Discovery of pyrimidine benzimidazoles as Src-family selective Lck inhibitors. Part II

被引：7

作者：

Zhang, Guobao ^{[1
]}

Ren, Pingda ^{[1
]}

Gray, Nathanael S. ^{[1
]}

Sim, Taebo ^{[1
]}

Wang, Xia ^{[1
]}

Liu, Yi ^{[1
]}

Che, Jianwei ^{[1
]}

Dong, Weitong ^{[1
]}

Tian, Shin-Shay ^{[1
]}

Sandberg, Mark L. ^{[1
]}

Spalding, Tracy A. ^{[1
]}

Romeo, Russell ^{[1
]}

Iskandar, Maya ^{[1
]}

Wang, Zhiliang ^{[1
]}

Seidel, H. Martin ^{[1
]}

Karanewsky, Donald S. ^{[1
]}

He, Yun ^{[1
]}

机构：

[1] Novartis Res Fdn GNF, Genom Inst, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 23期

关键词：

Lck inhibitor; Kinase inhibitor; Transplantation rejection; Autoimmune disease; Pyrimidine benzimidazoles; PROTEIN-TYROSINE KINASE; SIGNAL-TRANSDUCTION; P56(LCK); RECEPTOR; DESIGN;

D O I：

10.1016/j.bmcl.2009.09.123

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 4-amino-6-benzimidazole-pyrimidines was designed to target lymphocyte-specific tyrosine kinase (Lck), a member of the Src-family kinases (SFKs). These type II inhibitors were optimized using a cellular Lck-dependent proliferation assay and are capable of inhibiting Lck at single-digit nanomolar concentrations. This scaffold is likely to serve a valuable template for developing potent inhibitors of a number of SFKs. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：6691 / 6695

页数：5

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