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 having the structural Formula I′,
- or a pharmaceutically acceptable salt thereof, wherein:
- R1 is
- (1) 6-membered aryl unsubstituted or substituted by 1-3 R5, or
- (2) 5-, 6- or 9-membered heteroaryl or 9-membered bicyclic heterocycle, containing 1, 2 or 3 heteroatoms independently selected from N, O, and S, wherein the heteroaryl is unsubstituted or substituted by 1-3 R5;
- R2 is
- (1) 6-membered aryl unsubstituted or substituted by 1-3 R7,
- (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 R7,
- (3) (C1-6)alkyl,
- (4) 4- to 6-membered heterocyclyl containing 1 or 2 heteroatoms independently selected from N, O and S, or
- (5) —CH2-6-membered aryl, wherein the aryl is unsubstituted or substituted by 1-3 R7;
- R3 is
- (1) 4- to 7-membered heterocyclyl containing 1 or 2 heteroatoms independently selected from N, O and S,
- (2) 5- or 6-membered heteroaryl containing 1, 2 or 3 heteroatoms independently selected from N, O, and S,
- (3) —(C1-6)alkyl-heteroaryl, wherein the heteroaryl is a 5- or 6-membered heteroaryl containing 1, 2 or 3 heteroatoms independently selected from N, O and S,
- (4) —(C1-6)alkyl-6-membered aryl,
- (5) —(C1-6)alkyl-heterocyclyl, wherein the heterocyclyl is a 3- to 6-membered ring containing 1 or 2 heteroatoms independently selected from N, O and S,
- (6) (C1-6)alkyl,
- (7) —(C1-6)alkyl-C(O)O—(C1-4)alkyl,
- (8) —(C1-6)alkyl-S(O)2—NR9aR9b,
- (9) —(C1-6)alkyl-S(O)2—(C1-3)alkyl,
- (10) —(C1-3)alkyl-heteroaryl, wherein the heteroaryl is a 8- to 10-membered fused ring, and wherein the heteroaryl contains 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S,
- (11) —(C1-6)alkyl-S(O)2—(C3-6)cycloalkyl,
- (12) —(C1-6)alkyl-S(O)2—NR9a—(C3-6)cycloalkyl,
- (13) —(C1-6)alkyl-(C3-6)cycloalkyl,
- (14) (C3-6)cycloalkyl, or
- (15) 9- to 10-membered fused aryl,
- wherein each aryl, heteroaryl, cycloalkyl, or heterocyclyl are unsubstituted or substituted by 1-3 R6, and wherein each alkyl is unsubstituted or substituted by 1-3 R8;
- R4 is
- (1) hydrogen,
- (2) (C1-3)alkyl,
- or R3 and R4 combine along with the nitrogen atom to which they are attached to form a 4- to 7-membered mono- or 6- to 10-membered bicyclic heterocyclyl ring containing 1 or 2 heteroatoms independently selected from N, O and S, wherein the heterocyclyl ring is unsubstituted or substituted by 1-3 R6;
- R5 is
- (1) cyano,
- (2) halo,
- (3) (C1-6)alkyl,
- (4) —C(O)NH2,
- (5) —C(O)NR10aR10b,
- (6) (C3-6)cycloalkyl,
- (7) hydroxy,
- (8) hydroxy(C1-3)alkyl-,
- (9) (C1-6)alkoxy-,
- (10)-NR10aR10b
- (11) 5-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 R7;
- (12) halo(C1-6)alkyl-, or
- (13) halo(C1-6)alkoxy-;
- R6 is
- (1) (C1-3)alkyl,
- (2) halo(C1-3)alkyl-,
- (3) oxo,
- (4) (C3-6)cycloalkyl,
- (5) —C(O)O—(C1-4)alkyl,
- (6) NH2,
- (7) hydroxy,
- (8) phenyl unsubstituted or substituted by halo,
- (9) hydroxy(C1-3)alkyl-,
- (10) (C1-6)alkoxy-,
- (11) halo(C1-6)alkoxy-,
- (12) cyano, or
- (13) halo;
- R7 is
- (1) (C1-6)alkyl,
- (2) halo,
- (3) (C1-3)alkoxy-,
- (4) halo(C1-3)alkyl-,
- (5) (C3-6)cycloalkyl, or
- (6) —C(O)O—(C1-3)alkyl;
- R8 is
- (1) (C1-3)alkyl,
- (2) hydroxy(C1-3)alkyl-,
- (3) (C1-3)alkoxy-,
- (4) hydroxy,
- (5) halo(C1-3)alkyl-,
- (6) (C1-3)alkyl-S—,
- (7) —C(O)—NR9aR9b, or
- (8) phenyl;
- R9a and R9b are independently
- (1) hydrogen,
- (2) (C1-3)alkyl,
- (3) —(C1-3)alkyl-phenyl,
- (4) 5- or 6-membered heteroaryl containing 1, 2, or 3 heteroatoms independently selected from N, O, and S, or
- (5) phenyl;
- R10a and R10b are independently
- (1) hydrogen, or
- (2) (C1-3)alkyl.