Development of N-4,6-pyrimidine-N-alkyl-N′-phenyl ureas as orally active inhibitors of lymphocyte specific tyrosine kinase

被引：18

作者：

Maier, Jennifer A. ^{[1
]}

Brugel, Todd A. ^{[1
]}

Sabat, Mark ^{[1
]}

Golebiowski, Adam ^{[1
]}

Laufersweiler, Matthew J. ^{[1
]}

VanRens, John C. ^{[1
]}

Hopkins, Corey R. ^{[1
]}

De, Biswanath ^{[1
]}

Hsieh, Lily C. ^{[1
]}

Brown, Kimberly K. ^{[1
]}

Easwaran, Vijayasurian ^{[1
]}

Janusz, Michael J. ^{[1
]}

机构：

[1] Procter & Gamble Pharmaceut, Hlth Care Res Ctr, Mason, OH 45040 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 14期

关键词：

Lck kinase; IL-2; cytokine; rheumatoid arthritis; trisubstituted ureas;

D O I：

10.1016/j.bmcl.2006.04.072

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new class of lymphocyte specific tyrosine kinase (lck) inhibitors based on an N-4,6-pyrimidine-N-alkyl-N'-phenyl urea scaffold is described. Many of these compounds showed low-nanomolar inhibition of lck kinase activity as well as IL-2 synthesis from Jurkat cells. One of these analogs, 7i, was shown to be orally efficacious by in vivo testing in a rat adjuvant-induced arthritis study. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：3646 / 3650

页数：5

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