Development of isoform selective PI3-kinase inhibitors as pharmacological tools for elucidating the PI3K pathway

被引：44

作者：

Bruce, Ian ^{[1
]}

Akhlaq, Mohammed ^{[1
]}

Bloomfield, Graham C. ^{[1
]}

Budd, Emma ^{[1
]}

Cox, Brian ^{[1
]}

Cuenoud, Bernard ^{[1
]}

Finan, Peter ^{[1
]}

Gedeck, Peter ^{[1
]}

Hatto, Julia ^{[1
]}

Hayler, Judy F. ^{[1
]}

Head, Denise ^{[1
]}

Keller, Thomas ^{[1
]}

Kirman, Louise ^{[1
]}

Leblanc, Catherine ^{[1
]}

Le Grand, Darren ^{[1
]}

McCarthy, Clive ^{[1
]}

O'Connor, Desmond ^{[1
]}

Owen, Charles ^{[1
]}

Oza, Mrinalini S. ^{[1
]}

Pilgrim, Gaynor ^{[1
]}

Press, Nicola E. ^{[1
]}

Sviridenko, Lilya ^{[1
]}

Whitehead, Lewis ^{[1
]}

机构：

[1] Novartis Inst Biomed Res, Resp Dis Area, Horsham RH12 5AB, W Sussex, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 17期

关键词：

PI3-Kinase inhibitors; Pharmacological tools; Aminothiazoles; Parallel synthesis; Isoform selectivity; PHOSPHOINOSITIDE; 3-KINASE; P110-ALPHA; KINASES;

D O I：

10.1016/j.bmcl.2012.07.042

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Using a parallel synthesis approach to target a non-conserved region of the PI3K catalytic domain a pan-PI3K inhibitor 1 was elaborated to provide alpha, delta and gamma isoform selective Class I PI3K inhibitors 21, 24, 26 and 27. The compounds had good cellular activity and were selective against protein kinases and other members of the PI3K superfamily including mTOR and DNA-PK. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：5445 / 5450

页数：6

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