Discovery of 4-amino-5,6-biaryl-furo[2,3-d]pyrimidines as inhibitors of Lck:: Development of an expedient and divergent synthetic route and preliminary SAR

被引：43

作者：

DiMauro, Erin F.

Newcomb, John

Nunes, Joseph J.

Bemis, Jean E.

Boucher, Christina

Buchanan, John L.

Buckner, William H.

Cheng, Alan

Faust, Theodore

Hsieh, Faye

Huang, Xin

Lee, Josie H.

Marshall, Teresa L.

Martin, Matthew W.

McGowan, David C.

Schneider, Stephen

Turci, Susan M.

White, Ryan D.

Zhu, Xiaotian

机构：

[1] Amgen Inc, Dept Med Chem, Cambridge, MA 02139 USA

[2] Amgen Inc, Dept HTS & Mol Pharmacol, Cambridge, MA 02139 USA

[3] Amgen Inc, Dept Mol Struct, Cambridge, MA 02139 USA

[4] Amgen Inc, Dept Pharmacokinet & Drug Metab, Newbury Pk, CA 91320 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 08期

关键词：

lymphocyte specific kinase (Lck); anti-inflammatory; kinase inhibitors; furopyrimidine;

D O I：

10.1016/j.bmcl.2007.01.057

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

4-Amino-5,6-biaryl-furo[2,3-d]pyrimidines were identified as potent non-selective inhibitors of Lck. A novel, divergent, and practical synthetic route was developed to access derivatives from bifunctional intermediates. Lead optimization was guided by X-ray crystallographic data, and preliminary SAR led to the identification of compounds with improved cellular potency and selectivity. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：2305 / 2309

页数：5

共 21 条

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