Kinase array design, back to front: Biaryl amides

被引：21

作者：

Baldwin, Ian ^{[1
]}

Bamborough, Paul ^{[1
]}

Haslam, Claudine G. ^{[1
]}

Hunjan, Suchete S. ^{[1
]}

Longstaff, Tim ^{[1
]}

Mooney, Christopher J. ^{[1
]}

Patel, Shila ^{[1
]}

Quinn, Jo ^{[1
]}

Somers, Don O. ^{[1
]}

机构：

[1] GlaxoSmithKline R&D, Med Res Ctr, Stevenage SG1 2NY, Herts, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 19期

关键词：

kinase array design; p38 MAP kinase; p38a; cFMS; inhibitors; structure-based drug design;

D O I：

10.1016/j.bmcl.2008.08.051

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

New kinase inhibitors can be found by synthesis of targeted arrays of compounds designed using system-based knowledge as well as through screening focused or diverse compounds. Most array strategies aim to add functionality to a fragment that binds in the purine subpocket of the ATP-site. Here, an alternative pharmacophore-guided array approach is described which set out to discover novel purine subpocket-binding groups. Results are shown for p38 alpha and cFMS kinase, for which multiple distinct series with nanomolar potency were discovered. Some of the compounds showed potency in cell-based assays and good pharmacokinetic properties. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：5285 / 5289

页数：5

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