SAR of benzoylpyridines and benzophenones as p38α MAP kinase inhibitors with oral activity

被引：38

作者：

Revesz, L ^{[1
]}

Blum, E ^{[1
]}

Di Padova, FE ^{[1
]}

Buhl, T ^{[1
]}

Feifel, R ^{[1
]}

Gram, H ^{[1
]}

Hiestand, P ^{[1
]}

Manning, U ^{[1
]}

Rucklin, G ^{[1
]}

机构：

[1] Novartis Inst Biomed Res Arthrit & Bone Metab, CH-4002 Basel, Switzerland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 13期

关键词：

D O I：

10.1016/j.bmcl.2004.03.111

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Benzoylpyridines and benzophenones were synthesized and evaluated in vitro as p38alpha inhibitors and in vivo in several models of rheumatoid arthritis. Oral activity was found to depend upon substitution: 1,1-dimethylpropynylamine substituted benzophenone 10b (IC50: 14 nM) and pyridinoyl substituted benzimidazole 17b (IC50: 21 nM) showed highest efficacy and selectivity with ED50S of 9.5 and 8.6 mg/kg po in CIA. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：3601 / 3605

页数：5

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