Tetrahydroisoquinoline derivatives useful as inhibitors of diacylglyceride O-acyltransferase 2
View Patent ↗The present invention relates to a compound represented by formula I: and pharmaceutically acceptable salts thereof. The compounds of formula I are inhibitors of diacylglyceride O-acyltransferase 2 (“DGAT2”) and may be useful in the treatment, prevention and suppression of diseases mediated by DGAT2. The compounds of the present invention may be useful in the treatment of hepatic steatosis, diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cardio renal diseases such as chronic kidney diseases and heart failure and related diseases and conditions.
1. A compound having structural Formula I:
or a pharmaceutically acceptable salt thereof wherein:
L is
(1) —CH 2 —, or
(2) —C(O)—;
M is
(1) —N(R 4 )—,
(2) *—N(R 4 )—(C 1-3 )alkylene wherein the alkylene is unsubstituted or substituted by (C 1-3 )alkyl, hydroxy(C 1-3 )alkyl, or morpholinyl,
(3) *—N(R 4 )—C(O)—,
(4) *—N(R 4 )—C(O)-heterocyclyl-, wherein the heterocyclyl is a 4- to 6-membered monocyclic ring containing 1-2 heteroatoms selected from the group consisting of N, O, and S,
(5) *—N(R 4 )—(C 3-6 )cycloalkyl-,
(6) *—N(R 4 )—(C 1-2 )alkyl-(C 3-6 )cycloalkyl-, or
(7)
wherein * indicates the point of attachment to group L;
X is
(1) —O—, or
(2) —NH—;
R 1 is
(1) (C 1-6 )alkyl,
(2) halo(C 1-8 )alkyl, or
(3) (C 3-6 )cycloalkyl-;
ring A is
(1) 4- to 6-membered heterocyclyl containing 1-2 heteroatoms selected from the group consisting of N, O, and S,
(2) aryl,
(3) fused phenyl,
(4) 5- or 6-membered heteroaryl containing 1-4 heteroatoms selected from the group consisting of N, O, and S, or
(5) fused 8- to 10-membered heteroaryl containing 1-4 heteroatoms selected from the group consisting of N, O, and S;
R 2 is
(1) (C 1-6 )alkyl,
(2) halo(C 1-6 )alkyl,
(3) (C 1-6 )alkoxy,
(4) halo(C 1-6 )alkoxy,
(5) cyano,
(6) aryl,
(7) 5- or 6-membered heteroaryl containing 1-4 heteroatoms selected from the group consisting of N, O, or S,
(8) fused 8- to 10-membered heteroaryl containing 1-4 heteroatoms selected from the group consisting of N, O, and S,
(9) oxo,
(10) (C 3-6 )cycloalkyl, or
(11) halo;
R 3 is
(1) (C 1-6 )alkyl,
(2) halo(C 1-6 )alkyl,
(3) (C 1-6 )alkoxy,
(4) halo(C 1-6 )alkoxy,
(5) —CO 2 (C 1-6 )alkyl,
(6) halo, or
(7) hydroxy;
R 4 is
(1) hydrogen, or
(2) (C 1-3 )alkyl;
m is 0, 1, 2, or 3; and
n is 0, 1 or 2.
2. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein L is —CH 2 —.
3. The compound of claim 2 or a pharmaceutically acceptable salt thereof wherein M is *—N(R 4 )—C(O)—, or *—N(R 4 )—C(O)-heterocyclyl-, wherein the heterocyclyl is a 5- to 6-membered monocyclic ring containing 1-2 heteroatoms selected from the group consisting of N, O, and S; wherein * indicates the point of attachment to group L.
4. The compound of claim 3 or a pharmaceutically acceptable salt thereof wherein X is —NH—.
5. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein L is —C(O)—.
6. The compound of claim 5 or a pharmaceutically acceptable salt thereof wherein M is —N(R 4 )—; *—N(R 4 )—(C 1-3 )alkylene wherein the alkylene is unsubstituted or substituted by (C 1-3 )alkyl, hydroxy(C 1-3 )alkyl or morpholinyl; *—N(R 4 )—(C 3-6 )cycloalkyl-; *—N(R 4 )—(C 1-2 )alkyl-(C 3-6 )cycloalkyl- or
wherein * indicates the point of attachment to group L.
7. The compound of claim 6 or a pharmaceutically acceptable salt thereof wherein X is —NH—.
8. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein ring A is ring A is 5- or 6-membered heteroaryl containing 1-4 heteroatoms selected from the group consisting of N, O, and S or fused 8- to 10-membered heteroaryl containing 1-4 heteroatoms selected from the group consisting of N, O, and S.
9. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein ring A is pyrazolyl, isoquinolinyl, quinolinyl, imidazolyl, 1H-benzo[d]imidazolyl, imidazo[1,2-a]pyrimidinyl, imidazo[1,2-a]pyridinyl, benzo[c][1,2,5]oxadiazolyl, imidazo[2,1-b]thiazolyl, pyridinyl, 1,7-naphthyridinyl, imidazo[2,1-b][1,3,4]thiadiazolyl, isoxazolyl, 1,2,4-oxadiazolyl, isothiazolyl, pyrazolo[1,5-a]pyridinyl, 6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazolyl, 1H-benzo[d][1,2,3]triazolyl, 1,4,5,6-tetrahydrocyclopenta[c]pyrazolyl, 1H-1,2,3-triazolyl, pyrimidinyl, 1H-1,2,4-triazolyl, oxazolyl, or 1,2,5-oxadiazolyl.
10. The compound of claim 1 or a pharmaceutically acceptable salt thereof wherein ring A is aryl or fused phenyl.
11. The compound of claim 1 , which is
1
methyl 3-(2-(tert-butylcarbamoyl)-8-((1-(4-(trifluoromethyl)phenyl)piperidine-4-
carboxamido)methyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)benzoate;
2
N-(tert-butyl)-5-(3-(trifluoromethoxy)phenyl)-8-((3-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)methyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide;
3
methyl 3-(8-((3-(tert-butyl)-1-methyl-1H-pyrazole-5-carboxamido)methyl)-2-(tert-
butylcarbamoyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)benzoate;
4
N-(tert-butyl)-5-(3-methoxyphenyl)-8-((3-(trifluoromethyl)-1H-pyrazole-5-
carboxamido)methyl)-3,4-dihydroisoquinoline-2(1H)-carboxamide;
5
N-((2-(tert-butylcarbamoyl)-5-(3-methoxyphenyl)-1,2,3,4-tetrahydroisoquinolin-8-
yl)methyl)isoquinoline-1-carboxamide;
6
N 2 -(tert-butyl)-N 8 -(2-(5-chloro-1H-benzo[d]imidazol-2-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
7
N 2 -(tert-butyl)-N 8 -(2-(5,6-dichloro-1H-benzo[d]imidazol-2-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
8
N 2 -(tert-butyl)-N 8 -(2-(5-fluoro-1H-benzo[d]imidazol-2-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
9
N 8 -(2-(1H-benzo[d]imidazol-2-yl)ethyl)-N 2 -(tert-butyl)-5-(3-(trifluoromethyl)phenyl)-
3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
10
N 2 -(tert-butyl)-N 8 -(isoquinolin-4-ylmethyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
11
N 2 -(tert-butyl)-N 8 -(quinolin-8-ylmethyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
12
N 2 -(tert-butyl)-N 8 -(isoquinolin-5-ylmethyl)-5-(3-(trifluoromethy)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
13
N 2 -(tert-butyl)-N 8 -(2-(6-methoxy-1H-benzo[d]imidazol-2-yl)ethyl)-5-(3-
(trifluoromethoxy)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
14
N 2 -(tert-butyl)-N 8 -(2-(5-methyl-1H-benzo[d]imidazol-2-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
15
N 2 -(tert-butyl)-N 8 -((2-methylimidazo[1,2-a]pyridin-3-yl)methyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
16
N2-(tert-butyl)-N 8 -(quinolin-5-ylmethyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
17
N 8 -(benzo[c][l,2,5]oxadiazol-5-ylmethyl)-N 2 -(tert-butyl)-5-(3-(trifluoromethyl)phenyl)-
3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
18
N 2 -(tert-butyl)-N 8 -(2-(imidazo[2,l-b]thiazol-6-yl)ethyl)-5-(3-(trifluoromethyl)phenyl)-
3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
19
N 2 -(tert-butyl)-N 8 -(isoquinolin-1-ylmethyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
20
N 2 -(tert-butyl)-N 8 -(2-(1-methyl-1H-benzo[d]imidazol-2-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
21
R)-N 2 -(tert-butyl)-N 8 -(2-hydroxy-1-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
22
N 2 -(tert-butyl)-N 8 -(isoquinolin-1-ylmethyl)-5-(3-(trifluoromethoxy)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
23
N 2 -(tert-butyl)-N 8 -(2-(imidazo[1,2-a]pyridin-2-yl)ethyl)-5-(3-(trifluoromethyl)phenyl)-
3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
24
N 8 -((1,7-naphthyridin-8-yl)methyl)-N 2 -(tert-butyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
25
N 2 -(tert-butyl)-N 8 -(2-(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
26
N 2 -(tert-butyl)-N 8 -(quinolin-4-ylmethyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
27
N 2 -(tert-butyl)-N 8 -((3-cyanoisoxazol-4-yl)methyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
28
N 2 -(tert-butyl)-N 8 -((5-phenyl-1,2,4-oxadiazol-3-yl)methyl)-5-)3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
29
N 2 -(tert-butyl)-N 8 -(2-(thiazol-4-yl)ethyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide:
30
N 2 -(tert-butyl)-N 8 -(pyrazolo[1,5-a]pyridin-3-ylmethyl)-5-(3-(trifluoromethyl)phenyl)-
3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
31
N 2 -(tert-butyl)-N 8 -(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
32
N 2 -(tert-butyl)-N 8 -((5-methyl-2-phenylthiazol-4-yl)methyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
33
N 2 -(tert-butyl)-N 8 -((3-(pyridin-2-yl)-1,2,4-oxadiazol-5-yl)methyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
34
N 8 -(2-(1H-benzo[d][1,2,3]triazol-1-yl)ethyl)-N 2 -(tert-butyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
35
N 2 -(tert-butyl)-N 8 -((1,4,5,6-tetrahydrocyclopenta[c]pyrazol-3-yl)methyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
36
N 2 -(tert-butyl)-N 8 -(2-morpholino-2-(pyridin-2-yl)ethyl)-5-(3-(trifluoromethyl)phenyl)-
3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
37
N 2 -(tert-butyl)-N 8 -(2-(5-phenyl-1H-1,2,3-triazol-1-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
38
N 2 -(tert-butyl)-N 8 -(2-(4-methyl-6-(trifluoromethyl)pyrimidin-2-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
39
N 2 -(tert-butyl)-N 8 -((4-phenylthiazol-5-yl)methyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
40
N 2 -(tert-butyl)-N 8 -(2-(trifluoromethyl)phenethyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
41
N 2 -(tert-butyl)-N 8 -((2,4-dimethylthiazol-5-yl)methyl)-5-(3-(trifluoromethyl)phenyl)-
3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
42
N 8 -(2-(1H-1,2,4-triazol-5-yl)ethyl)-N 2 -(tert-butyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
43
N 2 -(tert-butyl)-N 8 -(2-(3,4-dihydroquinolin-1(2H)-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
44
N 8 -(2-(1H-pyrazol-1-yl)propyl)-N 2 -(tert-butyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
45
N 2 -(tert-butyl)-N 8 -(2-(oxazol-2-yl)propyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
46
N 2 -(tert-butyl)-N 8 -(2-(isoxazol-5-yl)propyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
47
N 2 -(tert-butyl)-N 8 -(2-(5-methyl-4H-1,2,4-triazol-3-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
48
N 8 -(2-(1H-1,2,4-triazol-1-yl)ethyl)-N 2 -(tert-butyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
49
N 2 -(tert-butyl)-N 8 -(2-(imidazo[1,2-a]pyrimidin-2-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
50
N 2 -(tert-butyl)-N 8 -(2-(3,5-dimethylisoxazol-4-yl)ethyl)-5-(3-(trifluoromethyl)phenyl)-
3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
51
N 2 -(tert-butyl)-N 8 -((6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl)methyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
52
N 2 -(tert-butyl)-N 8 -(4-(trifluoromethyl)phenethyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
53
N 8 -(4-(1H-benzo[d]imidazol-2-yl)-1,2,5-oxadiazol-3-yl)-N 2 -(tert-butyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
54
N 2 -(tert-butyl)-N 8 -(2-(imidazo[1,2-a]pyridin-3-yl)ethyl)-5-(3-(trifluoromethyl)phenyl)-
3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
55
N 2 -(tert-butyl)-N 8 -(imidazo[1,2-a]pyrimidin-2-ylmethyl)-5-(3-
(trifluoromethoxy)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
56
N 2 -(tert-butyl)-N 8 -(2-(2-methyl-1H-imidazol-1-yl)ethyl)-5-(3-(trifluoromethyl)phenyl)-
3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
57
N-(tert-butyl)-8-(2-phenylpiperidine-1-carbonyl)-5-(3-(trifluoromethoxy)phenyl)-3,4-
dihydroisoquinoline-2(1H)-carboxamide;
58
N 2 -(tert-butyl)-N 8 -(2-(6-chloro-1H-benzo[d]imidazol-2-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
59
N 8 -(2-(6-methoxy-1H-benzo[d]imidazol-2-yl)ethyl)-N 2 -(2,2,2-trifluoroethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
60
N 2 -(tert-butyl)-N 8 -(2-(5-methyl-4H-1,2,4-triazol-3-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
61
N 8 -(2-(1H-1,2,4-triazol-1-yl)ethyl)-N 2 -(tert-butyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
62
N 8 -(1-(4H-1,2,4-triazol-3-yl)ethyl)-N 2 -(tert-butyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
63
N 2 -(tert-butyl)-N 8 -(1-(pyridin-2-yl)cyclopropyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
64
N 2 -(tert-butyl)-N 8 -(1-(imidazo[2,1-b][1,3,4]thiadiazol-6-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
65
N 2 -(tert-butyl)-N 8 -((1R)-2-phenylcyclopropyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
67
N 2 -(tert-butyl)-N 8 -((4-methyl-1,2,5-oxadiazol-3-yl)methyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
68
N 2 -(tert-butyl)-N 8 -((1-methyl-1H-imidazol-2-yl)methyl)-5-(3-(trifluoromethyl)phenyl)-
3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
69
N 2 -(tert-butyl)-N 8 -(((1R,2R)-2-phenylcyclopropyl)methyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
70
N 8 -(2-(1H-1,2,4-triazol-5-yl)ethyl)-N 2 -(tert-butyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
71
N 8 -(2-(4H-1,2,4-triazol-4-yl)ethyl)-N 2 -(tert-butyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
72
N 8 -(1-(1,3,4-thiadiazol-2-yl)ethyl)-N 2 -(tert-butyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
73
N 2 -(tert-butyl)-N 8 -(1-(3-(pyridin-2-yl)-1,2,4-oxadiazol-5-yl)ethyl)-5-(3-
(trifluoromethoxy)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
74
N 2 -(tert-butyl)-N 8 -(imidazo[2,1-b]thiazol-6-ylmethyl)-5-(3-(trifluoromethoxy)phenyl)-
3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
75
N 2 -(tert-butyl)-N 8 -((6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazol-3-yl)methyl)-5-(3-
(trifluoromethoxy)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
76
N 8 -(2-(1H-1,2,3-triazol-1-yl)ethyl)-N 2 -(tert-butyl)-5-(3-(trifluoromethoxy)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
77
N 2 -(tert-butyl)-N 8 -(2-(oxazol-5-yl)propyl)-5-(3-(trifluoromethoxy)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
78
N 2 -(tert-butyl)-N 8 -(2-(pyridin-3-yl)propyl)-5-(3-(trifluoromethoxy)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide;
79
N 2 -(tert-butyl)-N 8 -(pyrazolo[1,5-a]pyridin-7-ylmethyl)-5-(3-(trifluoromethoxy)phenyl)-
3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
80
N 2 -(tert-butyl)-N 8 -((3-(pyridin-2-yl)isoxazol-5-yl)methyl)-5-(3-
(trifluoromethoxy)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide; or
81
N 2 -(tert-butyl)-N 8 -(pyrazolo[1,5-a]pyridin-3-ylmethyl)-5-(3-(trifluoromethoxy)phenyl)-
3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
or a pharmaceutically acceptable salt thereof.
12. The compound of claim 1 , which is
1
(R)-N 2 -(tert-butyl)-N 8 -(2-hydroxy-1-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide;
2
(S)-N 2 -(tert-butyl)-N 8 -(2-hydroxy-1-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide,
3
N 2 -(tert-butyl)-N 8 -((1R)-2-phenylcyclopropyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide,
4
N 2 -(tert-butyl)-N 8 -((1S,2R)-2-phenylcyclopropyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide,
5
N 2 -(tert-butyl)-N 8 -((1R,2S)-2-phenylcyclopropyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide,
6
N 2 -(tert-butyl)-N 8 -(((1R,2R)-2-phenylcyclopropyl)methyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide,
7
N 2 -(tert-butyl)-N 8 -(((1S,2S)-2-phenylcyclopropyl)methyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide,
8
N 2 -(tert-butyl)-N 8 -(imidazo[1,2-a]pyridin-3-ylmethyl)-5-(3-(trifluoromethyl)phenyl)-
3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide,
or a pharmaceutically acceptable salt thereof.
13. The compound of claim 1 , which is
1
(R/S)-N 2 -(tert-butyl)-N 8 -(2-hydroxy-1-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide,
2
N 2 -(tert-butyl)-N 8 -((trans)-2-phenylcyclopropyl)-5-(3-(trifluoromethyl)phenyl)-3,4-
dihydroisoquinoline-2,8(1H)-dicarboxamide,
3
N 2 -(tert-butyl)-N 8 -(((trans)-2-phenylcyclopropyl)methyl)-5-(3-
(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline-2,8(1H)-dicarboxamide,
or a pharmaceutically acceptable salt thereof.
14. A pharmaceutical composition comprising of the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
15. A method of treating atherosclerosis, hepatic steatosis, atherosclerosis, type-2 diabetes mellitus, obesity, hyperlipidemia, or hypercholesterolemia in a patient in need of treatment comprising the administration to the patient of a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.
16. The method according to claim 15 for treating atherosclerosis.