Patent NZ-600084-A (NZ)
Title: Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
Inventor: BRUNCKO MILAN
IPC: A61K31/404
Filed: 2010-06-01
Abstract: 600084 Disclosed are 2-(1H-indol-5-yloxy) / 2-(1H-indazol-4-yloxy) / 2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-4-yl)oxy and 2-[(6-amino-5-chloropyridin-3-yl)oxy] N-({ pyridin-3-yl / phenyl} sulfonyl)benzamide derivatives as represented by the general formula (I), wherein the compounds are N-({ 3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]phenyl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide; N-({ 3-chloro-4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]phenyl} sulfonyl)-4-(4-{ [4-(4-chlorophenyl)-6,6-dimethyl-5,6-dihydro-2H-pyran-3-yl]methyl} piperazin-1-yl)-2-[(6-fluoro-1Hindol-5-yl)oxy]benzamide; N-({ 5-chloro-6-[(trans-4-hydroxycyclohexyl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]benzamide; N-({ 5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]benzamide; tert-butyl 5-[(4-{ 4-[({ 5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]pyridin-3-yl} sulfonyl)carbamoyl]-3-[(6-fluoro-1H-indol-5-yl)oxy]phenyl} piperazin-1-yl)methyl]-4-(4-chlorophenyl)-3,6-dihydropyridine-1(2H)-carboxylate; N-({ 5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [4-(4-chlorophenyl)-1-(1,3-difluoropropan-2-yl)-1,2,5,6-tetrahydropyridin-3-yl]methyl} piperazin-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]benzamide; 4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]-N-[(4-{ [(4-fluorotetrahydro-2H-pyran-4-yl)methyl]amino} -3-nitrophenyl)sulfonyl]benzamide; N-({ 5-chloro-6-[(trans-4-hydroxycyclohexyl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-[(7-fluoro-1H-indazol-4-yl)oxy]benzamide; N-({ 5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-[(7-fluoro-1H-indazol-4-yl)oxy]benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-{ [3-nitro-4-({ [4-(oxetan-3-yl)morpholin-2-yl]methyl} amino)phenyl]sulfonyl} benzamide; 4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-[(6-fluoro-1H-indol-5-yl)oxy]-N-{ [3-nitro-4-({ [4-(oxetan-3-yl)morpholin-2-yl]methyl} amino)phenyl]sulfonyl} benzamide; 4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-[(7-fluoro-1H-indazol-4-yl)oxy]-N-[(4-{ [(4-fluorotetrahydro-2H-pyran-4-yl)methyl]amino} -3-nitrophenyl)sulfonyl]benzamide; N-({ 5-chloro-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-[(6-fluoro-1Hindazol-4-yl)oxy]benzamide; 4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-{ [5-chloro-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl} -2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-4-yl)oxy]benzamide; 4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-({ 4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3-nitrophenyl} sulfonyl)-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-4-yl)oxy]benzamide; 4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-[(4-{ [(trans-4-methoxycyclohexyl)methyl]amino} -3-nitrophenyl)sulfonyl]-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-4-yl)oxy]benzamide; 2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-[(4-{ [(4-fluorotetrahydro-2H-pyran-4-yl)methyl]amino} -3-nitrophenyl)sulfonyl]benzamide; 2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-({ 4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3-nitrophenyl} sulfonyl)benzamide; 2-[(3-amino-1H-indazol-4-yl)oxy]-N-({ 5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)benzamide; 2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-({ 3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl} sulfonyl)benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-[(4-{ [4-fluoro-1-(oxetan-3-yl)piperidin-4-yl]methoxy} -3-nitrophenyl)sulfonyl]benzamide; 4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-[(6-fluoro-1H-indazol-4-yl)oxy]-N-({ 4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]-3-nitrophenyl} sulfonyl)benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-[(4-{ [(trans-4-hydroxy-4-methylcyclohexyl)methyl]amino} -3-nitrophenyl)sulfonyl]benzamide; 2-[(3-amino-1H-indazol-4-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-[(4-{ [(trans-4-methoxycyclohexyl)methyl]amino} -3-nitrophenyl)sulfonyl]benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-({ 4-[(cis-4-hydroxy-4-methylcyclohexyl)methoxy]-3-nitrophenyl} sulfonyl)benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-[(4-{ [(cis-4-hydroxy-4-methylcyclohexyl)methyl]amino} -3-nitrophenyl)sulfonyl]benzamide; 4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-{ [3-chloro-4-(tetrahydro-2H-pyran-4-ylmethoxy)phenyl]sulfonyl} -2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-4-yl)oxy]benzamide; 4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-[(4-{ [(4-cyclopropylmorpholin-2-yl)methyl]amino} -3-nitrophenyl)sulfonyl]-2-[(3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-4-yl)oxy]benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-{ [3-nitro-4-(2-oxaspiro[3.5]non-7-ylmethoxy)phenyl]sulfonyl} benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-({ 4-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]-3-nitrophenyl} sulfonyl)benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-{ [4-({ [(2S)-4-cyclopropylmorpholin-2-yl]methyl} amino)-3-nitrophenyl]sulfonyl} benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({ 5-chloro-6-[(trans-1-fluoro-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-N-({ 5-chloro-6-[(cis-1-fluoro-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)benzamide; 2-[(3-amino-1H-indazol-4-yl)oxy]-N-({ 5-chloro-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)benzamide; N-({ 5-chloro-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl} sulfonyl)-2-[(3-chloro-1H-indazol-4-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-[(4-{ [(cis-4-ethyl-4-hydroxycyclohexyl)methyl]amino} -3-nitrophenyl)sulfonyl]benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-{ [3-nitro-4-({ [(2S)-4-(oxetan-3-yl)morpholin-2-yl]methyl} amino)phenyl]sulfonyl} benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-({ 5-nitro-6-[(tetrahydro-2H-pyran-4-ylmethyl)amino]pyridin-3-yl} sulfonyl)benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-({ 3-nitro-4-[(2-oxaspiro[3.5]non-7-ylmethyl)amino]phenyl} sulfonyl)benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-{ [4-({ [trans-4-(morpholin-4-yl)cyclohexyl]methyl} amino)-3-nitrophenyl]sulfonyl} benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-[(4-{ [cis-4-(morpholin-4-yl)cyclohexyl]amino} -3-nitrophenyl)sulfonyl]benzamide; 4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-({ 5-cyano-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl} sulfonyl)-2-[(6-fluoro-1Hindazol-4-yl)oxy]benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-{ [4-({ [4-({ [4-(methoxymethyl)cyclohexyl]methyl} amino)-3-nitrophenyl]sulfonyl} amino)-3-nitrophenyl]sulfonyl} benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-[(3-nitro-4-{ [(3R)-1-(oxetan-3-yl)pyrrolidin-3-yl]amino} phenyl)sulfonyl]benzamide; 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-[(3-nitro-4-{ [(3S)-1-(oxetan-3-yl)pyrrolidin-3-yl]amino} phenyl)sulfonyl]benzamide; N-[4-({ 2-[(6-amino-5-chloropyridin-3-yl)oxy]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)benzoyl} sulfamoyl)-2-nitrophenyl]morpholine-4-carboxami