Substituted indazole derivatives active as kinase inhibitors

Abstract

Substituted indazole derivatives of formula (I) and pharmaceutically acceptable salts thereof, as defined in the specification; the compounds of the invention may be useful in therapy in the treatment of diseases associated with a deregulated protein kinase activity, like cancer.

What is claimed is: 
     
         1 . A method for treating a patient having cancer, comprising administering to said patient an effective amount of N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide, or a pharmaceutically acceptable salt thereof, and an effective amount of at least one second therapeutic agent, wherein said at least one second therapeutic agent is selected from antihormonal agents, antiestrogens, antiandrogens, aromatase inhibitors, topoisomerase I inhibitors, topoisomerase II inhibitors, agents that target microtubules, platin-based agents, alkylating agents, DNA damaging agents, DNA intercalating agents, antineoplastic antimetabolites, kinase inhibitors, anti-angiogenic agents, inhibitors of kinesins, therapeutic monoclonal antibodies, mTOR inhibitors, histone deacetylase inhibitors, farnesyl transferase inhibitors, and hypoxic response inhibitors. 
     
     
         2 . The method of  claim 1 , wherein said cancer is selected from breast cancer, lung cancer, non-small cell lung cancer, colorectal cancer, prostate cancer, ovarian cancer, endometrial cancer, gastric cancer, clear cell renal cell carcinoma, uveal melanoma, multiple myeloma, rhabdomyosarcoma, Ewing's sarcoma, Kaposi's sarcoma, medulloblastoma, anaplastic large cell lymphoma, neuroblastoma, rhabdomyosarcoma, glioblastoma, inflammatory myofibroblastic tumor, melanoma, Ewings sarcomas, retinoblastoma, squamous cell carcinoma, seminoma, teratocarcinoma, xeroderma pigmentosum, and thyroid follicular cancer. 
     
     
         3 . The method of  claim 2 , wherein said cancer selected from breast cancer, non-small cell lung cancer, colorectal cancer, prostate cancer, neuroblastoma, melanoma and glioblastoma. 
     
     
         4 . The method of  claim 3 , wherein said cancer is selected from non-small cell lung cancer, colorectal cancer, neuroblastoma, melanoma and glioblastoma. 
     
     
         5 . The method of  claim 4 , wherein said cancer is non-small cell lung cancer. 
     
     
         6 . The method of  claim 4 , wherein said cancer is colorectal cancer. 
     
     
         7 . The method of  claim 4 , wherein said cancer is neuroblastoma. 
     
     
         8 . The method of  claim 4 , wherein said cancer is melanoma. 
     
     
         9 . The method of  claim 4 , wherein said cancer is glioblastoma. 
     
     
         10 . The method of  claim 1 , wherein said N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide, or a pharmaceutically acceptable salt thereof, and said at least one second therapeutic agent are simultaneously administered to said patient. 
     
     
         11 . The method of  claim 1 , wherein said N-[5-(3,5-difluorobenzyl)-1H-indazol-3-yl]-4-(4-methyl-piperazin-1-yl)-2-(tetrahydro-pyran-4-ylamino)-benzamide, or a pharmaceutically acceptable salt thereof, and said at least one second therapeutic agent are sequentially administered to said patient. 
     
     
         12 . The method according to  claim 1 , wherein said at least one second therapeutic agent is selected from kinase inhibitors. 
     
     
         13 . The method according to  claim 12 , wherein said cancer is selected from breast cancer, lung cancer, non-small cell lung cancer, colorectal cancer, prostate cancer, ovarian cancer, endometrial cancer, gastric cancer, clear cell renal cell carcinoma, uveal melanoma, multiple myeloma, rhabdomyosarcoma, Ewing's sarcoma, Kaposi's sarcoma, medulloblastoma, anaplastic large cell lymphoma, neuroblastoma, rhabdomyosarcoma, glioblastoma, inflammatory myofibroblastic tumor, melanoma, Ewings sarcomas, retinoblastoma, squamous cell carcinoma, seminoma, teratocarcinoma, xeroderma pigmentosum, and thyroid follicular cancer. 
     
     
         14 . The method of  claim 13 , wherein said cancer is selected from breast cancer, non-small cell lung cancer, colorectal cancer, prostate cancer, neuroblastoma, melanoma and glioblastoma. 
     
     
         15 . The method of  claim 14 , wherein said cancer is selected from non-small cell lung cancer, colorectal cancer, neuroblastoma, melanoma and glioblastoma. 
     
     
         16 . The method of  claim 15 , wherein said cancer is non-small cell lung cancer. 
     
     
         17 . The method of  claim 15 , wherein said cancer is colorectal cancer. 
     
     
         18 . The method of  claim 15 , wherein said cancer is neuroblastoma. 
     
     
         19 . The method of  claim 15 , wherein said cancer is melanoma. 
     
     
         20 . The method of  claim 15 , wherein said cancer is glioblastoma.