A BENZISOTHIAZOLONE CLASS OF POTENT, SELECTIVE MECHANISM-BASED INHIBITORS OF HUMAN-LEUKOCYTE ELASTASE

被引：43

作者：

HLASTA, DJ ^{[1
]}

BELL, MR ^{[1
]}

BOAZ, NW ^{[1
]}

COURT, JJ ^{[1
]}

DESAI, RC ^{[1
]}

FRANKE, CA ^{[1
]}

MURA, AJ ^{[1
]}

SUBRAMANYAM, C ^{[1
]}

DUNLAP, RP ^{[1
]}

机构：

[1] EASTMAN KODAK CO,RES LABS,ROCHESTER,NY 14650

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1994年 / 4卷 / 15期

关键词：

D O I：

10.1016/S0960-894X(01)80374-7

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new type of mechanism-based inhibitor of human leukocyte elastase (HLE) is described that are designed to inhibit HLE by a suicide route to form an inhibitor-enzyme complex by cross linking the enzyme active site. A mechanism of HLE inhibition is proposed and was used to design analogues with improved potency. The structure-activity relationships described in this paper are consistent with the proposed mechanism of HLE inhibition, and led to WIN 62785 (12), the most potent compound in this series with a K-i* = 0.3 nM.

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页码：1801 / 1806

页数：6

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