Details for Patent: 9,034,875

Title:	Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
Abstract:	Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein.
Inventor(s):	Doherty; George A. (Libertyville, IL), Elmore; Steven W. (Northbrook, IL), Hasvold; Lisa A. (Grayslake, IL), Souers; Andrew J. (Evanston, IL), Tao; Zhi-Fu (Gurnee, IL), Wang; Gary T. (Libertyville, IL), Wang; Le (Vernon Hills, IL), Mantei; Robert (Franklin, WI), Hansen; Todd M. (Grayslake, IL)
Assignee:	ABBVIE INC. (North Chicago, IL)
Filing Date:	Mar 14, 2013
Application Number:	13/831,184
Claims:	1. A method of treating lymphoblastic leukemia, in a patient, the method comprising administering to the patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of: methyl trans-4-{[(4-{[4-(4-[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]me- thyl piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzoyl]sulfamoyl- }-2-nitrophenyl)amino]methyl 1 cyclohexanecarboxylate; trans-4-{[(4-{[4-(4-[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]me- thyl}piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzoyl]sulfamoyl- }-2-nitrophenyl)amino]methyl}cyclohexanecarboxylic acid; N-(4-{[4-(4-[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzoyl]sulfamoyl}-2-- nitrophenyl)-4-cyanopiperidine-1-carboxamide; 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin- -1-yl)-N-}[4-({[cis-4-(methoxymethyl)cyclohexyl]methyl}amino)-3-nitropheny- l]sulfonyl}-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide; 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin- -1-yl)-N-{[4-({[trans-4-(methoxymethyl)cyclohexyl]methyl}amino)-3-nitrophe- nyl]sulfonyl}-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide; 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-N-{[1-(tetrahydro-2H- -pyran-4-ylmethyl)-1H-benzotriazol-5-yl]sulfonyl}benzamide; N-({5-chloro-6-[(2-oxo-1-oxa-3-azaspiro[4.5]dec-8-yl)methoxy}pyridin-3-yl- }sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl- }piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide; N-(4-{[4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}pi- perazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzoyl]sulfamoyl}-2-nit- rophenyl)-4-methoxypiperidine-1-carboxamide; N-({5-chloro-6-[(2-methyl-4,5,6,7-tetrahydro-1,3-benzothiazol-5-yl)methox- y]pyridin-3-yl}sulfonyl)-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-- en-1-yl]methyl piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide; 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin- -1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-N-{[1-(tetrahydro-2H-pyran-4-y- lmethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]sulfonyl}benzamide; 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin- -1-yl)-N-{[3-chloro-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-pyrrolo[2,3-b]py- ridin-5-yl]sulfonyl}-241H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide; 4-(4-{[2-(4-chlorophenyl)-4-(methoxymethyl)-4-methylcyclohex-1-en-1-yl]me- thyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]- phenyl}sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide; N-[(4-{[4,4-bis(hydroxymethyl)cyclohexyl]methoxy}-3-nitrophenyl)sulfonyl]- -4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin- -1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide; N-(2-chloro-4-{[4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]- methyl}piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzoyl]sulfamo- yl}phenyl)-4-methoxypiperidine-1-carboxamide; N-(2-chloro-4-{[4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]- methyl}piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzoyl]sulfamo- yl}phenyl)-4-cyanopiperidine-1-carboxamide; N-(2-chloro-4-{[4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]- methyl}piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzoyl]sulfamo- yl}phenyl)-4-hydroxy-4-methylpiperidine-1-carboxamide; N-(2-chloro-4-{[4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]- methyl}piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzoyl]sulfamo- yl}phenyl)-4-(methoxymethyl)piperidine-1-carboxamide; N-[(5-chloro-6-{[(5r, 8r)-2-oxo-1-oxa-3-azaspiro[4.5]dec-8-yl]methoxy}pyridin-3-yl)sulfonyl]-4-- (4-[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-y- l)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide; N-[(5-chloro-6-{[(5s,8s)-2-oxo-1-oxa-3-azaspiro[4.5]dec-8-yl]methoxy}pyri- din-3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-y- l]methyl}piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide; N-(2-chloro-4-{[4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]- methyl}piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzoyl]sulfamo- yl}phenyl)-4-(morpholin-4-yl)piperidine-1-carboxamide; N-[(5-chloro-6-{[trans-4-hydroxy-4-(methoxymethyl)cyclohexyl]methoxy}pyri- din-3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-y- l]methyl}piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide; N-[(5-chloro-6-{[cis-4-hydroxy-4-(hydroxymethyl)cyclohexyl]methoxy}lpyrid- in-3-yl)sulfonyl]-4-(4-[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]- methyl}piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide; N-[(5-chloro-6-{[trans-4-hydroxy-4-(hydroxymethyl)cyclohexyl]methoxy pyridin-3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-)-e- n-1-yl]methyl}piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamid- e; N-[(5-chloro-6-{[4-fluoro-1-(oxetan-3-yl)piperidin-4-yl]methoxy}pyridin- -3-yl)sulfonyl]-4-(4-{[2-(4-chlorophenyl)-5-methoxy-5-methylcyclohex-1-en-- 1-yl]methyl}piperazin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide; 4-(4-{[2-(4-chlorophenyl)cyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-- nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrr- olo[2,3-b]pyridin-5-yloxy)benzamide; 4-(4-chlorophenyl)-1-methyl-3-[(4-{4-[({3-nitro-4-[(tetrahydro-2H-pyran-4- -ylmethyl)amino]phenyl}sulfonyl)carbamoyl]-3-(1H-pyrrolo[2,3-b]pyridin-5-y- loxy)phenyl}piperazin-1-yl)methyl]cyclohex-3-ene-1-carboxylic acid; and N-[(5-chloro-6-{[1-(oxetan-3-yl)piperidin-4-yl]methoxy}pyridin-3-yl)sulfo- nyl]-4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piper- azin-1-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide.