Highly Potent, Orally Available Anti-inflammatory Broad-Spectrum Chemokine Inhibitors

被引：33

作者：

Fox, David J. ^{[2
]}

Reckless, Jill ^{[1
]}

Lingard, Hannah ^{[2
]}

Warren, Stuart ^{[2
]}

Grainger, David J. ^{[1
]}

机构：

[1] Univ Cambridge, Dept Med, Addenbrookes Hosp, Cambridge CB2 2QQ, England

[2] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 11期

基金：

英国工程与自然科学研究理事会;

关键词：

IN-VIVO; RECEPTOR STRUCTURE; ANTAGONISTS; NR58-3.14.3; DISCOVERY;

D O I：

10.1021/jm900133w

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 3-acylaminocaprolactams are inhibitors of chemokine-induced chemotaxis. Branching of the side chain alpha-carbon provides highly potent inhibitors of a range of CC and CXC chemokines. The most potent compound has an ED50 of 40 pM. Selected compounds were tested in an in vivo inflammatory assay, and the best compound reduces TNF-alpha levels with an ED50 of 0.1 mu g/kg when administered by either subcutaneous injection or oral delivery.

引用

页码：3591 / 3595

页数：5

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