Structure-activity relationships of the peptide deformylase inhibitor BB-3497:: Modification of the methylene spacer and the P1′ side chain

被引：32

作者：

Davies, SJ ^{[1
]}

Ayscough, AP ^{[1
]}

Beckett, RP ^{[1
]}

Bragg, RA ^{[1
]}

Clements, JM ^{[1
]}

Doel, S ^{[1
]}

Grew, C ^{[1
]}

Launchbury, SB ^{[1
]}

Perkins, GM ^{[1
]}

Pratt, LM ^{[1
]}

Smith, HK ^{[1
]}

Spavold, ZM ^{[1
]}

Thomas, SW ^{[1
]}

Todd, RS ^{[1
]}

Whittaker, M ^{[1
]}

机构：

[1] British Biotech Pharmaceut Ltd, Oxford OX4 6LY, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 16期

关键词：

D O I：

10.1016/S0960-894X(03)00532-8

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Structural modifications to the peptide deformylase inhibitor BB-3497 are described. In this paper, we describe the initial SAR around this lead for modifications to the methylene spacer and the P1' side chain. Enzyme inhibition and antibacterial activity data revealed that the optimum distance between the N-formyl hydroxylamine metal binding group and the P1' side chain is one unsubstituted methylene unit. Additionally, lipophilic P1' side chains that closely mimic the methionine residue in the substrate provided compounds with the best microbiological profile. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：2709 / 2713

页数：5

共 18 条

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