Critical modifications of the ISO-1 scaffold improve its potent inhibition of macrophage migration inhibitory factor (MIF) tautomerase activity

被引：48

作者：

Cheng, Kai Fan

Al-Abed, Yousef

机构：

[1] N Shore LIJ Hlth Syst, Dept Med Chem, Feinstein Inst Med Res, Manhasset, NY 11030 USA

[2] NYU, Sch Med, New York, NY USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 13期

关键词：

MIF; ISO-1; tautomerase activity; enzyme;

D O I：

10.1016/j.bmcl.2006.04.038

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Based on the scaffold of (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), an inhibitor of the proinflammatory cytokine MIF, two critical modifications and chiral resolution have significantly improved the potency of the inhibition. Compound (R)-17 is 20-fold more potent than ISO-1 and inhibits MIF tautomerase activity with an IC50 of 550 nM. (c) 2006 Elsevier Ltd. All rights reserved.

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收藏

页码：3376 / 3379

页数：4

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