944401-90-5Relevant articles and documents
Structure-Based Drug Design and Synthesis of PI3Kα-Selective Inhibitor (PF-06843195)
Cheng, Hengmiao,Orr, Suvi T. M.,Bailey, Simon,Brooun, Alexei,Chen, Ping,Deal, Judith G.,Deng, Yali L.,Edwards, Martin P.,Gallego, Gary M.,Grodsky, Neil,Huang, Buwen,Jalaie, Mehran,Kaiser, Stephen,Kania, Robert S.,Kephart, Susan E.,Lafontaine, Jennifer,Ornelas, Martha A.,Pairish, Mason,Planken, Simon,Shen, Hong,Sutton, Scott,Zehnder, Luke,Almaden, Chau D.,Bagrodia, Shubha,Falk, Matthew D.,Gukasyan, Hovhannes J.,Ho, Caroline,Kang, Xiaolin,Kosa, Rachel E.,Liu, Ling,Spilker, Mary E.,Timofeevski, Sergei,Visswanathan, Ravi,Wang, Zhenxiong,Meng, Fanxiu,Ren, Shijian,Shao, Li,Xu, Feng,Kath, John C.
, p. 644 - 661 (2021/01/14)
The phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway is a frequently dysregulated pathway in human cancer, and PI3Kα is one of the most frequently mutated kinases in human cancer. A PI3Kα-selective inhibitor may provide the opportunity to spare patients the side effects associated with broader inhibition of the class I PI3K family. Here, we describe our efforts to discover a PI3Kα-selective inhibitor by applying structure-based drug design (SBDD) and computational analysis. A novel series of compounds, exemplified by 2,2-difluoroethyl (3S)-3-{[2′-amino-5-fluoro-2-(morpholin-4-yl)-4,5′-bipyrimidin-6-yl]amino}-3-(hydroxymethyl)pyrrolidine-1-carboxylate (1) (PF-06843195), with high PI3Kα potency and unique PI3K isoform and mTOR selectivity were discovered. We describe here the details of the design and synthesis program that lead to the discovery of 1.
PYRIMIDINE DERIVATIVES AS PI3K INHIBITORS FOR USE IN THE TREATMENT OF CANCER
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, (2016/02/28)
The present inventions relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein ring A, R1, R2a, R2b, R3, R4, R4a, R5- R23, g, j, m, n, x, y, and z are defined herein. The novel pyrimidine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. Additional embodiments relate to pharmaceutical compositions containing the compounds and to methods of using the compounds and compositions in the treatment of abnormal cell growth in mammals.
PYRIMIDINE DERIVATIVES USED AS PI-3 KINASE INHIBITORS
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Page/Page column 121-122, (2010/11/28)
Phosphatidylinositol (PI) 3-kinase inhibitor compounds (I), their pharmaceutically acceptable salts, and prodrugs thereof ; compositions of the new compounds, either alone or in combination with at least one additional therapeutic agent, with a pharmaceutically acceptable carrier; and uses of the new compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of proliferative diseases characterized by the abnormal activity of growth factors, protein serine/threonine kinases, and phospholipid kinases.
