Pyrazoloheteroaryls:: Novel p38α MAP kinase inhibiting scaffolds with oral activity

被引：79

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
]}

Neumann, U ^{[1
]}

Rucklin, G ^{[1
]}

机构：

[1] Novartis Inst Biomed Res, Global Discovery Chem, CH-4002 Basel, Switzerland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 02期

关键词：

p38; inhibition; MAP kinase inhibition; rheumatoid arthriitis; antiarthritic; anti-inflammatory; collagen-induced arthritis; adjuvant-induced arthritis;

D O I：

10.1016/j.bmcl.2005.10.015

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A test library with three novel p38 alpha inhibitory scaffolds and a narrow set of substituents was prepared. Appropriate combination of substituent and scaffold generated potent p38 alpha inhibitors, for example, pyrazolo[3,4-b]pyridine 9, pyrazolo[3,4-d]pyrimidine 18a and pyrazolo[3,4-b]pyrazine 23b with potent in vivo activity upon oral administration in animal models of rheumatoid arthritis. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：262 / 266

页数：5

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