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92. 发明专利

ES2487617T3 Agentes inductores de la apoptosis para el tratamiento del cáncer y enfermedades inmunes y autoinmunes 未知
公开(公告)号：ES2487617T3
公开(公告)日：2014-08-22
申请号：ES10722500
申请日：2010-06-01
申请人： ABBVIE INC
发明人： BRUNCKO MILAN , DAI YUJIA , DING HONG , DOHERTY GEORGE A , ELMORE STEVEN W , HASVOLD LISA , HEXAMER LAURA , KUNZER AARON , MANTEI ROBERT A , MCCLELLAN WILLIAM J , PARK CHANG H , PARK CHEOL-MIN , PETROS ANDREW M , SONG XIAOHONG , SOUERS ANDREW J , SULLIVAN GERARD M , TAO ZHI-FU , WANG GARY T , WANG LE , WANG XILU , WENDT MICHAEL D , HANSEN TODD M
IPC分类号： C07D209/08 , C07D211/58 , C07D213/74 , C07D213/84 , C07D231/56 , C07D235/06 , C07D277/24 , C07D309/04 , C07D401/14 , C07D403/12 , C07D405/12 , C07D405/14 , C07D413/12 , C07D417/12 , C07D471/04
摘要： Un compuesto, o una de sus sales terapéuticamente aceptables, donde el compuesto se seleccionado entre: . N-({3-cloro-4-[(4-fluorotetrahidro-2H-piran-4-il)metoxi]fenil}sulfonil)-4-(4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1- en-1-il]metil}piperazin-1-il)-2-[(6-fluoro-1H-indol-5-il)oxi]benzamida; N-({3-cloro-4-[(4-fluorotetrahidro-2H-piran-4-il)metoxi]fenil}sulfonil)-4-(4-{[4-(4-clorofenil)-6,6-dimetil-5,6-dihidro -2H-piran-3-il]metil}piperazin-1-il)-2-[(6-fluoro-1H-indol-5-il)oxi]benzamida; N-({5-cloro-6-[(trans-4-hidroxiciclohexil)metoxi]piridin-3-il}sulfonil)-4-(4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-e n-1-il]metil}piperazin-1-il)-2-[(6-fluoro-1H-indazol-4-il)oxi]benzamida; N-({5-cloro-6-[(4-fluorotetrahidro-2H-piran-4-il)metoxi]piridin-3-il}sulfonil)-4-(4-{[2-(4-clorofenil)-4,4-dimetilcicloh ex-1-en-1-il]metil}piperazin-1-il)-2-[(6-fluoro-1H-indazol-4-il)oxi]benzamida; 5-[(4-{4-[({5-cloro-6-[(4-fluorotetrahidro-2H-piran-4-il)metoxi]piridin-3-il}sulfonil)carbamoil]-3-[(6-fluoro-1H-indol- 5-il)oxi]fenil}piperazin-1-il)metil]-4-(4-clorofenil)-3,6-dihidropiridina-1(2H)-carboxilato de terc-butilo; N-({5-cloro-6-[(4-fluorotetrahidro-2H-piran-4-il)metoxi]piridin-3-il}sulfonil)-4-(4-{[4-(4-clorofenil)-1-(1,3-difluoropr opan-2-il)-1,2,5,6-tetrahidropiridin-3-il]metil}piperazin-1-il)-2-[(6-fluoro-1H-indol-5-il)oxi]benzamida; 4-((4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-2-[(6-fluoro-1H-indazol-4-il)oxi]-N-[(4-{[( 4-fluorotetrahidro-2H-piran-4-il)metil]amino}-3-nitrofenil)sulfonil]benzamida; N-({5-cloro-6-[(trans-4-hidroxiciclohexil)metoxi]piridin-3-il}sulfonil)-4-(4-{[2-(4-chorofenil)-4,4-dimetilciclohex-1- en-1-il]metil}piperazin-1-il)-2-[(7-fluoro-1H-indazol-4-il)oxi]benzamida; N-({5-cloro-6-[(4-fluorotetrahidro-2H-piran-4-il)metoxi]piridin-3-il}sulfonil)-4-(4-{[2-(4-clorofenil)-4,4-dimetilcicloh ex-1-en-1-il]metil}piperazin-1-il)-2-[(7-fluoro-1H-indazol-4-il)oxi]benzamida; 2-[((6-amino-5-cloropiridin-3-il)oxi]-4-(4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-N-{[3- nitro-4-({[4-(oxetan-3-il)morfolin-2-il]metil}amino)fenil]sulfonil}benzamida; 4-((4-{[2-(4-clorofenil)-4,4-dimetiloyclohex-1-en-1-il]metil}piperazin-1-il)-2-[(6-fluoro-1H-indol-5-il)oxi]-N-{[3-nitr o-4-({[4-(oxetan-3-il)morfolin-2-il]metil}amino)fenil]sulfonil}benzamida; 4-((4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-2-[(7-fluoro-1H-indazol-4-il)oxi]-N-[(4-{[( 4-fluorotetrahidro-2H-piran-4-il)metil]amino}-3-nitrofenil)sulfonil]benzamida; N-({5-cloro-6-[(trans-4-hidroxi-4-metilciclohexil)metoxi]piridin-3 -il}sulfonil)-4-(4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-2-[(6-fluoro-1H-indazol-4-il)ox i]benzamida; 4-((4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-N-{[5-cloro-6-(tetrahidro-2H-piran-4-ilm etoxi)piridin-3-il]sulfonil}-2-[(3-metil-2-oxo-2,3-dihidro-1H-bencimidazol-4-il)oxi]benzamida; 4-((4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-N-({4-[(4-fluorotetrahidro-2H-piran-4-il) metoxi]-3-nitrofenil}sulfonil)-2-[(3-metil-2-oxo-2,3-dihidro-1H-bencimidazol-4-il)oxi]benzamida; 4-(4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-N;-[(4-{[(trans-4-metoxicy-clohexil)metil] amino}-3-nitrofenil)sulfonil]-2-[(3-metil-2-oxo-2,3-dihidro-1H-bencimidazol-4-il)oxi]benzamida; 2-[((3-amino-1H-indazol-4-il)oxi]-4-(4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-N-[(4-{[( 4-fluorotetrahidro-2H-piran-4-il)metil]amino}-3-nitrofenil)sulfonil]benzamida; 2-[((3-amino-1H-indazol-4-il)oxi]-4-(4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-N-({4-[( 4-fluorotetrahidro-2H-piran-4-il)metoxi]-3-nitrofenil}sulfonil)benzamida; 2-[((3-amino-1H-indazol-4-il)oxi]-N-({5-cloro-6-[(4-fluorotetrahidro-2H-piran-4-il)metoxi]piridin-3-il}sulfonil)-4-(4- {[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)benzamida; 2-[((3-amino-1H-indazol-4-il)oxi]-4-(4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-N-({3-ni 45 tro-4-[(tetrahidro-2H-piran-4-ilmetil)amino]fenil}sulfonil)benzamida; 2-[((6-amino-5-cloropiridin-3-il)oxi]-4-(4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-N-[(4- {[4-fluoro-1-(oxetan-3-il)piperidin-4-il]metoxi}-3-nitrofenil)sulfonil]benzamida; 4-((4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-2-[(6-fluoro-1H-indazol-4-il)oxi]-N-({4-[( 4-fluorotetrahidro-2H-piran-4-il)metoxi]-3-nitrofenil}sulfonil)benzamida; 2-[((6-amino-5-cloropiridin-3-il)oxi]-4-(4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-N-[(4- {[(trans-4-hidroxi-4-metilciclohexil)metil]amino}-3-nitrofenil)sulfonil]benzamida; 2-[((3-amino-1H-indazol-4-il)oxi]-4-(4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-N-[(4-{[( trans-4-metoxiciclohexil)metil]amino}-3-nitrofenil)sulfonil]benzamida; 2-[((6-amino-5-cloropiridin-3-il)oxi]-4-(4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-N-({4 -[(cis-4-hidroxi-4-metilciclohexil)metoxi]-3-nitrofenil}sulfonil)benzamida; 2-[((6-amino-5-cloropiridin-3-il)oxi]-4-(4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-N-[(4- {[(cis-4-hidroxi-4-metilciclohexil)metil]amino}-3-nitrofenil)sulfonil]benzamida; 4-((4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-N-{[3-cloro-4-(tetrahidro-2H-piran-4-ilm etoxi)fenil]sulfonil}-2-[(3-metil-2-oxo-2,3-dihidro-1H-bencimidazol-4-il)oxi]benzamida; 4-((4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-N-[(4-{[(4-ciclopropilmor-pholin-2-il)meti l]amino}-3-nitrofenil)sulfonil]-2-[(3-metil-2-oxo-2,3-dihidro-1H-bencimidazol-4-il)oxi]benzamida; 2-[((6-amino-5-cloropiridin-3-il)oxi]-4-(4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piper-azin-1-il)-N-{[3 -nitro-4-(2-oxaspiro[3.5]non-7-ilmetoxi)fenil]sulfonil}benzamida; 2-[((6-amino-5-cloropiridin-3-il)oxi]-4-(4-{[2-(4-clorofenil)-4,4-dimetilciclohex-1-en-1-il]metil}piperazin-1-il)-N-({4 -[(trans-4-hidroxi-4-metilciclohexil)metoxi]-3-nitrofenil}sulfonil)benzamida.

95. 发明专利

NZ599778A Sulfonamide derivatives as bcl-2-selective apoptosis-inducing agents for the treatment of cancer and immune diseases 未知
公开(公告)号：NZ599778A
公开(公告)日：2014-04-30
申请号：NZ59977810
申请日：2010-06-01
申请人： ABBVIE INC
发明人： BRUNCKO MILAN , DING HONG , DOHERTY GEORGE A , ELMORE STEVEN W , HASVOLD LISA , HEXAMER LAURA , KUNZER AARON , MANTEI ROBERT A , MCCLELLAN WILLIAM J , PARK CHANG H , PARK CHEOL-MIN , PETROS ANDREW M , SONG XIAOHONG , SOUERS ANDREW J , SULLIVAN GERARD M , TAO ZHI-FU , WANG GARY T , WANG LE , WANG XILU , WENDT MICHAEL D , HANSEN TODD M
IPC分类号： C07D405/12 , A61K31/404 , A61K31/416 , A61K31/4184 , A61K31/4192 , A61K31/496 , A61P35/00 , C07D209/32 , C07D211/96 , C07D213/64 , C07D215/20 , C07D217/16 , C07D231/56 , C07D235/08 , C07D235/26 , C07D249/04 , C07D249/18 , C07D295/125 , C07D295/14 , C07D295/155 , C07D309/14 , C07D401/12 , C07D405/14
摘要： 599778 Disclosed are 2-(1H-indazol-4-yloxy) / 2-(1H-benzimidazol-4-yloxy) and 2-(1H-benzotriazol-4-yloxy) N-({ pyridin-3-yl/phenyl} sulfonyl)benzamide derivatives, wherein the claimed compounds are selected from N-({ 5-chloro-6-[(4,4-difluorocyclohexyl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; N-({ 6-[(trans-4-carbamoylcyclohexyl)methoxy]-5-chloropyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; 4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-[(4-{ [(trans-4-cyanocyclohexyl)methyl]amino} -3-nitrophenyl)sulfonyl]-2-(1H-indazol-4-yloxy)benzamide; N-({ 5-chloro-6-[2-(1H-imidazol-1-yl)ethoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; N-({ 5-chloro-6-[(1-methyl-1H-imidazol-5-yl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; 4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-{ [5-fluoro-6-(tetrahydro-2H-pyran-4-ylmethoxy)pyridin-3-yl]sulfonyl} -2-(1H-indazol-4-yloxy)benzamide; N-{ [5-chloro-6-(1,4-dioxan-2-ylmethoxy)pyridin-3-yl]sulfonyl} -4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; N-({ 5-chloro-6-[(4,4-difluoro-1-hydroxycyclohexyl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; N-({ 5-chloro-6-[(2,2-difluorocyclopropyl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; N-({ 5-chloro-6-[(trans-4-cyanocyclohexyl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; N-({ 5-chloro-6-[(cis-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-(1H-indazol-4-yloxy)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-(1H-indazol-4-yloxy)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-(1Hindazol-4-yloxy)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-(trifluoromethyl)phenyl} sulfonyl)-2-(1Hindazol-4-yloxy)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-(1H-indazol-4-yloxy)benzamide; 2-(1H-benzimidazol-4-yloxy)-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)benzamide; 2-(1H-benzimidazol-4-yloxy)-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} benzamide; 4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-N-({ 3-cyano-4-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]phenyl} sulfonyl)-2-(1H-indazol-4-yloxy)benzamide; N-{ [3-chloro-4-(1,4-dioxan-2-ylmethoxy)phenyl]sulfonyl} -4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; 2-(1H-benzimidazol-4-yloxy)-N-[(5-chloro-6-{ [(2S)-4-cyclopropylmorpholin-2-yl]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-{ [(2S)-4-cyclopropylmorpholin-2-yl]methoxy} pyridin-3-yl)sulfonyl]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; methyl 2-{ [(4-{ [4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzoyl]sulfamoyl} -2-nitrophenyl)amino]methyl} morpholine-4-carboxylate; 2-{ [(4-{ [4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzoyl]sulfamoyl} -2-nitrophenyl)amino]methyl} -N-ethyl-Nmethylmorpholine-4-carboxamide; 2-{ [(4-{ [2-(1H-benzimidazol-4-yloxy)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)benzoyl]sulfamoyl} -2-nitrophenyl)amino]methyl} -N-ethyl-N-methylmorpholine-4-carboxamide; N-({ 5-chloro-6-[(trans-4-ethyl-4-hydroxycyclohexyl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; N-({ 5-chloro-6-[(cis-4-ethyl-4-hydroxycyclohexyl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; 5-chloro-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-(1Hindazol-4-yloxy)benzamide; 5-chloro-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]-2-(1Hindazol-4-yloxy)benzamide; 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)-2-(1Hindazol-4-yloxy)benzamide; 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)-2-(1H-indazol-4-yloxy)benzamide; 2-(1H-benzotriazol-4-yloxy)-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-(1H-benzotriazol-4-yloxy)-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-(1H-benzimidazol-4-yloxy)-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} benzamide; N-[(3-chloro-4-{ [4-fluoro-1-(oxetan-3-yl)piperidin-4-yl]methoxy} phenyl)sulfonyl]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; N-({ 5-chloro-6-[(cis-1-fluoro-4-hydroxycyclohexyl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; 2-(1H-benzotriazol-4-yloxy)-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; N-[(5-chloro-6-{ [(1R,2R,4R,5R)-5-hydroxy-5-methylbicyclo[2.2.1]hept-2-yl]methoxy} pyridin-3-yl)sulfonyl]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; N-({ 5-chloro-6-[(4-fluorotetrahydro-2H-pyran-4-yl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-5,5-difluorocyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; N-[(5-chloro-6-{ [4-fluoro-1-(oxetan-3-yl)piperidin-4-yl]methoxy} pyridin-3-yl)sulfonyl]-4-(4-{ [2-(4-chlorophenyl)-5,5-difluorocyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; 2-(1H-benzotriazol-4-yloxy)-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; 4-(4-{ [2-(4-chlorophenyl)-5,5-difluorocyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1Hindazol-4-yloxy)-N-({ 3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl} sulfonyl)benzamide; 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]-2-(1Hindazol-4-yloxy)benzamide; 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]-2-(1H-indazol-4-yloxy)benzamide; 2-(1H-benzotriazol-4-yloxy)-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; N-[(5-chloro-6-{ [4-fluoro-1-(oxetan-3-yl)piperidin-4-yl]methoxy} pyridin-3-yl)sulfonyl]-4-(4-{ [2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; 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} -2-(1Hindazol-4-yloxy)benzamide; 2-(1H-benzimidazol-4-yloxy)-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; N-({ 5-chloro-6-[(trans-4-hydroxy-4-methylcyclohexyl)methoxy]pyridin-3-yl} sulfonyl)-4-(4-{ [2-(4-chlorophenyl)-5,5-difluorocyclohex-1-en-1-yl]methyl} piperazin-1-yl)-2-(1H-indazol-4-yloxy)benzamide; 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)-2-(1H-indazol-4-yloxy)benzamide; 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} s

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