Coumarin inhibitors of gyrase B with N-propargyloxy-carbamate as an effective pyrrole bioisostere

被引：34

作者：

Periers, AM ^{[1
]}

Laurin, P ^{[1
]}

Ferroud, D ^{[1
]}

Haesslein, JL ^{[1
]}

Klich, M ^{[1
]}

Dupuis-Hamelin, C ^{[1
]}

Mauvais, P ^{[1
]}

Lassaigne, P ^{[1
]}

Bonnefoy, A ^{[1
]}

Musicki, B ^{[1
]}

机构：

[1] Hoechst Marion Roussel, F-93235 Romainville, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 02期

关键词：

D O I：

10.1016/S0960-894X(99)00654-X

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and biological profile in vitro of a series of coumarin inhibitors of gyrase B bearing a N-propargyloxy-carbamate at C-3' of noviose is presented. Replacement of the 5-methylpyrrole-2-carboxylate of coumarin drugs with an N-propargyloxycarbamate bioisostere leads to analogues with improved antibacterial activity. Analysis of crystal structures of coumarin antibiotics with the 24 kDa N-terminal domain of the gyrase B protein provides a rational for the excellent inhibitory potency of C-3' N-alkoxycarbamates. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：161 / 165

页数：5