Synthesis and biological evaluation of hydroxamate-based inhibitors of glutamate carboxypeptidase II

被引：44

作者：

Stoermer, D ^{[1
]}

Liu, Q ^{[1
]}

Hall, MR ^{[1
]}

Flanary, JM ^{[1
]}

Thomas, AG ^{[1
]}

Rojas, C ^{[1
]}

Slusher, BS ^{[1
]}

Tsukamoto, T ^{[1
]}

机构：

[1] Guilford Pharmaceut Inc, Baltimore, MD 21224 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 13期

关键词：

D O I：

10.1016/S0960-894X(03)00407-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of hydroxamic acids has been prepared as potential inhibitors of glutamate carboxypeptidase II (GCP II). Compounds based on a Pl' residue (primed-side inhibitors) were more potent than those based on a Pl group (unprimed-side inhibitors). Inhibitory potency of the primed-side GCP II inhibitors was found to be dependent on the number of methylene units between the hydroxamate group and pentanedioic acid. Succinyl hydroxamic acid derivative, 2-(hydroxycarbamoylmethyl)pentanedioic acid, is the most potent GCP II inhibitor with an IC50 value of 220 nM The comparison of the results to those of other classes of GCP II inhibitors as well as hydroxamate-based MNIP inhibitors provides further insight into the structure-activity relationships of GCP II inhibition. (C) 2003 Elsevier Science Ltd. All rights reserved.

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页码：2097 / 2100

页数：4

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