Pyrimidinylimidazole inhibitors of p38: Cyclic N-1 imidazole substituents enhance p38 kinase inhibition and oral activity

被引：113

作者：

Adams, JL

Boehm, JC

Gallagher, TF

Kassis, S

Webb, EF

Hall, R

Sorenson, M

Garigipati, R

Griswold, DE

Lee, JC

机构：

[1] GlaxoSmithKline Pharmaceut, Dept Med Chem, King Of Prussia, PA 19406 USA

[2] GlaxoSmithKline Pharmaceut, Dept Bone & Cartilage Biol, King Of Prussia, PA 19406 USA

[3] GlaxoSmithKline Pharmaceut, Dept Pulm Pharmacol, King Of Prussia, PA 19406 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 21期

关键词：

D O I：

10.1016/S0960-894X(01)00570-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Optimization of a series of N-1-cycloalkyl-4-aryl-5-(pyrimidin-4-yl)imidazo le inhibitors of p38 kinase is reported. Oral administration of inhibitors possessing a cyclohexan-4-ol or piperidin-4-yl group at N-1 in combination with alkoxy, amino(alkyl), phenoxy and anilino substitution at the 2-position of the pyrimidine was found to potently inhibit LPS-induced TNF in mice and rats. T e selectivity of these new inhibitors for p38 kinase versus eight other protein kinases is high and in all cases exceeds that of SB 203580. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：2867 / 2870

页数：4

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