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

被引：668

作者：

Folkes, Adrian J. ^{[1
]}

Ahmadi, Khatereh ^{[1
]}

Alderton, Wendy K. ^{[1
]}

Alix, Sonia ^{[3
]}

Baker, Stewart J. ^{[1
]}

Box, Gary ^{[3
]}

Chuckowree, Irina S. ^{[1
]}

Clarke, Paul A. ^{[3
]}

Depledge, Paul ^{[1
]}

Eccles, Suzanne A. ^{[3
]}

Friedman, Lori S. ^{[2
]}

Hayes, Angela ^{[3
]}

Hancox, Timothy C. ^{[1
]}

Kugendradas, Arumugam ^{[1
]}

Lensun, Letitia ^{[1
]}

Moore, Pauline ^{[1
]}

Olivero, Alan G. ^{[2
]}

Pang, Jodie ^{[2
]}

Patel, Sonal ^{[1
]}

Pergl-Wilson, Giles H. ^{[1
]}

Raynaud, Florence I. ^{[3
]}

Robson, Anthony ^{[1
]}

Saghir, Nahid ^{[1
]}

Salphati, Laurent ^{[2
]}

Sohal, Sukhjit ^{[1
]}

Ultsch, Mark H. ^{[2
]}

Valenti, Melanie ^{[3
]}

Wallweber, Heidi J. A. ^{[2
]}

Wan, Nan Chi ^{[1
]}

Wiesmann, Christian ^{[2
]}

Workman, Paul ^{[3
]}

Zhyvoloup, Alexander ^{[1
]}

Zvelebil, Marketa J. ^{[4
]}

Shuttleworth, Stephen J. ^{[1
]}

机构：

[1] Piramed Pharma, Slough SL1 4NL, Berks, England

[2] Genentech Inc, San Francisco, CA 94080 USA

[3] Canc Res UK, Ctr Canc Therapeut, Inst Canc Res, Haddon Labs, Surrey SN2 5NG, England

[4] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 18期

关键词：

D O I：

10.1021/jm800295d

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

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 pl 110 alpha. 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.

引用

页码：5522 / 5532

页数：11

共 32 条

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