The identification of 2-(1 H-Indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno [3, 2-d] pyrimidine (GDC-0941) as a potent, selective, …

AJ Folkes, K Ahmadi, WK Alderton, S Alix…

文献索引：Folkes, Adrian J.; Ahmadi, Khatereh; Alderton, Wendy K.; Alix, Sonia; Baker, Stewart J.; Box, Gary; Chuckowree, Irina S.; Clarke, Paul A.; Depledge, Paul; Eccles, Suzanne A.; Friedman, Lori S.; Hayes, Angela; Hancox, Timothy C.; Kugendradas, Arumugam; Lensun, Letitia; Moore, Pauline; Olivero, Alan G.; Pang, Jodie; Patel, Sonal; Pergl-Wilson, Giles H.; Raynaud, Florence I.; Robson, Anthony; Saghir, Nahid; Salphati, Laurent; Sohal, Sukhjit; Ultsch, Mark H.; Valenti, Melanie; Wallweber, Heidi J. A.; Nan, Chi Wan; Wiesmann, Christian; Workman, Paul; Zhyvoloup, Alexander; Zvelebil, Marketa J.; Shuttleworth, Stephen J. Journal of Medicinal Chemistry, 2008 , vol. 51, # 18 p. 5522 - 5532

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被引用次数: 488

摘要

Phosphatidylinositol-3-kinase (PI3K) is an important target in cancer due to the deregulation of the PI3K/Akt signaling pathway in a wide variety of tumors. A series of thieno [3, 2-d] pyrimidine derivatives were prepared and evaluated as inhibitors of PI3 kinase p110α. The synthesis, biological activity, and further profiling of these compounds are described. This work resulted in the discovery of 17, GDC-0941, which is a potent, selective, orally ...