The discovery and optimisation of pyrido[2,3-d]pyrimidine-2,4-diamines as potent and selective inhibitors of mTOR kinase

被引：76

作者：

Malagu, Karine ^{[2
]}

Duggan, Heather ^{[2
]}

Menear, Keith ^{[2
]}

Hummersone, Marc ^{[2
]}

Gomez, Sylvie ^{[2
]}

Bailey, Christine ^{[2
]}

Edwards, Peter ^{[2
]}

Drzewiecki, Jan ^{[2
]}

Leroux, Frederic ^{[2
]}

Quesada, Mar Jimenez ^{[2
]}

Hermann, Gesine ^{[2
]}

Maine, Stephanie ^{[2
]}

Molyneaux, Carrie-Anne ^{[2
]}

Le Gall, Armelle ^{[2
]}

Pullen, James ^{[2
]}

Hickson, Ian ^{[2
]}

Smith, Lisa ^{[2
]}

Maguire, Sharon ^{[2
]}

Martin, Niall ^{[2
]}

Smith, Graeme ^{[1
,2
]}

Pass, Martin ^{[1
]}

机构：

[1] AstraZeneca, Macclesfield SK10 4TG, Cheshire, England

[2] KuDOS Pharmaceut Ltd, Cambridge 3B4 0WG, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 20期

关键词：

Antitumour; mTOR; Serine/threonine kinase; SIGNALING FUNCTIONS; MAMMALIAN PROTEIN; RAPAMYCIN; TARGET; WORTMANNIN; LY294002; PATHWAY; S6K1;

D O I：

10.1016/j.bmcl.2009.08.038

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We describe a novel series of potent inhibitors of the kinase activity of mTOR. The compounds display good selectivity relative to other PI3K-related kinase family members and, in cellular assays, inhibit both mTORC1 and mTORC2 complexes and exhibit good antiproliferative activity. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5950 / 5953

页数：4