AMINOPYRIMIDINES USEFUL AS KINASE INHIBITORS

• US 20100310675A1
• Filed: 06/08/2010
• Published: 12/09/2010
• Est. Priority Date: 11/03/2005
• Status: Active Grant

• Current Assignee: Vertex Pharmaceuticals Incorporated
• Original Assignee: Vertex Pharmaceuticals Incorporated
• Inventors: Everitt, Simon, O'Donnell, Michael, Pinder, Joanne, Binch, Hayley, Davis, Chris, Miller, Andrew, Fraysse, Damien, Boyall, Dean, Studley, John, Mortimore, Michael, Rutherford, Alistair, Ramaya, Sharn, Robinson, Daniel
• Granted Patent: US 8,637,511 B2
• Time in Patent Office: Days
• US Class Current: 424/649
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 239/38 One sulfur atom
• 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 403/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 containing three or more hetero rings

Abstract

The present invention relates to compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutically acceptable compositions comprising those compounds and methods of using the compounds and compositions in the treatment of various disease, conditions, and disorders. The invention also provides processes for preparing compounds of the invention.

Claims

1-66. -66. (canceled)

67. A method of inhibiting Aurora protein kinase activity in a biological sample comprising contacting said biological sample with a compound of any one of the following:

68. A method of treating a proliferative disorder in a patient comprising the step of administering to said patient a compound of claim 67.

69. The method according to claim 68, wherein said proliferative disorder is selected from melanoma, myeloma, leukemia, lymphoma, neuroblastoma, or a cancer selected from colon, breast, gastric, ovarian, cervical, lung, central nervous system (CNS), renal, prostate, bladder, pancreatic, brain (gliomas), head and neck, kidney, liver, melanoma, sarcoma, or thyroid cancer in a patient in need thereof wherein said method comprises administering to said patient a compound of claim 67.

70. A method of treating cancer in a subject in need thereof, comprising the sequential or co-administration of a compound of claim 67 or a pharmaceutically acceptable salt thereof, and another therapeutic agent.

71. The method according to claim 70, wherein said therapeutic agent is selected from taxanes, inhibitors of bcr-abl, inhibitors of EGFR, DNA damaging agents, and antimetabolites.

72. The method according to claim 70, wherein said therapeutic agent is selected from Paclitaxel, Gleevec, dasatinib, nilotinib, Tarceva, Iressa, cisplatin, oxaliplatin, carboplatin, anthracyclines, AraC and 5-FU.

73. The method according to claim 70, wherein said therapeutic agent is selected from camptothecin, doxorubicin, idarubicin, Cisplatin, taxol, taxotere, vincristine, tarceva, the MEK inhibitor, U0126, a KSP inhibitor, vorinostat, Gleevec, dasatinib, and nilotinib.

74. A method of inhibiting Aurora protein kinase activity in a biological sample comprising contacting said biological sample with a compound of the following formula:

75. A method of treating a proliferative disorder in a patient comprising the step of administering to said patient a compound of claim 74.

76. The method according to claim 75, wherein said proliferative disorder is selected from melanoma, myeloma, leukemia, lymphoma, neuroblastoma, or a cancer selected from colon, breast, gastric, ovarian, cervical, lung, central nervous system (CNS), renal, prostate, bladder, pancreatic, brain (gliomas), head and neck, kidney, liver, melanoma, sarcoma, or thyroid cancer in a patient in need thereof wherein said method comprises administering to said patient a compound of claim 74.

77. A method of treating cancer in a subject in need thereof, comprising the sequential or co-administration of a compound of claim 74 or a pharmaceutically acceptable salt thereof, and another therapeutic agent.

78. The method according to claim 77, wherein said therapeutic agent is selected from taxanes, inhibitors of bcr-abl, inhibitors of EGFR, DNA damaging agents, and antimetabolites.

79. The method according to claim 77, wherein said therapeutic agent is selected from Paclitaxel, Gleevec, dasatinib, nilotinib, Tarceva, Iressa, cisplatin, oxaliplatin, carboplatin, anthracyclines, AraC and 5-FU.

80. The method according to claim 77, wherein said therapeutic agent is selected from camptothecin, doxorubicin, idarubicin, Cisplatin, taxol, taxotere, vincristine, tarceva, the MEK inhibitor, U0126, a KSP inhibitor, vorinostat, Gleevec, dasatinib, and nilotinib.