INHIBITION OF HUMAN-LEUKOCYTE ELASTASE .1. INHIBITION BY C-7-SUBSTITUTED CEPHALOSPORIN TERT-BUTYL ESTERS

被引：77

作者：

DOHERTY, JB

ASHE, BM

BARKER, PL

BLACKLOCK, TJ

BUTCHER, JW

CHANDLER, GO

DAHLGREN, ME

DAVIES, P

DORN, CP

FINKE, PE

FIRESTONE, RA

HAGMANN, WK

HALGREN, T

KNIGHT, WB

MAYCOCK, AL

NAVIA, MA

OGRADY, L

PISANO, JM

SHAH, SK

THOMPSON, KR

WESTON, H

ZIMMERMAN, M

机构：

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

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

[3] MERCK SHARP & DOHME LTD,DEPT PROC CHEM RES,RAHWAY,NJ 07065

[4] MERCK SHARP & DOHME LTD,DEPT MOLEC SYST,RAHWAY,NJ 07065

[5] MERCK SHARP & DOHME LTD,DEPT BIOPHYS RES,RAHWAY,NJ 07065

来源：

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

关键词：

D O I：

10.1021/jm00171a028

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Time-dependent inhibitors of the enzyme human leukocyte elastase have been developed based on the cephem nucleus. A series of cephalosporin tert-butyl esters has been examined, and the activity of these compounds has been found to be very sensitive to C-7 substituents, with small, α-oriented, electron-withdrawing groups showing greatest activity. Additionally, the oxidation state of the sulfur atom has been found to play a role in potency, with sulfones showing considerably greater activity than the corresponding sulfides or β-sulfoxides. The a-sulfoxides were inactive. © 1990, American Chemical Society. All rights reserved.

引用

页码：2513 / 2521

页数：9

共 33 条

[1] THE EFFECT OF THE OXIDIZING-AGENTS CHLORAMINE-T AND CIGARETTE-SMOKE ON DOG SERUM PROTEINASE INHIBITOR(S) [J].