  hydroxyalkyl, CONR 11 R 12 , —NR 11 SO 2 R 12 , —NR 11 COR 12 , CO—C 3  alkylNR 11 R 12 , C 1 -C 3  alkylCO 11 , C 0 -C 6  alkylCOOR 11 , cyano, C 1 -C 6  alkylcycloalkyl, phenyl, —OC 1 -C 6  alkylcycloalkyl, —OC 1 -C 6  alkylaryl, —OC 1 -C 6  alkylheterocyclyl, and C 1 -C 6  alkylaryl; 
 R 2a  and R 2b  are each independently selected from the group consisting of: hydrogen, hydroxy, halo, oxo, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkyl, CONR 11 R 12 , —NR 11 SO 2 R 12 , —NR 11 COR 12 , C 0 -C 6  alkylNR 11 R 12 , C 0 -C 6  alkylCO 11 , C 0 -C 6  alkylCOOR 11 , cyano, nitro, C 0 -C 6  alkylcycloalkyl, phenyl, C 0 -C 6  alkylaryl, heterocyclyl, C 3 -C 8  cycloalkyl, and C 1 -C 6  haloalkyl; provided that both R 2a  and R 2b  are not simultaneously hydrogen; 
 R 3a  and R 3b  are independently selected from the group consisting of: hydrogen, halo, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  alkoxy, and C 1 -C 6  haloalkyl; 
 R 4  is a group represented by the formula —NR 4a R 4b  where; 
 R 4a  is a heterocyclyl group substituted with 1 to 3 groups independently selected from C 3 -C 6  alkyl, C 3 -C 6  alkenyl, C 0 -C 6  cyanoalkyl, C 3 -C 6  alkoxy, C 1 -C 6  hydroxyalkyl, C 3 -C 6  haloalkyl, —OC(O)NR 11 R 12 , C 1 -C 6  alkylNR 11 R 12  wherein the C 1 -C 6  alkyl group is optionally substituted with —OR 10  or C(O)OR 10 , C 0 -C 6  alkylNR 11 SO 2 R 12 , C 0 -C 6  alkylC(O)NR 11 R 12 , C 0 -C 6  alkylNR 11 C(O)R 12 , C 0 -C 6  alkylNR 11 C(O)OR 12 , C 0 -C 6  alkylNR 11 CHR 10 CO 2 R 12 , C 0 -C 6  alkylC(O)OR 11 , C 0 -C 6  alkylSO 2 NR 11 R 12 , C 0 -C 6  alkylS(O) t R 11 , C 3 -C 8  cycloalkyl, C 1 -C 6  alkylcycloalkyl, and C 0 -C 6  alkylheterocyclyl wherein the heterocyclyl of the C 0 -C 6  alkylheterocyclyl group is optionally substituted with halo, C 1 -C 6  alkyl, oxo, —CO 2 R 11  and —NR 11 R 12 ; and 
 R 4b  is selected from the group consisting of C 1 -C 6  alkylaryl, C 2 -C 6  alkenylaryl, C 2 -C 6  alkynylaryl, C 1 -C 6  alkylheterocyclyl, C 2 -C 6  alkenylheterocyclyl, C 1 -C 6  alkylcycloalkyl, and C 1 -C 6  alkyl-O—C 1 -C 6  alkylaryl, wherein each cycloalkyl, aryl, or heterocyclic group is optionally substituted with 1-3 groups independently selected from the group consisting of hydroxy, oxo, —SC 1 -C 6  alkyl, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  haloalkyl, halogen, C 1 -C 6  alkoxy, aryloxy, C 2 -C 6  hydroxyalkenyl, C 1 -C 6  haloalkoxyalkyl, C 0 -C 6  alkylNR 11 R 12 , —OC 1 -C 6  alkylaryl, nitro, cyano, C 1 -C 6  halohydroxyalkyl, and C 1 -C 6  hydroxyalkyl; 
 R 5  is selected from a group consisting of: hydrogen, hydroxy, halo, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 1 -C 6  alkoxy, aryloxy, —OC 2 -C 6  alkenyl, —OC 1 -C 6  haloalkyl, C 1 -C 6  haloalkyl, C 3 -C 8  cycloalkyl, C 1 -C 6  alkylaryl, C 1 -C 6  alkylheterocyclyl, C 2 -C 6  alkenylaryl, C 2 -C 6  alkenylheterocyclyl, aryl, heterocyclyl, cyano, nitro, C 0 -C 6  alkylNR 7 R 8 , C 0 -C 6  alkylCOR 7 , C 0 -C 6  alkylCO 2 R 7 , C 0 -C 6  alkylCONR 7 R 8 , CONR 7 SO 2 R 8 , —NR 7 SO 2 R 8 , —NR 7 COR 8 , —N═CR 7 R 8 , OCONR 7 R 8 , —S(O) t R 7 , —SO 2 NR 7 R 8 , C 0 -C 5 CH 2 OH, —OC 1 -C 6  alkylheterocyclyl, and —OC 1 -C 6  alkylaryl wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl group or subgroup is optionally substituted with oxo, alkoxy, aryloxy; and wherein any two R 5  groups may combine to form an optionally substituted 5, 6, or 7-member fused ring with the phenyl ring (A-ring) to which they are attached, wherein the 5, 6, or 7-member fused ring is saturated, partially unsaturated, or fully unsaturated and optionally contains 1, 2, or 3 heteroatoms independently selected from O, N, and S; 
 R 6  is independently selected from a group consisting of hydrogen, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, hydroxy, COR 7 , C 1 -C 6  alkoxy, aryloxy, —OC 2 -C 6  alkenyl, —OC 1 -C 6  haloalkyl, C 1 -C 6  alkylNR 7 R 8 , C 3 -C 8  cycloalkyl, heterocyclyl, aryl, C 1 -C 6  alkyl-O—C(O)NR 7 R 8 , C 1 -C 6  alkyl-NR 7 C(O)NR 7 R 8  and C 1 -C 6  alkylcycloalkyl; 
 R 7  and R 8  are each independently selected from a group consisting of: hydrogen, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, —OC 1 -C 6  alkyl, C 1 -C 6  haloalkyl, —O-aryl, —OC 3 -C 8  cycloalkyl, —O— heterocyclyl, —NR 7 R 8 , —C 1 -C 6  alkylcycloalkyl, —OC 1 -C 6  alkylcycloalkyl, —OC 1 -C 6  alkylheterocyclyl, C 1 -C 6  alkylheterocyclyl, —OC 1 -C 6  alkylaryl, C 3 -C 8  cycloalkyl, heterocyclyl, aryl, and C 1 -C 6  alkylaryl, wherein each alkyl, cycloalkyl, heterocyclic or aryl group is optionally substituted with 1-3 groups independently selected from hydroxy, CN, halo, C 1 -C 6  alkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkyl, and NR 11 R 12 , or R 7  and R 8  combine to form a nitrogen containing heterocyclic ring having 0, 1, or 2 additional heteroatoms selected from oxygen, nitrogen and sulfur and wherein the nitrogen-containing heterocycle is optionally substituted with oxo, or C 1 -C 6  alkyl; 
 R 10 , R 11 , and R 12  are each independently selected from a group consisting of: hydrogen, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 3 -C 8  cycloalkyl, heterocyclyl, aryl, and C 1 -C 6  alkylaryl, wherein each alkyl, aryl, cycloalkyl, and heterocyclyl group is optionally substituted with 1-3 groups independently selected from halogen, C 1 -C 6  alkylheterocyclyl, and C 1 -C 6  haloalkyl, or R 11  and R 12  combine to form a nitrogen containing heterocyclic ring which may have 0, 1, or 2 additional heteroatoms selected from oxygen, nitrogen or sulfur and is optionally substituted with oxo, C 1 -C 6  alkyl, COR 7 , and —SO 2 R 7 ; 
 or a pharmaceutically acceptable salt, enantiomer, racemate, diastereomer or mixture of diastereomers thereof. 
 
 
     
     
         2 . A compound according to  claim 1  wherein n and q are independently 0 or 1. 
     
     
         3 . A compound according to  claim 1  or a pharmaceutically acceptable salt, enantiomer, diastereomer or mixture of diastereomers thereof, where n is 0, Y is C(O), and R 1  is selected from a group consisting of: hydroxy, —Oaryl, —OC 1 -C 6  haloalkyl, —OC 1 -C 6  alkylcycloalkyl, —OC 3 -C 8  cycloalkyl, —OC 1 -C 6  alkylcycloalkylNR 7 R 8 , —OC 1 -C 6  alkyl, —OC 1 -C 6  alkylaryl, —OC 1 -C 6  cyanoalkyl, —OC 3 -C 8  cycloalkylCO 2 R 11 , —OC 1 -C 6  alkylNR 7 R 8 , and —OC 1 -C 6  alkylheterocyclyl; and wherein each alkyl, cycloalkyl, aryl, or heterocyclyl is optionally substituted with 1 or 2 groups selected from halo, hydroxyl, C 1 -C 3  hydroxyalkyl, C 0 -C 3  alkylNR 11 R 12 , C 0 -C 3  alkylCOOH, CONH 2 , cyano, and CO—C 3  alkylC(O)OC 1 -C 3  alkyl. 
     
     
         4 . A compound according to  claim 1 , or a pharmaceutically acceptable salt, enantiomer, diastereomer or mixture of diastereomers thereof, wherein R 2  is C 3 -C 8  cycloalkyl or C 1 -C 6  alkyl. 
     
     
         5 . A compound according to  claim 1 , or a pharmaceutically acceptable salt, enantiomer, diastereomer or mixture of diastereomers thereof, wherein n is 0, Y is a bond, and R 1  is selected from a group consisting of: C 1 -C 6  alkyl, C 0 -C 6  alkylcycloalkyl, C 1 -C 6  alkylheterocyclyl, C 2 -C 6  haloalkyl, C 0 -C 6  alkylaryl, C 1 -C 6  alkylcycloalkylNR 7 R 8 , C 1 -C 6  cyanoalkyl, C 1 -C 6  alkylCO 2 R 11 , C 1 -C 6  alkylcycloalkylCO 2 R 11 , C 1 -C 6  hydroxyalkyl, and C 1 -C 6  alkylNR 7 R 8 ; and wherein each alkyl, cycloalkyl, aryl, or heterocyclyl is optionally substituted with 1 or 2 groups selected from halo, hydroxyl, C 1 -C 3  hydroxyalkyl, C 0 -C 3  alkylNR 11 R 12 , C 0 -C 3  alkylCOOH, and cyano. 
     
     
         6 . A compound according to  claim 1 , or a pharmaceutically acceptable salt, enantiomer, diastereomer or mixture of diastereomers thereof, wherein R 3a  and R 3b  are both hydrogen and R 4  is NR 4a R 4b ; wherein R 4b  is 3,5-bistrifluoromethylbenzyl and R 4a  is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       wherein, R is independently selected from the group consisting of: C 3 -C 6  alkyl, C 1 -C 6  hydroxyalkyl, C 3 -C 6  alkoxy, C 0 -C 6  alkylcycloalkyl, C 0 -C 6  alkylheterocyclyl, C 1 -C 6  cyanoalkyl, C 3 -C 6  haloalkyl, C 0 -C 6  alkylNR 11 R 12 , C 1 -C 6  alkylC(O)NR 11 R 12 , and C 1 -C 6  alkylC(O)OR 11 . 
     
     
         7 . A compound according to  claim 1  selected from the group consisting of: 
       (2R,4S)-4-[(3,5-bistrifluoromethylbenzyl)-(2-propyl-2H-tetrazol-5-yl)amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-[(3,5-bistrifluoromethylbenzyl)-(2-cyanomethyl-2H-tetrazol-5-yl)amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-((3,5-Bis-trifluoromethyl-benzyl)-{2-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-2H-tetrazol-5-yl}-amino)-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-{(3,5-bistrifluoromethylbenzyl)-[2-(2-amino-ethyl)-2H-tetrazol-5-yl)]amino}-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-[(3,5-bistrifluoromethylbenzyl)-(2-cyclopropylmethyl-2H-tetrazol-5-yl)amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-[(3,5-bistrifluoromethylbenzyl)-(2-methoxycarbonylmethyl-2H-tetrazol-5-yl)amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-[(3,5-bistrifluoromethylbenzyl)-(2-carboxymethyl-2H-tetrazol-5-yl)amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-[(3,5-bistrifluoromethylbenzyl)-(2-isopropyl-2H-tetrazol-5-yl)amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-[(3,5-bistrifluoromethylbenzyl)-(2-isobutyl-2H-tetrazol-5-yl)amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-[(3,5-bistrifluoromethylbenzyl)-(2-butyl-2H-tetrazol-5-yl)amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-[(3,5-bistrifluoromethylbenzyl)-(2-tert-butyl-2H-tetrazol-5-yl)amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-{(3,5-bistrifluoromethylbenzyl)-[2-(2-hydroxy-ethyl)-2H-tetrazol-5-yl)]amino}-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-{(3,5-bistrifluoromethylbenzyl)-[2-(3-hydroxy-propyl)-2H-tetrazol-5-yl)]amino}-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-{(3,5-bistrifluoromethylbenzyl)-[2-(2-chloro-ethyl)-2H-tetrazol-5-yl)]amino}-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-{(3,5-bistrifluoromethylbenzyl)-[2-(2-carbamoylmethyl)-2H-tetrazol-5-yl)]amino}-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-{(3,5-bistrifluoromethylbenzyl)-[2-(2-dimethylcarbamoylmethyl)-2H-tetrazol-5-yl)]amino}-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(2-cyano-ethyl)-2H-tetrazol-5-yl]-amino}-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-[[2-(3-Amino-propyl)-2H-tetrazol-5-yl]-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (+/−)-cis 4-[[2-(2-Amino-ethyl)-2H-tetrazol-5-yl]-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-cyclopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (+/−)-cis 4-[[2-(2-Amino-ethyl)-2H-tetrazol-5-yl]-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-propyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (+/−)-cis 4-[[2-(2-Amino-ethyl)-2H-tetrazol-5-yl]-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (+/−)-cis 4-[[2-(2-Amino-ethyl)-2H-tetrazol-5-yl]-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-isopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (+/−)-cis 4-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(3-hydroxy-propyl)-2H-tetrazol-5-yl]-amino}-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (+/−)-cis-4-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(3-hydroxy-propyl)-2H-tetrazol-5-yl]-amino}-2-isopropyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (+/−)-cis-4-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(3-methoxy-propyl)-2H-tetrazol-5-yl]-amino}-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (+/−)-cis-4-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(1-methyl-piperidin-4-yl)-2H-tetrazol-5-yl]-amino}-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (+/−)-cis-4-[[2-(2-Aziridin-1-yl-ethyl)-2H-tetrazol-5-yl]-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (+/−)-cis-4-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(2-pyrrolidin-1-yl-ethyl)-2H-tetrazol-5-yl]-amino}-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(1-methyl-pyrrolidin-3R-yl)-2H-tetrazol-5-yl]-amino}-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2S,4R)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(1-methyl-pyrrolidin-3R-yl)-2H-tetrazol-5-yl]-amino}-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(1-methyl-pyrrolidin-3S-yl)-2H-tetrazol-5-yl]-amino}-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2S,4R)-4-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(1-methyl-pyrrolidin-3S-yl)-2H-tetrazol-5-yl]-amino}-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (+/−)-cis-4-[(3,5-Bis-trifluoromethyl-benzyl)-(2-piperidin-4-yl-2H-tetrazol-5-yl)-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (+/−)-cis-4-[(2-Azetidin-3-yl-2H-tetrazol-5-yl)-(3,5-bis-trifluoromethyl-benzyl)-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-[(3,5-Bis-trifluoromethyl-benzyl)-(2-pyrrolidin-3R-yl-2H-tetrazol-5-yl)-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2S,4R)-4-[(3,5-Bis-trifluoromethyl-benzyl)-(2-pyrrolidin-3R-yl-2H-tetrazol-5-yl)-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-[(3,5-Bis-trifluoromethyl-benzyl)-(2-pyrrolidin-3S-yl-2H-tetrazol-5-yl)-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2S,4R)-4-[(3,5-Bis-trifluoromethyl-benzyl)-(2-pyrrolidin-3S-yl-2H-tetrazol-5-yl)-amino]-2-methyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester, 
       (2R,4S)-4-{(3,5-bistrifluoromethylbenzyl)-[2-(2-amino-ethyl)-2H-tetrazol-5-yl)]amino}-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid isopropyl ester methanesulfonic acid salt, and pharmaceutically acceptable salt, enantiomer, racemate, diastereomer or mixture of diastereomers thereof. 
     
     
         8 - 10 . (canceled) 
     
     
         11 . A method of treating atherosclerosis comprising administering a therapeutically effective composition comprising a compound of Formula I according to  claim 1 , or a pharmaceutically acceptable salt, enantiomer, racemate, diastereomer, or mixture of diastereomers thereof to a patient. 
     
     
         12 - 13 . (canceled) 
     
     
         14 . A pharmaceutical composition comprising a compound according to  claim 1 , or a pharmaceutically acceptable salt, enantiomer, racemate diastereomer, mixture of diastereomers thereof, to a patient in need thereof, and at least one of: a carrier, diluent and excipient. 
     
     
         15 - 16 . (canceled) 
     
     
         17 . A method of raising plasma HDL-cholesterol in a mammal comprising administering a therapeutically effective dose of a compound according to  claim 1 , or a pharmaceutically acceptable salt, enantiomer, racemate, diastereomer, or mixture of diastereomers thereof to said mammal. 
     
     
         18 . A method of treating coronary heart disease comprising administering a therapeutically effective composition comprising a compound of Formula I according to  claim 1 , or a pharmaceutically acceptable salt, enantiomer, racemate, diastereomer, or mixture of diastereomers thereof to a patient. 
     
     
         19 . A method according to  claim 18  wherein said treating coronary heart disease comprises treating dyslipidemia. 
     
     
         20 . A method according to  claim 19  comprising increasing plasma HDL-cholesterol in said patient. 
     
     
         21 . A method according to  claim 19  comprising decreasing plasma LDL-cholesterol in said patient. 
     
     
         22 . A method according to  claim 18  comprising raising the ratio of plasma HDL-cholesterol to plasma LDL-cholesterol in said patient. 
     
     
         23 . A pharmaceutical composition of  claim 14  comprising one or more cardio protective agents selected from the group consisting of: statins, leptin, and lipid regulating agents.