THE EFFECT OF N-ACYL SUBSTITUENTS ON THE STABILITY OF MONOCYCLIC BETA-LACTAM INHIBITORS OF HUMAN-LEUKOCYTE ELASTASE

被引：17

作者：

HAGMANN, WK

THOMPSON, KR

SHAH, SK

FINKE, PE

ASHE, BM

WESTON, H

MAYCOCK, AL

DOHERTY, JB

机构：

[1] MERCK RES LABS, DEPT MED CHEM RES, RAHWAY, NJ 07065 USA

[2] MERCK RES LABS, DEPT ENZYMOL, RAHWAY, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1992年 / 2卷 / 07期

关键词：

D O I：

10.1016/S0960-894X(00)80390-X

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Substituted monocyclic beta-lactam have recently been reported as inhibitors of human leukocyte elastase (HLE). Simple N-acetyl-2-azetidinone lead structures were found to undergo N-deacylation as well as beta-lactam ring opening. The development of the N-carbamoyl-2-azetidinone nucleus was crucial to the stability of these compounds for effective oral bioavailability.

引用

页码：681 / 684

页数：4

共 16 条

[11] INHIBITION OF HUMAN-LEUKOCYTE ELASTASE BY C-2 SUBSTITUTED CEPHALOSPORIN SULFONES [J].

HAGMANN, WK ;

OGRADY, LA ;

ASHE, BM ;

DAHLGREN, ME ;

WESTON, H ;

MAYCOCK, AL ;

KNIGHT, WB ;

DOHERTY, JB .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 1989, 24 (06) :599-604

[12]

JANOFF A, 1985, AM REV RESPIR DIS, V132, P417

[13]

MCLEVANEY W, 1990, J CLIN RES, V38, pA485

[14] INHIBITION OF HUMAN-LEUKOCYTE ELASTASE .3. SYNTHESIS AND ACTIVITY OF 3'-SUBSTITUTED CEPHALOSPORINS [J].

SHAH, SK ;

BRAUSE, KA ;

CHANDLER, GO ;

FINKE, PE ;

ASHE, BM ;

WESTON, H ;

KNIGHT, WB ;

MAYCOCK, AL ;

DOHERTY, JB .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (09) :2529-2535

[15]

SHAH SK, 1992, UNPUB

[16]

TRAVIS J, 1988, AM J MED, V84, P37

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