Synthesis of potent inhibitors of histidinol dehydrogenase

被引：16

作者：

Dancer, JE

Ford, MJ

Hamilton, K

Kilkelly, M

Lindell, SD

OMahony, MJ

SavilleStones, EA

机构：

[1] AGREVO UK LTD, HAUXTON CB2 5HU, CAMBS, ENGLAND

[2] AGREVO UK LTD, SAFFRON WALDEN CB10 1XL, ESSEX, ENGLAND

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1996年 / 6卷 / 17期

关键词：

D O I：

10.1016/0960-894X(96)00384-8

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel inhibitors of histidinol dehydrogenase are described. The most potent inhibitors, compounds 18 (K-i* = 4.4 nM) and 19 (K-i* = 2.9 nM) exploit a hitherto unreported lipophilic binding pocket adjoining the active site. Preliminary SAR data for this pocket are detailed. The electrophilic ketone 6 designed to bind to an active site nucleophile was a considerably weaker inhibitor (IC50 similar to 20 mu M). Copyright (C) 1996 Elsevier Science Ltd

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页码：2131 / 2136

页数：6

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