- Discovery of potent, selective and orally bioavailable imidazo[1,5-a] pyrazine derived ACK1 inhibitors
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This Letter describes the medicinal chemistry effort towards a series of novel imidazo[1,5-a]pyrazine derived inhibitors of ACK1. Virtual screening led to the discovery of the initial hit, and subsequent exploration of structure-activity relationships and
- Jin, Meizhong,Wang, Jing,Kleinberg, Andrew,Kadalbajoo, Mridula,Siu, Kam W.,Cooke, Andrew,Bittner, Mark A.,Yao, Yan,Thelemann, April,Ji, Qunsheng,Bhagwat, Shripad,Mulvihill, Kristen M.,Rechka, Josef A.,Pachter, Jonathan A.,Crew, Andrew P.,Epstein, David,Mulvihill, Mark J.
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p. 979 - 984
(2013/03/13)
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- PROCESS FOR THE PREPARATION OF THE COMPOUND OSI - 906
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Process for preparing the tyrosine kinase inhibitor OSI-906 comprises coupling Compound (2) with Compound (6) under specified conditions.
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- Combined treatment with an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors
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The present invention provides a method for treating NSCL, pancreatic, colon or breast cancer tumors or tumor metastases in a patient, comprising administering to the patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein the agent is an mTOR inhibitor, with or without additional agents or treatments, such as other anti-cancer drugs or radiation therapy. The present invention also provides a method for treating tumors or tumor metastases in a patient, comprising administering to said patient simultaneously or sequentially a therapeutically effective amount of a combination of an EGFR kinase inhibitor and an agent that sensitizes tumor cells to the effects of EGFR kinase inhibitors, wherein said agent is an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases. The present invention also provides a pharmaceutical composition comprising an EGFR kinase inhibitor and an mTOR inhibitor that binds to and directly inhibits both mTORC1 and mTORC2 kinases, in a pharmaceutically acceptable carrier. A preferred example of an EGFR kinase inhibitor that can be used in practicing the methods of this invention is the compound erlotinib HCl (also known as TARCEVA?).
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Page/Page column 58-59
(2010/11/29)
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