Indole derivatives useful as inhibitors of diacylglyceride O-acyltransferase 2

1. A compound having structural Formula I:

or a pharmaceutically acceptable salt thereof wherein:

R 1 is

(1) aryl unsubstituted or substituted by 1-3 R 5 , or

(2) 5- or 6-membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from N, O, and S, wherein the heteroaryl is unsubstituted or substituted by 1-3 R 5 , or

(3) 8- to 10-membered fused heteroaryl containing 1, 2, or 3 heteroatoms independently selected from N, O, and S, wherein the heteroaryl is unsubstituted or substituted by 1-3 R 5 ;

R 2 is

R 3 is

(1) —(C 1-6 )alkyl-O—(C 1-3 )alkyl,

(2) 4- to 7-membered monocyclic or 6- to 10-membered bicyclic heterocyclyl containing 1 or 2 heteroatoms independently selected from N, O, and S, wherein the heterocyclyl is unsubstituted or substituted by 1-3 R 7 ,

(3) —(C 1-6 )alkyl-heterocyclyl containing 1 or 2 heteroatoms independently selected from N, O, and S, and wherein the heterocyclyl is a 5- to 7-membered ring, or

(4) —(C 1-6 )alkyl-pyridinyl, wherein the pyridinyl is unsubstituted or substituted with (C 1-3 )alkyl or halo(C 1-3 )alkyl, and wherein the alkyl is unsubstituted or substituted with a hydroxy;

R 4 is

(1) hydrogen,

(2) (C 1-3 )alkyl, or

(3) CN;

each R 5 is

(1) halo,

(2) (C 1-3 )alkyl,

(3) halo(C 1-3 )alkyl,

(4) (C 3-6 )cycloalkyl,

(5) —C(O)NH 2 ,

(6) —C(O)O(C 1-3 )alkyl,

(7) (C 1-3 )alkoxy,

(8) halo(C 1-3 )alkoxy,

(9) hydroxy,

(10) phenyl,

(11) —NHC(O)CH 3 ,

(12) 5- or 6-membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from N, O, and S, wherein the heteroaryl is unsubstituted or substituted by 1-2 (C 1-3 )alkyl, or hydroxy,

(13) CN,

(14) hydroxy(C 1-3 )alkyl, or

(15) (C 1-3 )alkyl-heterocyclyl, wherein the heterocyclyl contains 1 or 2 heteroatoms independently selected from N, O, or S, and wherein the heterocyclyl is a 5- to 7-membered ring;

each R 6 is

(1) hydrogen, or

(2) halo;

each R 7 is

(1) oxo, or

(2) (C 1-3 )alkyl;

X is CH or N;

Y is CH or N;

n is 1 or 2.

2. The compound of claim 1 , wherein R 3 is —(C 1-6 )alkyl-O—(C 1-3 )alkyl; a 5- to 7-membered heterocyclyl containing 1 or 2 heteroatoms independently selected from N, O, and S, wherein the heterocyclyl is unsubstituted or substituted by 1-3 R 7 ; or —(C 1-6 )alkyl-heterocyclyl containing 1 or 2 heteroatoms independently selected from N, O, and S, and wherein the heterocyclyl is a 5- to 7-membered ring, or a pharmaceutically acceptable salt thereof.

3. The compound of claim 2 , wherein R 2 is

or a pharmaceutically acceptable salt thereof.

4. The compound of claim 2 , wherein R 3 is

or a pharmaceutically acceptable salt thereof.

5. The compound of claim 4 , wherein R 2 is

or a pharmaceutically acceptable salt thereof.

6. The compound of claim 4 , wherein R 3 is

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 6 , wherein R 2 is

or a pharmaceutically acceptable salt thereof.

8. The compound claim 1 , wherein R 2 is

or a pharmaceutically acceptable salt thereof.

9. A compound of claim 1 , selected from the group consisting of

(1) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indole-6-carboxamide,

(2) 3-(2-Chlorophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(3) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(1-methoxypropan-2-yl)-1H-indole-6-carboxamide,

(4) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(2-methyl-1-morpholinopropan-2-yl)-1H-indole-6-carboxamide,

(5) (S)-3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(2-hydroxy-1-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-1H-indole-6-carboxamide,

(6) (S)-3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(1-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-1H-indole-6-carboxamide

(7) (R)-3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(1-(6-(trifluoromethyl)pyridin-3-yl)ethyl)-1H-indole-6-carboxamide,

(8) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-2-methyl-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indole-6-carboxamide,

(9) 3-(2-chlorophenyl)-2-cyano-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indole-6-carboxamide,

(10) 3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyridin-2-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indole-6-carboxamide,

(11) 3-(3-cyclopropylphenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(5-fluoropyridin-2-yl)-1H-indole-6-carboxamide,

(12) 3-(3-cyclopropylphenyl)-1-(5-fluoropyridin-2-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indole-6-carboxamide,

(13) 3-(3-(difluoromethoxy)phenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(5-fluoropyridin-2-yl)-1H-indole-6-carboxamide,

(14) 3-(2-chlorophenyl)-1-(5-fluoropyridin-2-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indole-6-carboxamide,

(15) 3-(2-chlorophenyl)-1-(5-fluoropyrimidin-2-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indole-6-carboxamide,

(16) 3-(3-cyclopropylphenyl)-1-(5-fluoropyrimidin-2-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indole-6-carboxamide,

(17) 3-(3-cyclopropylphenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(5-fluoropyrimidin-2-yl)-1H-indole-6-carboxamide,

(18) 3-(3-(difluoromethoxy)phenyl)-1-(5-fluoropyrimidin-2-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indole-6-carboxamide,

(19) 3-(3-(difluoromethoxy)phenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(5-fluoropyrimidin-2-yl)-1H-indole-6-carboxamide,

(20) 3-(4,6-dimethylpyridin-2-yl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(21) 3-(4-chloropyridin-2-yl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(22) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-3-(pyridin-2-yl)-1H-indole-6-carboxamide,

(23) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-3-(4-methylpyridin-2-yl)-1H-indole-6-carboxamide,

(24) 1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-(4-methylpyridin-2-yl)-1H-indole-6-carboxamide,

(25) 3-(5-(difluoromethoxy)pyridin-3-yl)-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indole-6-carboxamide,

(26) 3-(3-Cyclopropylphenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(27) 3-(3-(difluoromethoxy)phenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(28) 3-(3-(difluoromethoxy)phenyl)-1-(4-fluorophenyl)-2-methyl-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indole-6-carboxamide,

(29) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-3-(2-methoxyphenyl)-1H-indole-6-carboxamide,

(30) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-3-[3-(trifluoromethyl)phenyl]-1H-indole-6-carboxamide,

(31) 3-(3-chlorophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(32) methyl 3-{6-[(1,1-dioxidotetrahydrothiophen-3-yl)carbamoyl]-1-(4-fluorophenyl)-1H-indol-3-yl}benzoate,

(33) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-3-(3-methoxyphenyl)-1H-indole-6-carboxamide,

(34) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-3-(3-methylphenyl)-1H-indole-6-carboxamide,

(35) N-(1,1-dioxidotetrahydrothiophen-3-yl)-3-(3-fluorophenyl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(36) 3-biphenyl-3-yl-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(37) 3-[3-(acetylamino)phenyl]-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(38) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-3-[3-(1H-pyrazol-1-yl)phenyl]-1H-indole-6-carboxamide,

(39) 3-[3-(difluoromethoxy)phenyl]-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(40) N-(1,1-dioxidotetrahydrothiophen-3-yl)-3-(2-fluorophenyl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(41) 3-(3,5-dichlorophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(42) 3-[2-(difluoromethoxy)phenyl]-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(43) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-3-phenyl-1H-indole-6-carboxamide,

(44) 3-(2,3-dichlorophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(45) 3-(3-cyanophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(46) 3-(3-cyclopropylphenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(47) 3-(2,6-dichlorophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(48) 3-(2,6-difluorophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(49) 3-(2-chloro-6-fluorophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(50) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-3-pyrimidin-5-yl-1H-indole-6-carboxamide,

(51) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1′-methyl-1H,1′H-3,5′-biindole-6-carboxamide,

(52) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-3-pyridin-3-yl-1H-indole-6-carboxamide,

(53) 3-(3,5-dimethylisoxazol-4-yl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(54) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-indole-6-carboxamide,

(55) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-3-(4-methylphenyl)-1H-indole-6-carboxamide,

(56) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-3-[4-(1H-pyrazol-1-yl)phenyl]-1H-indole-6-carboxamide,

(57) 3-[4-(difluoromethoxy)phenyl]-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide,

(58) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-3-[3-(trifluoromethoxy)phenyl]-1H-indole-6-carboxamide,

(59) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-3-(3-hydroxyphenyl)-1H-indole-6-carboxamide,

(60) methyl 4-{6-[(1,1-dioxidotetrahydrothiophen-3-yl)carbamoyl]-1-(4-fluorophenyl)-1H-indol-3-yl}thiophene-2-carboxylate, and

(61) 3-[3-(3,5-dimethyl-1H-pyrazol-1-yl)phenyl]-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indole-6-carboxamide;

or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising of the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

11. A method of treating atherosclerosis, hepatic steatosis, atherosclerosis, type-2 diabetes mellitus, obesity, hyperlipidemia, non-alcoholic steatohepatitis 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 .

12. The method according to claim 11 for treating atherosclerosis.

13. The method according to claim 11 for treating non-alcoholic steatohepatitis.