The synthesis of novel matrix metalloproteinase inhibitors employing the Ireland-Claisen rearrangement

被引：18

作者：

Pratt, LM ^{[1
]}

Beckett, RP ^{[1
]}

Bellamy, CL ^{[1
]}

Corkill, DJ ^{[1
]}

Cossins, J ^{[1
]}

Courtney, PF ^{[1
]}

Davies, SJ ^{[1
]}

Davidson, AH ^{[1
]}

Drummond, AH ^{[1
]}

Helfrich, K ^{[1
]}

Lewis, CN ^{[1
]}

Mangan, M ^{[1
]}

Martin, FM ^{[1
]}

Miller, K ^{[1
]}

Nayee, P ^{[1
]}

Ricketts, ML ^{[1
]}

Thomas, W ^{[1
]}

Todd, RS ^{[1
]}

Whittaker, M ^{[1
]}

机构：

[1] British Biotech Pharmaceut Ltd, Oxford OX4 5LY, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1998年 / 8卷 / 11期

关键词：

D O I：

10.1016/S0960-894X(98)00218-2

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Matrix metalloproteinase inhibitors of general formula (1) were synthesised by a route involving an Ireland-Claisen rearrangement which enables systematic modification of the substituent alpha to the hydroxamic acid. An analogue (12c) possessing an alpha-cyclopentyl group is a potent broad spectrum inhibitor that displays high and sustained blood levels following oral dosing in both the rat and marmoset ex-vivo bioassays. This compound and analogues are also potent inhibitors of TNF alpha release. (C) 1998 Elsevier Science Ltd. All rights reserved.

引用

页码：1359 / 1364

页数：6

共 16 条

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