INDAZOLE DERIVATIVES USEFUL AS INHIBITORS OF DIACYLGLYCERIDE O-ACYLTRANSFERASE 2

• US 20190330239A1
• Filed: 11/13/2017
• Published: 10/31/2019
• Est. Priority Date: 11/18/2016
• Status: Active Grant

• Current Assignee: Merck Sharp & Dohme LLC (Merck & Co., Inc.)
• Original Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.)
• Inventors: Shen, Dong-Ming, Graham, Thomas H., Liu, Wensheng, Tudge, Clare, Verras, Andreas, Jiang, Jinlong
• Granted Patent: US 11,104,690 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/416 condensed with carbocyclic ring systems, e.g. indazole
• CPC Class Codes: A61K 31/422 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/433 Thidiazoles
• CPC Class Codes: A61K 31/4406 only substituted in position 3, e.g. zimeldine nicotinic acid A61K31/455
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 231/56 Benzopyrazoles; Hydrogenated benzopyrazoles
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems
• CPC Class Codes: C07D 495/08 : Bridged systems
• CPC Class Codes: C07D 515/08 : Bridged systems

Abstract

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, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions.

Claims

1. A compound having structural Formula I-c′

;

2. The compound of claim 1 wherein R³ and R⁴ combine along with the nitrogen atom to which they are attached to form

3. The compound of claim 1, wherein R² is

4. The compound of claim 1, wherein R³ is

5. 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-indazole-6-carboxamide,

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

(3) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-{1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethyl}-1H-indazole-6-carboxamide,

(4) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-{1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}-1H-indazole-6-carboxamide,

(5) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-{(1S)-2-hydroxy-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-1H-indazole-6-carboxamide,

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

(7) tert-butyl 4-[1-({[3-(2-chlorophenyl)-1-(4-fluorophenyl)-1H-indazol-6-yl]carbonyl}amino)ethyl]-1H-imidazole-1-carboxylate,

(8) N-[(3R,4R)-4-amino-1,1-dioxidotetrahydrothiophen-3-yl]-3-(2-chlorophenyl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(9) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[4-hydroxy-1,1-dioxidotetrahydrothiophen-3-yl]-1H-indazole-6-carboxamide,

(10) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[6-(trifluoromethyl)pyridin-3-yl]-1H-indazole-6-carboxamide,

(11) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-{(1R)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-1H-indazole-6-carboxamide,

(12) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1S)-2-methoxy-1-methylethyl]-1H-indazole-6-carboxamide,

(13) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-{(1S)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-1H-indazole-6-carboxamide,

(14) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[1-(1H-imidazol-4-yl)ethyl]-1H-indazole-6-carboxamide,

(15) N-tert-butyl-3-(2-chlorophenyl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(16) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[1-methyl-1-(1-methyl-1H-pyrazol-4-yl)ethyl]-1H-indazole-6-carboxamide,

(17) 3-(2-chlorophenyl)-N-[1-(3,5-dimethyl-1H-pyrazol-4-yl)ethyl]-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(18) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-1H-indazole-6-carboxamide,

(19) tert-butyl N-{[3-(2-chlorophenyl)-1-(4-fluorophenyl)-1H-indazol-6-yl]carbonyl}-beta-alaninate,

(20) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(2-sulfamoylethyl)-1H-indazole-6-carboxamide,

(21) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-oxetan-3-yl-1H-indazole-6-carboxamide,

(22) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(1-methyl-5-oxopyrrolidin-3-yl)-1H-indazole-6-carboxamide,

(23) 3-(2-chlorophenyl)-6-[(3,3-dioxido-3-thia-6-azabicyclo[3.2.1]oct-6-yl)carbonyl]-1-(4-fluorophenyl)-1H-indazole,

(24) 3-(2-chlorophenyl)-N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(25) 3-(2-chlorophenyl)-N-[2-(dimethylsulfamoyl)ethyl]-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(26) 3-(2-chlorophenyl)-N-[2-(ethylsulfonyl)ethyl]-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(27) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-methyl-N-[1-(5-phenyl-1H-pyrazol-3-yl)ethyl]-1H-indazole-6-carboxamide,

(28) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-{1-methyl-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-1H-indazole-6-carboxamide,

(29) 3-(2-chlorophenyl)-N-[(1,1-dioxidotetrahydrothiophen-3-yl)methyl]-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(30) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-{(1R)-2-hydroxy-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-1H-indazole-6-carboxamide,

(31) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(pyridin-3-ylmethyl)-1H-indazole-6-carboxamide,

(32) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(pyridin-2-ylmethyl)-1H-indazole-6-carboxamide,

(33) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(pyridin-4-ylmethyl)-1H-indazole-6-carboxamide,

(34) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1S)-1-(2-methylpyrimidin-5-yl)ethyl]-1H-indazole-6-carboxamide,

(35) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(imidazo[1,2-a]pyrimidin-2-ylmethyl)-1H-indazole-6-carboxamide,

(36) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[1-(4-methyl-4H-1,2,4-triazol-3-yl)ethyl]-1H-indazole-6-carboxamide,

(37) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(isoxazol-4-ylmethyl)-1H-indazole-6-carboxamide,

(38) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(pyrimidin-5-ylmethyl)-1H-indazole-6-carboxamide,

(39) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[2-(4H-1,2,4-triazol-4-yl)ethyl]-1H-indazole-6-carboxamide,

(40) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(1,2,5-thiadiazol-3-ylmethyl)-1H-indazole-6-carboxamide,

(41) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[1-(5-methyl-1,2,4-oxadiazol-3-yl)ethyl]-1H-indazole-6-carboxamide,

(42) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(2-hydroxy-1,1-dimethylethyl)-1H-indazole-6-carboxamide,

(43) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[1-(hydroxymethyl)cyclopentyl]-1H-indazole-6-carboxamide,

(44) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1-hydroxycyclohexyl)methyl]-1H-indazole-6-carboxamide,

(45) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(2-methoxyethyl)-1H-indazole-6-carboxamide,

(46) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[2-hydroxy-1-(hydroxymethyl)-1-methylethyl]-1H-indazole-6-carboxamide,

(47) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[4-(hydroxymethyl)tetrahydro-2H-pyran-4-yl]-1H-indazole-6-carboxamide,

(48) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1R,2S)-2-hydroxy-1-(3-methyl-1,2,4-oxadiazol-5-yl)propyl]-1H-indazole-6-carboxamide,

(49) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-{[2-(trifluoromethyl)pyrimidin-5-yl]methyl}-1H-indazole-6-carboxamide,

(50) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-{(1S)-1-[2-(trifluoromethyl)pyrimidin-5-yl]ethyl}-1H-indazole-6-carboxamide,

(51) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1R)-1-methyl-2-sulfamoylethyl]-1H-indazole-6-carboxamide,

(52) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(2-oxopyrrolidin-3-yl)-1H-indazole-6-carboxamide,

(53) 3-(2-chlorophenyl)-N-[2-(cyclohexylsulfamoyl)ethyl]-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(54) N-[2-(benzylsulfamoyl)ethyl]-3-(2-chlorophenyl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(55) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[2-(pyridin-2-ylsulfamoyl)ethyl]-1H-indazole-6-carboxamide,

(56) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[2-(phenylsulfamoyl)ethyl]-1H-indazole-6-carboxamide,

(57) 3-(2-chlorophenyl)-N-(2,5-dioxopyrrolidin-3-yl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(58) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(1-oxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(59) methyl 3-({[3-(2-chlorophenyl)-1-(4-fluorophenyl)-1H-indazol-6-yl]carbonyl}) amino)tetra-hydrothiophene-3-carboxylate,

(60) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[2-(pyridin-3-ylsulfamoyl)ethyl]-1H-indazole-6-carboxamide,

(61) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[1-(hydroxymethyl)cyclopropyl]-1H-indazole-6-carboxamide,

(62) ethyl 1-({[3-(2-chlorophenyl)-1-(4-fluorophenyl)-1H-indazol-6-yl]carbonyl}amino)cyclopropanecarboxylate,

(63) methyl 1-({[3-(2-chlorophenyl)-1-(4-fluorophenyl)-1H-indazol-6-yl]carbonyl}amino)cyclopentanecarboxylate,

(64) 3-(2-chlorophenyl)-N-(3,3-difluorocyclopentyl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(65) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[1-(hydroxymethyl)propyl]-1H-indazole-6-carboxamide,

(66) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-2-hydroxycyclohexyl]-1H-indazole-6-carboxamide (cis),

(67) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-2-hydroxycyclohexyl]-1H-indazole-6-carboxamide (trans),

(68) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1S)-2-hydroxy-1-methylethyl]-1H-indazole-6-carboxamide,

(69) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1S)-1-(hydroxymethyl)-2-methylpropyl]-1H-indazole-6-carboxamide,

(70) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[4-(1-hydroxy-1-methylethyl)tetrahydro-2H-pyran-4-yl]-1H-indazole-6-carboxamide,

(71) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[3-hydroxy-3,4-dihydro-2H-chromen-4-yl]-1H-indazole-6-carboxamide,

(72) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[2-hydroxy-5-methylcyclopentyl]-1H-indazole-6-carboxamide,

(73) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[1-(2,2,2-trifluoro-1-hydroxyethyl)pentyl]-1H-indazole-6-carboxamide,

(74) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[2-hydroxy-1-(methoxymethyl)-2-phenylethyl]-1H-indazole-6-carboxamide,

(75) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[1-(hydroxymethyl)-2,3-dihydro-1H-inden-1-yl]-1H-indazole-6-carboxamide,

(76) tert-butyl 3-({[3-(2-chlorophenyl)-1-(4-fluorophenyl)-1H-indazol-6-yl]carbonyl}amino)-4-hydroxypyrrolidine-1-carboxylate,

(77) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(tetrahydrofuran-3-yl)-1H-indazole-6-carboxamide,

(78) 3-(2-chlorophenyl)-N-(1-cyclopropyl-2-hydroxyethyl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(79) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[2-hydroxy-1-methylethyl]-1H-indazole-6-carboxamide,

(80) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[2-hydroxy-1-(hydroxymethyl)-2-phenylethyl]-1H-indazole-6-carboxamide,

(81) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(3,3,3-trifluoro-2-hydroxy-1-methylpropyl)-1H-indazole-6-carboxamide,

(82) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[2-hydroxy-1-phenylethyl]-1H-indazole-6-carboxamide,

(83) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(3-hydroxycyclopentyl)-1H-indazole-6-carboxamide,

(84) 3-(2-chlorophenyl)-N-cyclopentyl-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(85) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]-1H-indazole-6-carboxamide,

(86) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(tetrahydro-2H-pyran-4-yl)-1H-indazole-6-carboxamide,

(87) 3-(2-chlorophenyl)-N-[2,3-dihydroxy-4-(hydroxymethyl)cyclopentyl]-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(88) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[1-(hydroxymethyl)cyclobutyl]-1H-indazole-6-carboxamide,

(89) methyl 3-({[3-(2-chlorophenyl)-1-(4-fluorophenyl)-1H-indazol-6-yl]carbonyl}amino)tetra-hydrothiophene-3-carboxylate 1-oxide,

(90) methyl 3-({[3-(2-chlorophenyl)-1-(4-fluorophenyl)-1H-indazol-6-yl]carbonyl}amino)tetra-hydrothiophene-3-carboxylate 1,1-dioxide,

(91) tert-butyl 6-({[3-(2-chlorophenyl)-1-(4-fluorophenyl)-1H-indazol-6-yl]carbonyl}) amino)-1,4-thiazepane-4-carboxylate 1,1-dioxide,

(92) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[3-(hydroxymethyl)-1,1-dioxidotetrahydrothiophen-3-yl]-1H-indazole-6-carboxamide,

(93) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1S)-1-(hydroxymethyl)-3-(methylsulfanyl)propyl]-1H-indazole-6-carboxamide,

(94) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[2-hydroxycyclopentyl]-1H-indazole-6-carboxamide,

(95) N-[1-carbamoyl-2-methylpropyl]-3-(2-chlorophenyl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(96) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[2-hydroxycyclopentyl]-1H-indazole-6-carboxamide,

(97) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1S,2S)-2-hydroxycyclopentyl]-1H-indazole-6-carboxamide,

(98) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[3-(hydroxymethyl)tetrahydrothiophen-3-yl]-1H-indazole-6-carboxamide,

(99) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1S)-1-(hydroxymethyl)-2,2-dimethylpropyl]-1H-indazole-6-carboxamide,

(100) tert-butyl (3 S)-3-({[3-(2-chlorophenyl)-1-(4-fluorophenyl)-1H-indazol-6-yl]carbonyl}amino)pyrrolidine-1-carboxylate,

(101) tert-butyl (3R)-3-({[3-(2-chlorophenyl)-1-(4-fluorophenyl)-1H-indazol-6-yl]carbonyl}amino)pyrrolidine-1-carboxylate,

(102) 3-(2-chlorophenyl)-N-(1,1-dioxido-1,4-thiazepan-6-yl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(103) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1S,2 S)-1-(hydroxymethyl)-2-methylbutyl]-1H-indazole-6-carboxamide,

(104) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(3-oxocyclobutyl)-1H-indazole-6-carboxamide,

(105) 3-(2-chlorophenyl)-N-(1-cyanocyclopropyl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(106) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1R,2S)-2-hydroxy-1-methyl-2-phenylethyl]-1H-indazole-6-carboxamide,

(107) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1R,2R)-2-hydroxy-1-methyl-2-phenylethyl]-1H-indazole-6-carboxamide,

(108) N-[1-(4-bromophenyl)-3-hydroxycyclobutyl]-3-(2-chlorophenyl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(109) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(3-morpholin-4-yl-1-phenylpropyl)-1H-indazole-6-carboxamide,

(110) N-[(1S)-1-benzyl-2-hydroxyethyl]-3-(2-chlorophenyl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(111) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-((2S,3 S,4S,6S)-3-hydroxy-6-methoxy-2-methyltetrahydro-2H-pyran-4-yl)-1H-indazole-6-carboxamide,

(112) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(1-methyl-2-pyridin-2-ylethyl)-1H-indazole-6-carboxamide,

(113) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-(3-hydroxy-1,1-dimethylbutyl)-1H-indazole-6-carboxamide,

(114) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1-hydroxycyclopropyl)methyl]-1H-indazole-6-carboxamide,

(115) 3-(2-chlorophenyl)-1-(4-fluorophenyl)-N-[(1R,2S)-2-hydroxycyclopentyl]-1H-indazole-6-carboxamide,

(167) 1-Benzyl-3-(2-chlorophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(168) 1-(4-chlorobenzyl)-3-(2-chlorophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(169) 3-(2-chlorophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(1-methylethyl)-1H-indazole-6-carboxamide,

(170) 3-(2-chlorophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorobenzyl)-1H-indazole-6-carboxamide,

(171) 3-(2-chlorophenyl)-1-(5-chloropyridin-2-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(172) 3-(2-chlorophenyl)-1-(5-fluoropyridin-2-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(173) 3-(2-chlorophenyl)-1-(5-chloropyridin-2-yl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(174) 3-(2-chlorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-pyridin-2-yl-1H-indazole-6-carboxamide,

(175) 3-(2-chlorophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-pyridin-2-yl-1H-indazole-6-carboxamide,

(176) 3-(2-chlorophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(5-fluoropyridin-2-yl)-1H-indazole-6-carboxamide,

(179) 3-(2-Chlorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-(thiazol-4-yl)-1H-indazole-6-carboxamide,

(180) methyl 3-{3-(2-chlorophenyl)-6-[(3-methyl-1,1-dioxidotetrahydrodioxidotetrahydrodioxidotetrahydrodioxidotetrahydro-thiophen-3-yl)carbamoyl]-1H-indazol-1-yl}benzoate,

(181) 3-(2-chlorophenyl)-1-(5-fluoropyrimidin-2-yl)-N-(3-methyl-1,1-dioxidotetradioxidotetradioxidotetradioxidotetra-hydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(182) 3-(2-chlorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]-1H-indazole-6-carboxamide,

(183) 1-(5-tert-butyl-1,3,4-thiadiazol-2-yl)-3-(2-chlorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(184) 3-(2-chlorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-(1-methyl-1H-pyrazol-3-yl)-1H-indazole-6-carboxamide,

(185) 3-(2-chlorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-(5-methylpyridin-2-yl)-1H-indazole-6-carboxamide,

(186) 3-(2-chlorophenyl)-1-(6-methoxypyridin-2-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(187) methyl 4-{3-(2-chlorophenyl)-6-[(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)carbamoyl]-1H-indazol-1-yl}benzoate,

(188) ethyl 2-{3-(2-chlorophenyl)-6-[(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)carbamoyl]-1H-indazol-1-yl}-1,3-oxazole-4-carboxylate,

(189) 3-(2-chlorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-pyridin-3-yl-1H-indazole-6-carboxamide,

(190) 3-(2-chlorophenyl)-1-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide, and

(191) 3-(2-Chlorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-6-carboxamide,

or a pharmaceutically acceptable salt thereof.

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

(116) 3-(3-cyanophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(117) 3-(3-cyanophenyl)-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(118) 3-(2-chloro-5-cyanophenyl)-1-(4-fluorophenyl)-N-[1-(hydroxymethyl)cyclobutyl]-1H-indazole-6-carboxamide,

(119) 3-(2-chloro-5-cyanophenyl)-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(120) 3-(2-chloro-5-cyanophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(121) 3-(5-carbamoyl-2-chlorophenyl)-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(122) 3-(5-carbamoyl-2-chlorophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(123) 3-(2-chloro-5-cyanophenyl)-1-(4-fluorophenyl)-N-[(1S)-1-(hydroxymethyl)-2-methylpropyl]-1H-indazole-6-carboxamide,

(124) 3-(3-cyclopropylphenyl)-1-(5-fluoropyridin-2-yl)-N-[(1S)-1-(hydroxymethyl)-2-methylpropyl]-1H-indazole-6-carboxamide,

(125) 3-(3-cyclopropylphenyl)-1-(5-fluoropyridin-2-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(126) 3-(3-cyclopropylphenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(5-fluoropyridin-2-yl)-1H-indazole-6-carboxamide,

(127) 3-(2-chloro-5-cyanophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(5-fluoropyridin-2-yl)-1H-indazole-6-carboxamide,

(128) 3-[3-(difluoromethoxy)phenyl]-1-(5-fluoropyridin-2-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(129) 3-(3-Cyanophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(130) 3-(2,3-dichlorophenyl)-N-(1,1-dioxidotetrahydro-thiophen-3-yl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(131) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-3-(3-methoxyphenyl)-1H-indazole-6-carboxamide,

(132) 3-(2,6-difluorophenyl)-N-(1,1-dioxidotetrahydro-thiophen-3-yl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

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

(134) N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-3-pyridin-3-yl-1H-indazole-6-carboxamide,

(135) 3-(2-chloropyridin-3-yl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(136) 3-[3-(difluoromethoxy)phenyl]-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(137) 3-(5-chloro-2-methoxypyridin-4-yl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(138) 3-(5-chloro-2-methoxypyridin-3-yl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(4-fluorophenyl)-1H-indazole-6-carboxamide,

(139) 3-(1,3-benzodioxol-5-yl)-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(140) 1-(4-fluorophenyl)-3-(2-methoxypyridin-4-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(141) 3-(5-chloro-2-methoxypyridin-4-yl)-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(142) 3-(5-chloro-2-methoxypyridin-3-yl)-1H-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(143) 3-[3-(difluoromethoxy)phenyl]-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(144) 1-(4-fluorophenyl)-3-(3-methoxyphenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(145) 3-(3-cyclopropylphenyl)-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(146) 3-(5-cyanopyridin-3-yl)-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(147) 1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-[3-(2,2,2-trifluoroethoxy)phenyl]-1H-indazole-6-carboxamide,

(148) 3-[3-(dimethylcarbamoyl)phenyl]-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(149) 3-(3-carbamoylphenyl)-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(150) 1-(4-fluorophenyl)-3-[3-(1-hydroxy-1-methylethyl)phenyl]-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(151) 3-(5-cyano-2-fluorophenyl)-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(152) 3-(6-chloro-2-fluoropyridin-3-yl)-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(153) 1-(4-fluorophenyl)-3-(5-fluoropyridin-3-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(154) 1-(4-fluorophenyl)-3-(2-fluoropyridin-3-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(155) 1-(4-fluorophenyl)-3-(6-methoxypyridin-3-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(156) 1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-(3-methylphenyl)-1H-indazole-6-carboxamide,

(157) 3-(3,5-dichlorophenyl)-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(158) 3-(3-chlorophenyl)-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(159) 1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-[2-(trifluoromethyl)pyridin-4-yl]-1H-indazole-6-carboxamide,

(160) 3-[2-chloro-5-(trifluoromethyl)phenyl]-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(161) 3-(5-cyano-2-fluoro-3-methoxyphenyl)-1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(162) 1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-phenyl-1H-indazole-6-carboxamide,

(163) 1-(4-fluorophenyl)-3-(1-methyl-1H-benzotriazol-6-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

(164) 1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-[3-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]-1H-indazole-6-carboxamide,

(165) 1-(4-fluorophenyl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-3-[3-(1H-pyrazol-1-yl)phenyl]-1H-indazole-6-carboxamide,

(166) 3-(6-((1,1-dioxidotetrahydrothiophen-3-yl)carbamoyl)-1-(4-fluorophenyl)-1H-indazol-3-yl)pyridine 1-oxide,

(177) 3-(3-cyanophenyl)-N-(1,1-dioxidotetrahydrothiophen-3-yl)-1-(5-fluoropyridin-2-yl)-1H-indazole-6-carboxamide, and

(178) -(3-cyanophenyl)-1-(5-fluoropyridin-2-yl)-N-(3-methyl-1,1-dioxidotetrahydrothiophen-3-yl)-1H-indazole-6-carboxamide,

or a pharmaceutically acceptable salt thereof.

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

8. (canceled)

9. (canceled)

10. (canceled)

11. (canceled)

12. 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′

,

14. The method according to claim 12 for treating non-alcoholic steatohepatitis.

13. (canceled)