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 Inhib
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- 作者：Adrian J. Folkes ; Khatereh Ahmadi ; Wendy K. Alderton ; Sonia Alix ; Stewart J. Baker ; Gary Box ; Irina S. Chuckowree ; Paul A. Clarke ; Paul Depledge ; Suzanne A. Eccles ; Lori S. Friedman ; Angela Hayes ; Tim
- 刊名：Journal of Medicinal Chemistry
- 出版年：2008
- 出版时间：September 25, 2008
- 年：2008
- 卷：51
- 期：18
- 页码：5522-5532
- 全文大小：268K
- 年卷期：v.51,no.18(September 25, 2008)
- ISSN：1520-4804
文摘
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 bioavailable inhibitor of PI3K and is currently being evaluated in human clinical trials for the treatment of cancer.