Compounds and Methods for Treating Dyslipidemia

Abstract

Compounds of Formula (I): wherein n, m, p, q, Y, R1, R2, R3a, R3b, R4, R5, and R6 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; 
       m is 0, 1, 2, or 3; 
       p is 1 or 2; 
       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  alkylheterocyclic, C 3 -C 8  cycloalkyl, C 1 -C 6  alkylcycloalkyl; C 1 -C 6  alkylaryl, heterocyclyl, C 1 -C 6  alkylalcohol, C 1 -C 6  alkoxy, aryloxy, —OC 2 -C 6  alkenyl, —OC 1 -C 6  haloalkyl, —OC 1 -C 6  alkylheterocyclic, —OC 3 -C 8  cycloalkyl, —OC 1 -C 6  alkylcycloalkyl, —NR 7 R 8  and —OC 1 -C 6  alkylaryl, —O-heterocyclic, —OC 1 -C 6  alkylheterocyclic, C I -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 heterocyclic group is optionally substituted with 1 to 3 groups independently selected from oxo, hydroxy, halogen, 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  alkylalcohol, CONR 11 R 12 , NR 11 SO 2 R 12 , NR 11 COR 12 , C 0 -C 3  alkylNR 11 R 12 , C 1 -C 3  alkylCOR 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  alkylheterocyclic, and C 1 -C 6  alkylaryl; 
 each R 2  is bound only to a carbon atom and is a group independently selected from the group consisting of: hydrogen, hydroxy, halogen, oxo, C 2 -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  alkylCOR 1 , 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; and wherein two independently selected R 2  groups are optionally gem-disubstituted; 
 R 3a  and R 3b  are independently selected from the group consisting of: hydrogen, halogen, 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  wherein; 
 R 4a  is a heterocyclic, C 1 -C 6  alkylheterocyclic, or C 2 -C 6  alkenylheterocyclic group wherein each heterocyclic group is optionally substituted with 1 to 3 groups independently selected from the group consisting of: oxo, hydroxyl, halogen, —NR 11 R 12 , C 1 -C 6  alkyl, C 1 -C 6  alkenyl, C 0 -C 6  alkylCN, C 1 -C 6  alkoxy, C 1 -C 6  alkylalcohol, C 1 -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  alkylNO 2 , 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 C(O)NR 10 R 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  alkylheterocyclic wherein the heterocycle of the C 0 -C 6  alkylheterocyclic 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  alkylheterocyclic, C 2 -C 6  alkenylheterocyclic, C 1 -C 6  alkylcycloalkyl, 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 1 -C 6  alkenyl, C 1 -C 6  alkynyl, C 1 -C 6  haloalkyl, halogen, C 1 -C 6  alkoxy, aryloxy, C 1 -C 6  alkenyloxy, C 1 -C 6  haloalkoxyalkyl, C 0 -C 6  alkylNR 11 R 12 , —OC 1 -C 6  alkylaryl, nitro, cyano, C 1 -C 6  haloalkylalcohol, and C 1 -C 6  alkyl alcohol;
 R 5  is selected from a group consisting of: hydrogen, hydroxy, halogen, 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  alkylheterocyclic, C 2 -C 6  alkenylaryl, C 2 -C 6  alkenylheterocyclic, aryl, heterocyclic, 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  alkylheterocyclic, and —OC 1 -C 6  alkylaryl wherein each of the alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heterocyclic group or subgroup is optionally substituted with oxo, alkyloxy, 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, heterocyclic, 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-heterocyclic, —NR 7 R 8 , —C 1 -C 6  alkylcycloalkyl, —OC 1 -C 6  alkylcycloalkyl, —OC 1 -C 6  alkylheterocyclic, C 1 -C 6  alkylheterocyclic, —O C 1 -C 6  alkylaryl, C 3 -C 8  cycloalkyl, heterocyclic, 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, halogen, 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 which 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 independently selected from a group consisting of hydrogen, C 1 -C 6  alkyl, C 1 -C 6  alkenyl, C 3 -C 8  cycloalkyl, heterocyclic, aryl, C 1 -C 6  alkylaryl, wherein each alkyl, aryl, cycloalkyl, and heterocyclic group is optionally substituted with 1-3 groups independently selected from halogen, C 1 -C 6  alkylheterocyclic, 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, solvate, enantiomer, racemate, diastereomer or mixture of diastereomers thereof. 
 
     
   
   
       2 . A compound of  claim 1  wherein p is 1. 
   
   
       3 . A compound according to  claim 1  wherein n, m, and q are independently 0, or 1. 
   
   
       4 . A compound according to  claim 1  wherein p is 1, n is 0, Y is C(O), and R 1  is selected from a group consisting of: hydroxy, hydrogen, C 1 -C 6  alkyl, C 0 -C 6  alkylcycloalkyl, C 0 -C 6  alkylheterocyclic, C 1 -C 6  haloalkyl, C 0 -C 6  alkylaryl, —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 0 -C 6  alkylaryl, —OC 1 -C 6  alkylcyano, —OC 1 -C 6  alkylCO 2 R 11 , —OC 3 -C 8  cycloalkylCO 2 R 11 , —OC 1 -C 6  alkylhydroxy, —OC 1 -C 6  alkylNR 7 R 8  and —OC 1 -C 6  alkylheterocyclic; and wherein each alkyl, cycloalkyl, aryl, or heterocyclic is optionally substituted with 1 or 2 groups selected from halogen, C 0 -C 3  alkylalcohol, C 0 -C 3  alkylamine, C 0 -C 3  alkylCOOH, C 0 -C 3  alkylCONH 2 , C 0 -C 3  alkylcyano, and
 C 0 -C 3  alkylC(O)OC 1 -C 3  alkyl.   
   
   
       5 . A compound according to  claim 1  wherein p is 1, 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  alkylheterocyclic, C 2 -C 6  haloalkyl, C 0 -C 6  alkylaryl, C 1 -C 6  alkylcycloalkylNR 7 R 8 , C 1 -C 6  alkylcyano, C 1 -C 6  alkylCO 2 R 11 , C 1 -C 6  alkylcycloalkylCO 2 R 11 , C 1 -C 6  alkylalcohol, and C 1 -C 6  alkylNR 7 R 8 ; and wherein each alkyl, cycloalkyl, aryl, or heterocyclic is optionally substituted with 1 or 2 groups selected from halogen, C 0 -C 3  alkylalcohol, C 0 -C 3  alkylamine, C 0 -C 3  alkylCOOH, C 0 -C 3  alkylCONH 2 , and C 0 -C 3  alkylcyano. 
   
   
       6 . A compound compound according to  claim 1  wherein p is 1, 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 each R is independently selected from the group consisting of: halogen, C 0 -C 6  alkylalcohol, hydrogen, C 1 -C 6  alkyl, C 1 -C 6  alkoxy C 0 -C 6  alkylcycloalkyl, C 0 -C6 alkylheterocyclic, C 1 -C 6  alkylCN, C 1 -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 selected from the group consisting of:
 (S)-5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid tetrahydro-pyran-4-yl ester,   (S)-2-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(1-cyclopentylmethyl-7-methyl-8-trifluoromethyl-2,3,4, 5-tetrahydro-1H-benzo[b]azepin-5-yl)-amino]-tetrazol-2-yl}-ethanol,   (S)-2-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-yl}-ethanol,   (+/−)-9-[(3,5-Bis-trifluoromethyl-benzyl)-(2H-tetrazol-5-yl)-amino]-2,2-difluoro-6,7,8,9-tetrahydro-1,3-dioxa-5-aza-cyclohepta[f]indene-5-carboxylic acid isopropyl ester,   (+/−)-Isopropyl 5-[(3,5-bistrifluoromethyl-benzyl)-(1H-tetrazol-5-yl)-amino]-8-chloro-2,3,4, 5-tetrahydrobenzo[b]azepine-1-carboxylate,   (+/−)-isopropyl 5-[(3,5-bistrifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate,   (+/−) isopropyl -6-[(3,5-bistrifluoromethyl-benzyl)-(1H-tetrazol-5-yl)-amino]-2,3,6,7,8,9-hexahydro-1H-10-aza-cyclohepta[e]indene-10-carboxylate,   (+/−)-isopropyl 5-[(3,5-bistrifluoromethyl-benzyl)-(5-methyl-1H-pyrazol-3-yl)-amino]-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate,   +/−)-isopropyl 5-[(3,5-bistrifluoromethyl-benzyl)-(5-methyl-isoxazol-5-yl)-amino]-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate,)   (S)-6-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-21 - 1-tetrazol-5-yl)-amino]-4-methyl-2,3,6,7,8,9-hexahydro-1H-10-aza-cyclohepta[e]indene-10-carboxylic acid isopropyl ester,   (S)-isopropyl 5-[(3,5-bistrifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-8,9-dimethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate,   (S)-isopropyl 5-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(2-hydroxy-ethyl)-2H-tetrazol-5-yl]-amino}-8,9-dimethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate,   (S)-9-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-2,3,6,7,8,9-hexahydro-1H-5-aza-cyclohepta[f]indene-5-carboxylic acid tert-butyl ester,   (S)-(3,5-Bis-trifluoromethyl-benzyl)-(5-cyclopentylmethyl-1,2,3,5,6,7,8,9-octahydro-5-aza-cyclohepta[f]inden-9-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,   (S)-(3,5-Bis-trifluoromethyl-benzyl)-(5-cyclopentylmethyl-3,5,6,7,8,9-hexahydro-1H-2-oxa-5-aza-cyclohepta[f]inden-9-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,   (S)-5-{9-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-1,3,6,7,8,9-hexahydro-2-oxa-5-aza-cyclohepta[f]inden-5-yl)-3,3-dimethyl-pentanoic acid,   (S)-5-(9-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(2-hydroxy-ethyl)-2H-tetrazol-5-yl]-amino}-1,3,6,7,8,9-hexahydro-2-oxa-5-aza-cyclohepta[f]inden-5-yl)-3,3-dimethyl-pentanoic acid,   (3,5-Bis-trifluoromethyl-benzyl)-(1-cyclopentylmethyl-2,3,4,5,7,8,9,10-octahydro-1H-naphtho[2,3-b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,   (S)-6-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(2-hydroxy-ethyl)-2H-tetrazol-5-yl]-amino)-2,3,6,7,8,9-hexahydro-1H-10-aza-cyclohepta[e]indene-10-carboxylic acid isopropyl ester,   (S)-6-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(2-hydroxy-ethyl)-2H-tetrazol-5-yl]-amino}-4-methyl-2,3,6,7,8,9-hexahydro-1H-10-aza-cyclohepta[e]indene-10-carboxylic acid isopropyl ester,   (S)-9-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-2,3,6,7,8,9-hexahydro-1H-5-aza-cyclohepta[f]indene-5,carboxylic acid 2-carboxy-2-methyl-propyl ester,   (S)-1-{5-[(3,5-Bis-trifluoromethyl-benzyl)-2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-yl)-3-furan-2-ylmethoxy)-propan-2-one,   2-{5-[(3,5-Bis-trifluoromethyl-benzyl)-2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-yl}-1-phenyl-ethanol,   2-{5-[(3,5-Bis-trifluoromethyl-benzyl)-2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-yl) -2-phenyl-ethanol,   (4-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(3-methyl-isoxazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-cyclohexyl)-acetic acid methyl ester,   (4-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(3-methyl-isoxazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-cyclohexyl)-acetic acid,   (S)-(3,5-Bis-trifluoromethyl-benzyl)-(7-methyl-1-pyridin-4-ylmethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,   (S)-(3,5-Bis-trifluoromethyl-benzyl)-(7-methyl-1-pyridin-4-ylmethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine hydrochloride,   (S)-(3,5-Bis-trifluoromethyl-benzyl)-(7-methyl-1-pyridin-3-ylmethyl-8-trifluoromethyl-2;3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,   (S)-2-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-ethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-yl}-ethanol,   (S)5-{9-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-1,3,6,7,8,9-hexahydro-2-oxa-5-aza-cyclohepta[f]inden-5-ylmethyl}-thiophene-2-carboxylic acid,   (S)-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-(5-pyridin-4-ylmethyl-3,5,6,7,8,9-hexahydro-1H-2-oxa-5-aza-cyclohepta[f]inden-9-yl)-amine,   (S)-(4-{9-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-1,3,6,7,8,9-hexahydro-2-oxa-5-aza-cyclohepta[f]inden-5-ylmethyl}-cyclohexyl)-acetic acid,   (S)-2-{9-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-1,3,6,7,8,9-hexahydro-2-oxa-5-aza-cyclohepta[f]inden-5-yl}-ethanol,   (S)-9-[[2-(2-Amino-ethyl)-2H-tetrazol-5-yl]-(3,5-bis-trifluoromethyl-benzyl)-amino]-1,3,6,7,8,9-hexahydro-2-oxa-5-aza-cyclohepta[f]indene-5-carboxylic acid tert-butyl ester,   (S)-[2-(2-Amino-ethyl)-2H-tetrazol-5-yl]-(5-benzyl-3,5,6,7,8,9-hexahydro-1H-2-oxa-5-aza-cyclohepta[f]inden-9-yl)-(3,5-bis-trifluoromethyl-benzyl)-amine,   (S)-[2-(2-Amino-ethyl)-2H-tetrazol-5-yl]-(3,5-bis-trifluoromethyl-benzyl)-[5-(3,3,3-trifluoro-propyl)-3,5,6,7,8,9-hexahydro-1H-2-oxa-5-aza-cyclohepta[f]inden-9-yl]-amine,   (S)-5-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-2,3,4,5,7,8,9,10-octahydro-naphtho[2,3-b]azepin-1-yl}-3,3-dimethyl-pentanoic acid,   (S)-(3,5-Bis-trifluoromethyl-benzyl)-(1-cyclopentylmethyl-11-methyl-2,3,4,5,7,8,9,10-octahydro-1H-naphtho[2,3-b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,   (S)-5-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-thiophene-2-carboxylic acid,   (S)-(3,5-Bis-trifluoromethyl-benzyl)-(1,7-dimethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,   (S)-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-(7-methyl-1-thiazol-2-ylmethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-amine,   (S)-(3,5-Bis-trifluoromethyl-benzyl)-[7-methyl-1-(1-methyl-1H-imidazol-2-ylmethyl)-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl]-(2-methyl-2H-tetrazol-5-amine,   (S)-5-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl},   (S)-(3,5-Bis-trifluoromethyl-benzyl)-(7-methyl-1-piperidin-4-ylmethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,   (S)-(4-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-piperidin-1-yl)-acetic acid ethyl ester,   (S)-(4-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-ylmethyl}-piperidin-1-yl)-acetic acid,   (S)-(3,5-Bis-trifluoromethyl-benzyl)-(7-methyl-1-pyrrolidin-2-ylmethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-(2-methyl-2H-tetrazol-5-yl)-amine,   (S)-[2-(2-Amino-ethyl)-2H-tetrazol-5-yl]-[1-(2-benzyloxy-ethyl)-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl]-(3,5-bis-trifluoromethyl-benzyl)-amine,   (S)-2-{5-[[2-(2-Amino-ethyl)-2H-tetrazol-5-yl]-(3,5-bis-trifluoromethyl-benzyl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-yl}-ethanol,   (S)-[2-(2-Amino-ethyl)-2H-tetrazol-5-yl]-(3,5-bis-trifluoromethyl-benzyl)-(7-methyl-1-thiazol-2-ylmethyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-amine,   (S)-(2-{5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepin-1-yl}-ethoxy)-acetic acid,   (S)-(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-[7-methyl-1-(2H-tetrazol-5-ylmethyl)-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl]-amine,   (S)-5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid 2-amino-ethyl ester,   (S)-5-[(3,5-Bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-amino]-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid 2-carboxy-2-methyl-propyl ester,   (S)-[2-(2-Amino-ethyl)-2H-tetrazol-5-yl]-(3,5-bis-trifluoromethyl-benzyl)-(1-cyclopropylmethyl-7-methyl-8-tri fluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-amine,   (S)-[2-(2-Amino-ethyl)-2H-tetrazol-5-yl]-(3,5-bis-trifluoromethyl-benzyl)-(1-cyclopropylmethyl-7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-amine hydrochloride, and pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer or mixture of diastereomers thereof.   
   
   
       8 . A method of modulating CETP activity comprising administering a therapeutically effective composition comprising a compound of Formula I, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer or mixture of diastereomers thereof to a patient in need thereof. 
   
   
       9 . The method of  claim 8  wherein modulation of CETP activity results in a decrease in LDL-cholesterol. 
   
   
       10 . A method of treating or preventing dyslipidemia comprising administering a therapeutically effective composition comprising a compound of Formula I, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate diastereomer, mixture of diastereomers thereof, to a patient in need thereof. 
   
   
       11 . A method of treating or preventing atherosclerosis comprising administering a therapeutically effective composition comprising a compound of Formula I, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer, or mixture of diastereomers thereof to a patient. 
   
   
       12 . A method of lowering plasma LDL-cholesterol in a mammal comprising administering a therapeutically effective dose of a compound of Formula I, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer, or mixture of diastereomers thereof to said mammal. 
   
   
       13 . A method of treating and/or preventing the pathological sequelae due to high levels of plasma LDL-cholesterol in a mammal comprising administering a therapeutically effective dose of a compound of Formula I, pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer, or mixture of diastereomers to said mammal. 
   
   
       14 . A pharmaceutical composition comprising a compound according to  claim 1  and at least one of: a carrier, diluent, and excipient. 
   
   
       15 . Use of a compound according to  claim 1  for the manufacture of a medicament for treating or preventing atherosclerosis in a mammal comprising administering an effective dose of a compound of Formula I, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate; diastereomer, or mixture of diastereomers thereof to said mammal.