A novel series of p38 MAP kinase inhibitors for the potential treatment of rheumatoid arthritis

被引:25
作者
Brown, DS [1 ]
Belfield, AJ [1 ]
Brown, GR [1 ]
Campbell, D [1 ]
Foubister, A [1 ]
Masters, DJ [1 ]
Pike, KG [1 ]
Snelson, WL [1 ]
Wells, SL [1 ]
机构
[1] AstraZeneca, Macclesfield SK10 4TG, Cheshire, England
关键词
p38 MAP kinase inhibitors;
D O I
10.1016/j.bmcl.2004.08.006
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A novel p38 MAP kinase inhibitor structural class was discovered through selectivity screening. The rational analogue design, synthesis and structure-activity relationship of this series of bisamide inhibitors is reported. The inhibition in vitro of human p38alpha enzyme activity and lipopolysaccharide-induced tumour necrosis factor-alpha release is described for the series. The activity in vivo and pharmacokinetic properties are exemplified for the more potent analogues. (C) 2004 Elsevier Ltd. All rights reserved.
引用
收藏
页码:5383 / 5387
页数:5
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