The Identification of 2-(1H-Indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a Potent, Selective, Orally Bioavailable Inhibitor of Class I PI3 Kinase for the Treatment of Cancer

Autor:	Suzanne A. Eccles, Pauline Moore, Lori Friedman, Paul A. Clarke, Stewart J. Baker, Olivero Alan G, Gary Box, Anthony Robson, Paul Workman, Khatereh Ahmadi, Laurent Salphati, Nahid Saghir, Giles Pergl-Wilson, Irina Chuckowree, Mark H. Ultsch, Wendy K. Alderton, Marketa Zvelebil, Florence I. Raynaud, Sukhjit Sohal, Arumugam Kugendradas, Christian Wiesmann, Adrian Folkes, Sonal Patel, Letitia Lensun, Angela Hayes, Timothy Hancox, Stephen J. Shuttleworth, Alexander Zhyvoloup, Heidi J.A. Wallweber, Paul Depledge, Melanie Valenti, Sonia Alix, Nan Chi Wan, Jodie Pang
Rok vydání:	2008
Předmět:	Indazoles Magnetic Resonance Spectroscopy Pyrimidine Stereochemistry Administration Oral Biological Availability Antineoplastic Agents Pharmacology Chemical synthesis Wortmannin chemistry.chemical_compound Cell Line Tumor Neoplasms Drug Discovery Humans Enzyme Inhibitors PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors Sulfonamides Molecular Structure biology Akt/PKB signaling pathway Kinase Biological activity chemistry Enzyme inhibitor biology.protein Molecular Medicine Drug Screening Assays Antitumor
Zdroj:	Journal of Medicinal Chemistry. 51:5522-5532
ISSN:	1520-4804 0022-2623
DOI:	10.1021/jm800295d
Popis:	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 p110alpha. 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 bioavailable inhibitor of PI3K and is currently being evaluated in human clinical trials for the treatment of cancer.
Databáze:	OpenAIRE
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