Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases

• US 9,174,982 B2
• Filed: 09/26/2013
• Issued: 11/03/2015
• Est. Priority Date: 05/26/2009
• Status: Active Grant

• Current Assignee: Abbvie Incorporated, Genentech, Inc. (Roche Holding AG), The Walter & Eliza Hall Institute Of Medical Research
• Original Assignee: Abbvie Incorporated, Genentech, Inc. (Roche Holding AG), The Walter & Eliza Hall Institute Of Medical Research
• Inventors: Bruncko, Milan, Ding, Hong, Doherty, George A., Elmore, Steven W., Hasvold, Lisa A., Hexamer, Laura, Kunzer, Aaron R., Song, Xiaohong, Souers, Andrew J., Sullivan, Gerard M., Tao, Zhi-Fu, Wang, Gary T., Wang, Le, Wang, Xilu, Wendt, Michael D., Mantei, Robert A., Hansen, Todd M.
• Primary Examiner(s): Jackson, Shawquia
• Application Number:
  US14/038,304
• Publication Number:
  US 20140094471A1
• Time in Patent Office: 768 Days
• Field of Search: 514/252.18, 544/362
• US Class Current: 1/1
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 209/82 Carbazoles; Hydrogenated carbazoles
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 519/00 Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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.

Claims

1. A method of treating a cancer selected from the group consisting of chronic lymphocytic leukemia, lymphoblastic leukemia, follicular lymphoma, a lymphoid malignancy of T cell or B cell origin, myelogenous leukemia, myeloma and breast cancer in a patient, said method comprising administering to the patient a therapeutically effective amount of 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)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide or a pharmaceutically acceptable salt thereof.

2. The method of claim 1, wherein the cancer is chronic lymphocytic leukemia.

3. The method of claim 1, wherein the cancer is lymphoblastic leukemia.

4. A method of treating chronic lymphocytic leukemia in a patient, said method comprising administering to the patient a therapeutically effective amount of a compound 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)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide.

5. A method of treating lymphoblastic leukemia in a patient, said method comprising administering to the patient a therapeutically effective amount of a compound 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)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide.

6. A method of treating myeloma in a patient, said method comprising administering to the patient a therapeutically effective amount of a compound 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)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide.

7. A method of treating breast cancer in a patient, said method comprising administering to the patient a therapeutically effective amount of a compound 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)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide.