Fragment-based discovery of JAK-2 inhibitors

被引：69

作者：

Antonysamy, Stephen ^{[1
]}

Hirst, Gavin ^{[1
]}

Park, Frances ^{[1
]}

Sprengeler, Paul ^{[1
]}

Stappenbeck, Frank ^{[1
]}

Steensma, Ruo ^{[1
]}

Wilson, Mark ^{[1
]}

Wong, Melissa ^{[1
]}

机构：

[1] SGX Pharmaceut Inc, Med Chem, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 01期

关键词：

Fragment-based design; JAK-2; inhibitors; Structure-based design; Aminoindazole; Kinase inhibitors; MYELOPROLIFERATIVE DISORDERS; JAK/STAT PATHWAY; STATS;

D O I：

10.1016/j.bmcl.2008.08.064

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Fragment-based hit identification coupled with crystallographically enabled structure-based drug design was used to design potent inhibitors of JAK-2. After two iterations from fragment 1, we were able to increase potency by greater than 500-fold to provide sulfonamide 13, a 78-nM JAK-2 inhibitor. (C) 2008 Published by Elsevier Ltd.

引用

页码：279 / 282

页数：4

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