US 10,294,207 B2 · Pyrazole derivatives as TNIK, IKKϵ and TBK1 inhibitor and pharmaceutical composition comprising same

Abstract

Provided is pyrazole derivatives as a TNIK (Traf2- and NCK-interacting kinase), IKKε (I-kappa-B kinase epsilon) and TBK1 (TANK-binding kinase 1) inhibitor; the pyrazole derivative according to the present invention effectively inhibits TNIK, IKKε and TBK1, and thus is useful not only as an anticancer agent for the treatment of various cancers including colorectal cancer, breast cancer, CNS cancer, colon cancer, non-small cell lung cancer, kidney cancer, prostate cancer, ovarian cancer, uterus cancer, stomach cancer, liver cancer, skin cancer, lung cancer, brain cancer, bladder cancer, esophageal cancer, pancreatic cancer, thyroid cancer, head and neck cancer, squamous cell carcinoma, osteosarcoma, B-cell or T-cell lymphoma, acute or chronic leukemia and multiple myeloma, but as a therapeutic agent for chronic inflammation.

A compound selected from the group consisting of:

(1) N-benzyl-3-(4-fluorobenzamido)-1H-indazole-5-carboxamide;
(2) N-(furan-2-yl-methyl)-3-(4-methoxybenzamido)-1H-indazole-5-carboxamide;
(3) 3-(4-methoxybenzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(4) 3-(4-methoxybenzamido)-N-methyl-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(5) 4-methoxy-N-(5-(4,5,6,7-tetrahydrothieno[2,3-c]pyridine-6-carbonyl)-1H-indazol-3-yl)benzamide
(6) 3-(4-(methylthio)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(7) 3-(1-methyl-1H-pyrazole-4-carboxamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(8) 3-(5-methoxypicolinamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide hydrochloride;
(9) 3-(2-methoxynicotinamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(10) 3-(4-tert-butylbenzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(11) 4-methoxy-N-(5-((thiophen-2-ylmethyl)amino)-1H-indazol-3-yl)benzamide;
(13) 3-benzamido-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(14) 3-(4-fluorobenzamido)-N-(1-(thiophen-2-yl)ethyl)-1H-indazole-5-carboxamide;
(15) 3-(4-fluorobenzamido)-N-(1-(thiophen-2-yl)cyclopropyl)-1H-indazole-5-carboxamide;
(16) N-(1-cyanocyclopropyl)-3-(4-fluorobenzamido)-1H-indazole-5-carboxamide;
(17) 3-(4-fluorobenzamido)-N-(1-(thiophen-2-yl)propyl)-1H-indazole-5-carboxamide;
(18) 3-(4-fluorobenzamido)-N-(1-(thiophen-2-yl)butyl)-1H-indazole-5-carboxamide;
(19) 3-(4-fluorobenzamido)-N-((5-methylthiophen-2-yl)methyl)-1H-indazole-5-carboxamide;
(20) 3-(4-fluorobenzamido)-N-(2-phenylpropan-2-yl)-1H-indazole-5-carboxamide;
(21) 3-(4-fluorobenzamido)-N-(4-(trifluoromethyl)benzyl)-1H-indazole-5-carboxamide;
(22) N-(cyclohexylmethyl)-3-(4-fluorobenzamido)-1H-indazole-5-carboxamide;
(23) N-(cyclopropylmethyl)-3-(4-fluorobenzamido)-1H-indazole-5-carboxamide;
(24) N-butyl-3-(4-fluorobenzamido)-1H-indazole-5-carboxamide;
(25) 3-(4-fluorobenzamido)-N-isopentyl-1H-indazole-5-carboxamide;
(26) N-((1,2,4-oxadiazol-3-yl)methyl)-3-(4-fluorobenzamido)-1H-indazole-5-carboxamide;
(27) 3-(4-fluorobenzamido)-N-(thiazol-5-ylmethyl)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(28) 3-(4-fluorobenzamido)-N-(pyridin-2-ylmethyl)-1H-indazole-5-carboxamide2,2,2-trifluoroacetate;
(29) 3-(4-fluorobenzamido)-N-(pyridin-4-ylmethyl)-1H-indazole-5-carboxamide;
(30) N-(cyclopropyl(thiophen-2-yl)methyl)-3-(4-fluorobenzamido)-1H-indazole-5-carboxamide;
(33) 3-(4-fluorobenzamido)-N-(3-methyl-1-(thiophen-2-yl)butyl)-1H-indazole-5-carboxamide;
(34) 3-(4-fluorobenzamido)-N-(2-(thiophen-2-yl)butan-2-yl)-1H-indazole-5-carboxamide;
(35) 3-(2,4-difluorobenzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(36) 3-(4-fluorobenzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(37) 3-(4-fluorobenzamido)-N-(1-phenylethyl)-1H-indazole-5-carboxamide;
(38) 3-(4-fluorobenzamido)-N-(1-phenylpropyl)-1H-indazole-5-carboxamide;
(39) 3-(phenylsulfonamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(40) N-benzyl-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(41) N-(1-phenylpropyl)-3-(4-(piperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(42) N-methyl-3-(4-morpholinobenzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(43) 3-(4-morpholinobenzamido)-N-(1-(thiophen-2-yl)ethyl)-1H-indazole-5-carboxamide;
(44) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-(thiophen-2-yl)ethyl)-1H-indazole-5-carboxamide;
(45) N-(2-hydroxy-1-(thiophen-2-yl)ethyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(46) 3-(4-morpholinobenzamido)-N-(thiophen-3-ylmethyl)-1H-indazole-5-carboxamide;
(47) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(thiophen-3-ylmethyl)-1H-indazole-5-carboxamide;
(48) 3-(4-morpholinobenzamido)-N-(1-(thiophen-2-yl)cyclopropyl)-1H-indazole-5-carboxamide;
(49) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-(thiophen-2-yl)cyclopropyl)-1H-indazole-5-carboxamide;
(50) N-(furan-2-ylmethyl)-3-(4-morpholinobenzamido)-1H-indazole-5-carboxamide;
(51) N-(furan-2-ylmethyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(52) 3-(4-morpholinobenzamido)-N-(1-(pyridin-3-yl)ethyl)-1H-indazole-5-carboxamide;
(53) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-(pyridin-3-yl)ethyl)-1H-indazole-5-carboxamide;
(54) 3-(4-morpholinobenzamido)-N-(1-(thiophen-2-yl)propyl)-1H-indazole-5-carboxamide;
(55) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-(thiophen-2-yl)propyl)-1H-indazole-5-carboxamide;
(56) 3-(4-morpholinobenzamido)-N-(pyridin-3-ylmethyl)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(57) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(pyridin-3-ylmethyl)-1H-indazole-5-carboxamide bis(2,2,2-trifluoroacetate);
(58) 3-(4-morpholinobenzamido)-N-(1-(thiophen-2-yl)butyl)-1H-indazole-5-carboxamide;
(59) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-(thiophen-2-yl)butyl)-1H-indazole-5-carboxamide;
(60) N-((5-methylthiophen-2-yl)methyl)-3-(4-morpholinobenzamido)-1H-indazole-5-carboxamide;
(61) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-((5-methylthiophen-2-yl)methyl)-1H-indazole-5-carboxamide;
(62) 3-(4-morpholinobenzamido)-N-(2-phenylpropan-2-yl)-1H-indazole-5-carboxamide;
(63) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(2-phenylpropan-2-yl)-1H-indazole-5-carboxamide;
(64) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(2-phenylpropan-2-yl)-1H-indazole-5-carboxamide hydrochloride;
(65) 3-(4-morpholinobenzamido)-N-(4-(trifluoromethyl)benzyl)-1H-indazole-5-carboxamide;
(66) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(4-(trifluoromethyl)benzyl)-1H-indazole-5-carboxamide;
(67) 3-(4-morpholinobenzamido)-N-(1-phenylcyclopropyl)-1H-indazole-5-carboxamide;
(68) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-phenylcyclopropyl)-1H-indazole-5-carboxamide;
(69) N-((2-methylpyridin-4-yl)methyl)-3-(4-morpholinobenzamido)-1H-indazole-5-carboxamide;
(70) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-((2-methylpyridin-4-yl)methyl)-1H-indazole-5-carboxamide;
(71) 3-(4-morpholinobenzamido)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)-1H-indazole-5-carboxamide;
(72) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl)-1H-indazole-5-carboxamide;
(73) 3-(2-methyl-4-morpholinobenzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(74) 3-(2-methyl-4-(4-methylpiperazin-1-yl)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(75) 3-(3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazol-5-yl)-3-oxo-2-(thiophen-2-yl)propanoic acid;
(76) (S)-3-(4-(3-methylpiperazin-1-yl)benzamido)-N-(1-phenylcyclopropyl)-1H-indazole-5-carboxamide;
(77) (R)-3-(4-(3-methylpiperazin-1-yl)benzamido)-N-(1-phenylcyclopropyl)-1H-indazole-5-carboxamide;
(78) 3-(3-methyl-4-morpholinobenzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(79) 3-(3-methyl-4-(4-methylpiperazin-1-yl)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(80) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-(thiophen-3-yl)ethyl)-1H-indazole-5-carboxamide;
(81) N-(1-(furan-2-yl)ethyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(82) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-(thiazol-2-yl)ethyl)-1H-indazole-5-carboxamide;
(83) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-(thiazol-5-yl)ethyl)-1H-indazole-5-carboxamide;
(84) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-(thiazol-2-yl)propyl)-1H-indazole-5-carboxamide;
(85) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(pyridin-2-ylmethyl)-1H-indazole-5-carboxamide bis(2,2,2-trifluoroacetate);
(86) 3-(4-morpholinobenzamido)-N-(pyridin-2-ylmethyl)-1H-indazole-5-carboxamide;
(87) N-(cyclohexylmethyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(88) N-(cyclohexylmethyl)-3-(4-morpholinobenzamido)-1H-indazole-5-carboxamide;
(89) 3-(4-(3,5-dimethylpiperazin-1-yl)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(90) N-(cyclopentylmethyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(91) N-(cyclopentylmethyl)-3-(4-morpholinobenzamido)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(92) 3-(4-(2,6-dimethylmorpholino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(93) N-(4-hydroxybutan-2-yl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(94) N-((1H-1,2,3-triazol-4-yl)methyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(95) 3-(4-(3,5-dimethylpiperazin-1-yl)benzamido)-N-(1-(thiophen-2-yl)propyl)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(96) 3-(4-(2,6-dimethylmorpholino)benzamido)-N-(1-(thiophen-2-yl)propyl)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(97) 3-(4-((S)-3-methylpiperazin-1-yl)benzamido)-N-(1-(thiophen-2-yl)propyl)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(98) 3-(4-((R)-3-methylpiperazin-1-yl)benzamido)-N-(1-(thiophen-2-yl)propyl)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(99) 3-(4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamido)-N-(1-(thiophen-2-yl)propyl)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(100) N-((3-methyl-1,2,4-oxadiazol-5-yl)methyl)-3-(4-morpholinobenzamido)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(101) N-((3-methyl-1,2,4-oxadiazol-5-yl)methyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(102) 3-(4-(piperazin-1-yl)benzamido)-N-(1-(thiophen-2-yl)propyl)-1H-indazole-5-carboxamide;
(103) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(thiazol-2-ylmethyl)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(104) 3-(4-morpholinobenzamido)-N-(thiazol-2-ylmethyl)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(105) N-((1,2,4-oxadiazol-3-yl)methyl)-3-(4-morpholinobenzamido)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(106) N-(cyclobutylmethyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(107) 3-(4-(3,3-dimethylpiperazin-1-yl)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(108) 3-(4-(4-hydroxypiperidin-1-yl)benzamido)-N-(1-(thiophen-2-yl)propyl)-1H-indazole-5-carboxamide;
(109) 3-(4-(4-ethylpiperazin-1-yl)benzamido)-N-(1-(thiophen-2-yl)propyl)-1H-indazole-5-carboxamide;
(110) 3-(4-(4-methoxypiperidin-1-yl)benzamido)-N-(1-(thiophen-2-yl)propyl)-1H-indazole-5-carboxamide;
(111) (S)-3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-(thiophen-2-yl)propyl)-1H-indazole-5-carboxamide;
(112) (R)-3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-(thiophen-2-yl)propyl)-1H-indazole-5-carboxamide;
(113) N-butyl-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(114) N-isopentyl-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(115) N-butyl-3-(4-morpholinobenzamido)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(116) N-isopentyl-3-(4-morpholinobenzamido)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(117) (S)-3-(4-(3-methylpiperazin-1-yl)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(118) N-((1,2,4-oxadiazol-3-yl)methyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(119) N-((1H-1,2,3-triazol-4-yl)methyl)-3-(4-morpholinobenzamido)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(120) 3-(4-morpholinobenzamido)-N-(pyridin-4-ylmethyl)-1H-indazole-5-carboxamide;
(121) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(pyridin-4-ylmethyl)-1H-indazole-5-carboxamide;
(122) N-(cyclopropyl(thiophen-2-yl)methyl)-3-(4-morpholinobenzamido)-1H-indazole-5-carboxamide;
(125) N-(cyclopropyl(thiophen-2-yl)methyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(126) N-(cyclopropyl(thiophen-2-yl)methyl)-3-(4-(piperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(127) 3-(4-morpholinobenzamido)-N-(1-(pyridin-2-yl)ethyl)-1H-indazole-5-carboxamide;
(128) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-(pyridin-2-yl)ethyl)-1H-indazole-5-carboxamide;
(129) N-(3-methyl-1-(thiophen-2-yl)butyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(130) N-(3-methyl-1-(thiophen-2-yl)butyl)-3-(4-morpholinobenzamido)-1H-indazole-5-carboxamide;
(131) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(2-(thiophen-2-yl)butan-2-yl)-1H-indazole-5-carboxamide;
(132) 3-(4-morpholinobenzamido)-N-(1-(pyridin-4-yl)ethyl)-1H-indazole-5-carboxamide;
(133) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-(pyridin-4-yl)ethyl)-1H-indazole-5-carboxamide;
(134) 3-(4-morpholinobenzamido)-N-(2-(thiophen-2-yl)propan-2-yl)-1H-indazole-5-carboxamide;
(135) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(2,2,2-trifluoro-1-(thiophen-2-yl)ethyl)-1H-indazole-5-carboxamide;
(136) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(2-(thiophen-2-yl)propan-2-yl)-1H-indazole-5-carboxamide;
(137) (S)-3-(4-(3-methylpiperazin-1-yl)benzamido)-N-(2-(thiophen-2-yl)propan-2-yl)-1H-indazole-5-carboxamide;
(138) 3-(4-morpholinobenzamido)-N-(2,2,2-trifluoro-1-(thiophen-2-yl)ethyl)-1H-indazole-5-carboxamide;
(139) N-(cyclopropyl(pyridin-2-yl)methyl)-3-(4-morpholinobenzamido)-1H-indazole-5-carboxamide;
(140) N-(cyclopropyl(pyridin-2-yl)methyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(141) 4-(4-methylpiperazin-1-yl)-N-(5-(2-(thiophen-2-yl)acetamido)-1H-indazol-3-yl)benzamide;
(142) N-(cyclopropyl(pyridin-3-yl)methyl)-3-(4-morpholinobenzamido)-1H-indazole-5-carboxamide;
(143) N-(cyclopropyl(pyridin-3-yl)methyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(144) 4-morpholino-N-(5-(2-(thiophen-2-yl)acetamido)-1H-indazol-3-yl)benzamide;
(145) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(2-(thiophen-3-yl)propan-2-yl)-1H-indazole-5-carboxamide;
(146) N-((5-chlorothiophen-2-yl)methyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(147) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-(thiophen-2-yl)cyclohexyl)-1H-indazole-5-carboxamide;
(148) 3-(4-morpholinobenzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(149) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(150) 3-(4-((2-methoxyethyl)amino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(151) 3-(4-((3-methoxypropyl)amino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(152) 3-(4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(153) 3-(4-((2-morpholinoethyl)amino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(154) 3-(4-((3-(dimethylamino)propyl)amino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(155) 3-(4-(methyl(2-(methylamino)ethyl)amino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(156) 3-(3-morpholinobenzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(157) 3-(4-(((tetrahydrofuran-2-yl)methyl)amino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(158) 3-(4-((2-(dimethylamino)ethyl)amino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(159) 3-(4-(isopentylamino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(160) 3-(4-((2-(tetrahydro-2H-pyran-4-yl)ethyl)amino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(161) 3-(4-(hexylamino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(162) 3-(4-(cyclohexylamino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(163) 3-(4-(cyclopentylamino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(164) 3-(4-(cycloheptylamino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(165) 3-(4-(cyclooctylamino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(166) 3-(4-((cyclohexylmethyl)amino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(167) 3-(4-((2-(cyclohex-1-en-1-yl)ethyl)amino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(168) 3-(2,4-dimorpholinobenzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(169) 3-(4-((2-(1H-pyrrol-1-yl)ethyl)amino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(170) 3-(2-fluoro-4-(4-methylpiperazin-1-yl)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(171) 3-(4-(piperazin-1-yl)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(172) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(oxazol-5-ylmethyl)-1H-indazole-5-carboxamide;
(173) N-(isoxazol-3-ylmethyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(174) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(thiazol-4-ylmethyl)-1H-indazole-5-carboxamide;
(175) (R)-3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-phenylethyl)-1H-indazole-5-carboxamide;
(176) (S)-3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-phenylethyl)-1H-indazole-5-carboxamide;
(177) N-benzyl-3-(4-morpholinobenzamido)-1H-indazole-5-carboxamide;
(178) N-(isoxazol-5-ylmethyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(179) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-phenylethyl)-1H-indazole-5-carboxamide;
(180) 3-(4-morpholinobenzamido)-N-(1-phenylethyl)-1H-indazole-5-carboxamide;
(181) N-(1-phenylethyl)-3-(4-(piperazin-1-yl)benzamido)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(182) 3-(4-(3,5-dimethylpiperazin-1-yl)benzamido)-N-(1-phenylethyl)-1H-indazole-5-carboxamide;
(183) 3-(4-(2,6-dimethylmorpholino)benzamido)-N-(1-phenylethyl)-1H-indazole-5-carboxamide;
(184) 3-(4-((S)-3-methylpiperazin-1-yl)benzamido)-N-(1-phenylethyl)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(185) 3-(4-((R)-3-methylpiperazin-1-yl)benzamido)-N-(1-phenylethyl)-1H-indazole-5-carboxamide 2,2,2-trifluoroacetate;
(186) 3-(4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamido)-N-(1-phenylethyl)-1H-indazole-5-carboxamide;
(187) 3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-phenylpropyl)-1H-indazole-5-carboxamide;
(188) 3-(4-morpholinobenzamido)-N-(1-phenylpropyl)-1H-indazole-5-carboxamide;
(189) N-(4-fluorobenzyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(190) (S)-3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-phenylpropyl)-1H-indazole-5-carboxamide;
(191) (R)-3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-phenylpropyl)-1H-indazole-5-carboxamide;
(192) (R)-3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-phenylpropyl)-1H-indazole-5-carboxamide hydrochloride;
(193) (S)-3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-phenylbutyl)-1H-indazole-5-carboxamide;
(194) (R)-3-(4-(4-methylpiperazin-1-yl)benzamido)-N-(1-phenylbutyl)-1H-indazole-5-carboxamide;
(195) N-(3-fluorobenzyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(196) N-(2-fluorobenzyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(197) N-(cyclopropyl(phenyl)methyl)-3-(4-(4-methylpiperazin-1-yl)benzamido)-1H-indazole-5-carboxamide;
(198) tert-butyl 4-(4-((5-((thiophen-2-ylmethyl)carbamoyl)-1H-indazol-3-yl)carbamoyl)phenyl)-3,6-tetrahydropyridine-1(2H)-carboxylate;
(199) 3-(4-(1,2,3,6-tetrahydropyridin-4-yl)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(200) 3-(4-hydroxybenzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(201) 3-(4-(2-morpholinoethoxy)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(202) tert-butyl 3-(4-nitrobenzamido)-5-((thiophen-2-ylmethyl)carbamoyl)-1H-indazole-1-carboxylate;
(203) 3-(4-nitrobenzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(204) 3-(3-nitrobenzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(205) 3-(4-aminobenzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(206) 3-(4-(cyclobutanecarboxamido)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(207) N-(thiophen-2-ylmethyl)-3-(4-(1-(trifluoromethyl)cyclopropanecarboxamido)benzamido)-1H-indazole-5-carboxamide;
(208) 3-(4-(3-oxocyclobutanecarboxamido)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(209) 3-(4-(4-acetylpiperazin-1-yl)benzamido)-N-(1-(thiophen-3-yl)propyl)-1H-indazole-5-carboxamide;
(210) tert-butyl (S)-2-((4-((5-((thiophen-2-ylmethyl)carbamoyl)-1H-indazol-3-yl)carbamoyl)phenyl)carbamoyl)pyrrolidine-1-carboxylate;
(211) 3-(4-acetamidobenzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(212) 3-(4-(1H-imidazol-1-yl)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(213) 3-(4-((1-methylpiperidin-4-yl)amino)benzamido)-N-(thiophen-2-ylmethyl)-1H-indazole-5-carboxamide;
(214) 3-(4-fluorobenzamido)-N-(1-(pyridin-4-yl)ethyl)-1H-indazole-5-carboxamide;
(215) 3-(4-fluorobenzamido)-N-(2-(thiophen-2-yl)propan-2-yl)-1H-indazole-5-carboxamide;
(216) 3-(4-fluorobenzamido)-N-(1-(pyridin-2-yl)cyclopropyl)-1H-indazole-5-carboxamide;
(217) 3-(4-fluorobenzamido)-N-(1-(pyridin-3-yl)cyclopropyl)-1H-indazole-5-carboxamide;
(218) N-(5-(5-methyloxazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)-4-morpholinobenzamide;
(219) N-(5-(5-methylthiazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)-4-morpholinobenzamide;
(220) N-(5-(5-methyloxazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)benzamide;
(221) 4-fluoro-N-(5-(5-methyloxazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)benzamide;
(222) 4-methoxy-N-(5-(5-methyloxazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)benzamide;
(223) 4-(dimethylamino)-N-(5-(5-methyloxazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)benzamide;
(224) N-(5-(5-methyloxazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
(225) N-(5-(5-methyloxazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)-4-(4-methylpiperazin-1-yl)benzamide;
(226) N-(5-(5-methyloxazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)-4-((2-(pyrrolidin-1-yl)ethyl)amino)benzamide;
(227) N-(5-(5-methyloxazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)-4-((2-morpholinoethyl)amino)benzamide;
(228) 4-((2-hydroxyethyl)amino)-N-(5-(5-methyloxazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)benzamide;
(229) 4-((2-methoxyethyl)amino)-N-(5-(5-methyloxazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)benzamide;
(230) 3-fluoro-N-(5-(5-methyloxazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)benzamide;
(231) methyl 3-(4-methoxyphenyl)-1H-thieno[3,2-c]pyrazole-5-carboxylate;
(232) N-ethyl-3-(4-methoxyphenyl)-1H-thieno[3,2-c]pyrazole-5-carboxamide;
(233) N-isopropyl-3-(4-methoxyphenyl)-1H-thieno[3,2-c]pyrazole-5-carboxamide;
(234) methyl 3-(4-(dimethylamino)phenyl)-1H-thieno[3,2-c]pyrazole-5-carboxylate;
(235) 2-(3-(4-methoxyphenyl)-1H-thieno[3,2-c]pyrazol-5-yl)-5-methyloxazole;
(236) methyl 3-phenyl-1H-thieno[3,2-c]pyrazole-5-carboxylate;
(237) 3-(4-(dimethylamino)phenyl)-N-ethyl-1H-thieno[3,2-c]pyrazole-5-carboxamide;
(238) N-ethyl-3-phenyl-1H-thieno[3,2-c]pyrazole-5-carboxamide;
(239) methyl 3-(4-fluorophenyl)-1H-thieno[3,2-c]pyrazole-5-carboxylate;
(240) N-ethyl-3-(4-fluorophenyl)-1H-thieno[3,2-c]pyrazole-5-carboxamide;
(241) N-ethyl-3-(4-morpholinophenyl)-1H-thieno[3,2-c]pyrazole-5-carboxamide;
(242) 3-(4-fluorophenyl)-N-(2-morpholinoethyl)-1H-thieno[3,2-c]pyrazole-5-carboxamide;
(243) 4-(4-(5-(5-methyloxazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)phenyl)morpholine;
(244) 4-(4-(5-(5-ethyloxazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)phenyl)morpholine;
(245) methyl 3-(4-acetamidophenyl)-1H-thieno[3,2-c]pyrazole-5-carboxylate;
(246) 2-(3-(4-fluorophenyl)-1H-thieno[3,2-c]pyrazol-5-yl)-5-methyloxazole;
(247) 3-(4-fluorophenyl)-5-(5-methylthiazol-2-yl)-1H-thieno[3,2-c]pyrazole;
(248) (3-(4-morpholinophenyl)-1H-thieno[3,2-c]pyrazol-5-yl)(pyrrolidin-1-yl)methanone;
(249) methyl 3-(4-(2-morpholinoethoxy)phenyl)-1H-thieno[3,2-c]pyrazole-5-carboxylate;
(250) 4-(2-(4-(5-(5-methyloxazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)phenoxy)ethyl)morpholine;
(251) 4-(dimethylamino)-N-(5-(5-methylthiazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)benzamide;
(252) N-(5-(5-ethylthiazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)-4-morpholinobenzamide;
(253) N-(5-(5-methylthiazol-2-yl)-1H-thieno[3,2-c]pyrazol-3-yl)-4-((2-(piperidin-1-yl)ethyl)amino)benzamide;
and
(254) methyl 3-(4-morpholinophenyl)-1H-thieno[3,2-c]pyrazole-5-carboxylate,
or pharmaceutically acceptable salt, a hydrate, or a solvate thereof.

248 more elements

Pyrazole derivatives as TNIK, IKKϵ and TBK1 inhibitor and pharmaceutical composition comprising same

Life of this patent

Pyrazole derivatives as TNIK, IKKϵ and TBK1 inhibitor and pharmaceutical composition comprising same

Life of this patent

Abstract

Claims1