PHOSPHONATES AND PHOSPHINATES - NOVEL LEAVING GROUPS FOR BENZISOTHIAZOLONE INHIBITORS OF HUMAN-LEUKOCYTE ELASTASE

被引：15

作者：

DESAI, RC ^{[1
]}

COURT, JC ^{[1
]}

FERGUSON, E ^{[1
]}

GORDON, RJ ^{[1
]}

HLASTA, DJ ^{[1
]}

DUNLAP, RP ^{[1
]}

FRANKE, CA ^{[1
]}

机构：

[1] STERLING WINTHROP INC, STERLING WINTHROP PHARMACEUT RES DIV, DEPT VASC PHARMACOL, COLLEGEVILLE, PA 19426 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1995年 / 38卷 / 09期

关键词：

D O I：

10.1021/jm00009a017

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel class of alkyl and aryl phosphonate and phosphinate acid-based leaving groups has been developed for utilization in the synthesis of benzoisothiazolone (BIT) inhibitors of human leukocyte elastase (HLE). A number of BITs were synthesized with phosphonate and phosphinate acid-based leaving groups and were found to be potent inhibitors of HLE. Compound 3c with a diethyl phosphonate leaving group is the most potent inhibitor;synthesized in this series with K-i* = 0.035 nM and ED(50) = 2.0 mg/kg.

引用

页码：1571 / 1574

页数：4

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