Continued exploration of the triazolopyridine scaffold as a platform for p38 MAP kinase inhibition

被引：23

作者：

Jerome, Kevin D. ^{[1
]}

Rucker, Paul V. ^{[1
]}

Xing, Li ^{[1
]}

Shieh, Huey S. ^{[1
]}

Baldus, John E. ^{[1
]}

Selness, Shaun R. ^{[1
]}

Letavic, Michael A. ^{[2
]}

Braganza, John F. ^{[2
]}

McClure, Kim F. ^{[2
]}

机构：

[1] Pfizer Global Res & Dev, St Louis Labs, Chesterfield, MO 63017 USA

[2] Pfizer Global Res & Dev, Groton Labs, Groton, CT 06340 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 02期

关键词：

p38; Kinase; Triazolopyridines; RHEUMATOID-ARTHRITIS; CROHNS-DISEASE; INFLIXIMAB; REMISSION; EFFICIENT; EFFICACY;

D O I：

10.1016/j.bmcl.2009.11.114

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The structure based drug design, synthesis and structure-activity relationship of a series of C6 sulfur linked triazolopyridine based p38 inhibitors are described. The metabolic deficiencies of this series were overcome through changes in the C6 linker from sulfur to methylene, which was predicted by molecular modeling to be bioisosteric. X-ray of the ethylene linked compound 61 confirmed the predicted binding orientation of the scaffold in the p38 enzyme. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：469 / 473

页数：5

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