Mycophenolic acid analogs with a modified metabolic profile

被引：10

作者：

Chen, Liqiang ^{[1
]}

Wilson, Daniel J. ^{[1
]}

Labello, Nicholas P. ^{[1
]}

Jayaram, Hiremagalur N. ^{[2
,3
]}

Pankiewicz, Krzysztof W. ^{[1
]}

机构：

[1] Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, Minneapolis, MN 55455 USA

[2] Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA

[3] Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 20期

关键词：

mycophenolic acid; inosine monophosphate dehydrogenase; allylic substitution;

D O I：

10.1016/j.bmc.2008.08.062

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mycophenolic acid (MPA), a clinically used immunosuppressant, is extensively metabolized into an inactive C7-glucuronide and removed from circulation. To circumvent the metabolic liability imposed by the C7-hydroxyl group, we have designed a series of hybrid MPA analogs based on the pharmacophores present in MPA and new generations of inosine monophosphate dehydrogenase (IMPDH) inhibitors. The synthesis of MPA analogs has been accomplished by an allylic substitution of a common lactone. Biological evaluations of these analogs and a preliminary structure-activity relationship (SAR) are presented. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：9340 / 9345

页数：6

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