INHIBITION OF HUMAN-LEUKOCYTE ELASTASE .3. SYNTHESIS AND ACTIVITY OF 3'-SUBSTITUTED CEPHALOSPORINS

被引：54

作者：

SHAH, SK

BRAUSE, KA

CHANDLER, GO

FINKE, PE

ASHE, BM

WESTON, H

KNIGHT, WB

MAYCOCK, AL

DOHERTY, JB

机构：

[1] MERCK SHARP & DOHME LTD,DEPT BIOCHEM INFLAMMAT RES,RAHWAY,NJ 07065

[2] MERCK SHARP & DOHME LTD,DEPT ENZYMOL,RAHWAY,NJ 07065

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1990年 / 33卷 / 09期

关键词：

D O I：

10.1021/jm00171a030

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Several 3’-substituted cephalosporin sulfones were synthesized from 3-(hydroxymethyl)cephalosporin, which was prepared by Ti(OiPr)4 hydrolysis of the corresponding acetate. A method was also developed to prepare a 3-vinylcephalosporin. Some of these compounds were found to be potent time-dependent inhibitors of human leukocyte elastase (HLE). The HLE inhibitory activity was correlated with σI and it was concluded that the potency was determined by the electron-withdrawing ability as well as the size of the substituent. A mechanism for inhibition of HLE by cephalosporin sulfones is proposed. © 1990, American Chemical Society. All rights reserved.

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页码：2529 / 2535

页数：7

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