Discovery of pyrimidine benzimidazoles as Lck inhibitors: Part I

被引：33

作者：

Zhang, Guobao ^{[1
]}

Ren, Pingda ^{[1
]}

Gray, Nathanael S. ^{[1
]}

Sim, Taebo ^{[1
]}

Liu, Yi ^{[1
]}

Wang, Xia ^{[1
]}

Che, Jianwei ^{[1
]}

Tian, Shin-Shay ^{[1
]}

Sandberg, Mark L. ^{[1
]}

Spalding, Tracy A. ^{[1
]}

Romeo, Russell ^{[1
]}

Iskandar, Maya ^{[1
]}

Chow, Donald ^{[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 | 2008年 / 18卷 / 20期

关键词：

Lck inhibitor; kinase inhibitor; transplantation rejection; autoimmune disease; pyrimidine benzimidazoles;

D O I：

10.1016/j.bmcl.2008.08.104

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 kinase family. Highly efficient parallel syntheses were devised to prepare analogues for SAR studies. A number of these 4-amino-6-benzimidazole-pyrimidines exhibited single-digit nanomolar IC(50)s against Lck in biochemical and cellular assays. These 4-amino-6-benzimidazole-pyrimidines represent a new class of tyrosine kinase inhibitors. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：5618 / 5621

页数：4

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