867163-64-2Relevant academic research and scientific papers
Discovery of novel BTK inhibitors with carboxylic acids
Gao, Xiaolei,Wang, James,Liu, Jian,Guiadeen, Deodial,Krikorian, Arto,Boga, Sobhana Babu,Alhassan, Abdul-Basit,Selyutin, Oleg,Yu, Wensheng,Yu, Younong,Anand, Rajan,Liu, Shilan,Yang, Chundao,Wu, Hao,Cai, Jiaqiang,Cooper, Alan,Zhu, Hugh,Maloney, Kevin,Gao, Ying-Duo,Fischmann, Thierry O.,Presland, Jeremy,Mansueto, My,Xu, Zangwei,Leccese, Erica,Zhang-Hoover, Jie,Knemeyer, Ian,Garlisi, Charles G.,Bays, Nathan,Stivers, Peter,Brandish, Philip E.,Hicks, Alexandra,Kim, Ronald,Kozlowski, Joeseph A.
, p. 1471 - 1477 (2017/03/08)
We report the design and synthesis of a series of novel Bruton's Tyrosine Kinase (BTK) inhibitors with a carboxylic acid moiety in the ribose pocket. This series of compounds has demonstrated much improved off-target selectivities including adenosine uptake (AdU) inhibition compared to the piperidine amide series. Optimization of the initial lead compound 4 based on BTK enzyme inhibition, and human peripheral blood mononuclear cell (hPBMC) and human whole blood (hWB) activity led to the discovery of compound 40, with potent BTK inhibition, reduced off target activities, as well as favorable pharmacokinetic profile in both rat and dog.
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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Page/Page column 51, (2010/11/29)
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?).
Fused bicyclic mTOR inhibitors
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Page/Page column 55 - 56, (2008/06/13)
Compounds represented by Formula (I) or a pharmaceutically acceptable salt thereof, are inhibitors of mTOR and useful in the treatment of cancer.
