Pyrimidinylimidazole inhibitors of CSBP/P37 kinase demonstrating decreased inhibition of hepatic cytochrome P450 enzymes

被引：130

作者：

Adams, JL

Boehm, JC

Kassis, S

Gorycki, PD

Webb, EF

Hall, R

Sorenson, M

Lee, JC

Ayrton, A

Griswold, DE

Gallagher, TF

机构：

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

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

[3] SmithKline Beecham Pharmaceut, Dept Drug Metab & Pharmacokinet, King Of Prussia, PA 19406 USA

[4] SmithKline Beecham Pharmaceut, Dept Pulm Pharmacol, King Of Prussia, PA 19406 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1998年 / 8卷 / 22期

关键词：

D O I：

10.1016/S0960-894X(98)00549-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Pyrimidine analogs of the pyridinylimidazole class of CSBP/p38 kinase inhibitors were prepared in an effort to reduce the potent inhibition of hepatic cytochrome P450 observed for the pyridinyl compounds. The substitution of pyrimidin-4-yl, 2-methoxypyrimidin-4-yl, or 2-methylaminopyrimidin-4-yl for pyridin-4-yl effectively dissociates CSBP/p38 kinctse from P450 inhibition for this series and furthermore achieves an increase in oral activity. (C) 1998 Elsevier Science Ltd. All rights reserved.

引用

页码：3111 / 3116

页数：6

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