SAR of 4-hydroxypiperidine and hydroxyalkyl substituted heterocycles as novel p38 map kinase inhibitors

被引：51

作者：

Revesz, L ^{[1
]}

Di Padova, FE

Buhl, T

Feifel, R

Gram, H

Hiestand, P

Manning, U

Zimmerlin, AG

机构：

[1] Novartis Pharma AG, Arthritis & Bone Res, CH-4002 Basel, Switzerland

[2] Novartis Pharma AG, Preclin Safety, CH-4002 Basel, Switzerland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 11期

关键词：

D O I：

10.1016/S0960-894X(00)00200-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The 4-hydroxypiyeridine substituent was found to confer high p38 selectivity devoid of COX-1 affinity, when attached to a series of pyridinyl substituted heterocycles. Pyridinyloxazole 11 showed a promising in vivo profile with bioavailability of 64% and ED50 in rat collagen induced arthritis of 10 mg/kg po bid. In contrast to pyridinylimidazoles such as SE 203580, 11 did not inhibit human cytochrome P450 isoenzymes. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：1261 / 1264

页数：4

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