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

[1]

BARRETT AJ, 1981, TXB RHEUMATOLOGY, P195

[2] PHARMACOLOGICAL PROFILE OF THE SUBSTITUTED BETA-LACTAM L-659,286 - A MEMBER OF A NEW CLASS OF HUMAN-PMN ELASTASE INHIBITORS [J].

BONNEY, RJ ;

ASHE, B ;

MAYCOCK, A ;

DELLEA, P ;

HAND, K ;

OSINGA, D ;

FLETCHER, D ;

MUMFORD, R ;

DAVIES, P ;

FRANKENFIELD, D ;

NOLAN, T ;

SCHAEFFER, L ;

HAGMANN, W ;

FINKE, P ;

SHAH, S ;

DORN, C ;

DOHERTY, J .

JOURNAL OF CELLULAR BIOCHEMISTRY, 1989, 39 (01) :47-53

[3] DEGRADATION OF HUMAN GLOMERULAR BASEMENT-MEMBRANE WITH PURIFIED LYSOSOMAL PROTEINASES - EVIDENCE FOR PATHOGENIC ROLE OF POLYMORPHONUCLEAR LEUKOCYTE IN GLOMERULONEPHRITIS [J].

DAVIES, M ;

BARRETT, AJ ;

TRAVIS, J ;

SANDERS, E ;

COLES, GA .

CLINICAL SCIENCE AND MOLECULAR MEDICINE, 1978, 54 (03) :233-240

[4]

DAVIES P, 1991, ANN NY ACAD SCI, V624, P219

[5]

DOHERTY JB, 1986, NATURE, V322, P192, DOI 10.1038/322192a0

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

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 .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (09) :2513-2521

[7] INHIBITION OF HUMAN-LEUKOCYTE ELASTASE .2. INHIBITION BY SUBSTITUTED CEPHALOSPORIN ESTERS AND AMIDES [J].

FINKE, PE ;

ASHE, BM ;

KNIGHT, WB ;

MAYCOCK, AL ;

NAVIA, MA ;

SHAH, SK ;

THOMPSON, KR ;

UNDERWOOD, DJ ;

WESTON, H ;

ZIMMERMAN, M ;

DOHERTY, JB .

JOURNAL OF MEDICINAL CHEMISTRY, 1990, 33 (09) :2522-2528

[8]

FIRESTONE RA, 1990, TETRAHEDRON, V46, P2255

[9] A COMPARISON OF ALPHA-1-PROTEINASE INHIBITOR METHOXYSUCCINYL-ALA-ALA-PRO-VAL-CHLOROMETHYLKETONE AND SPECIFIC BETA-LACTAM INHIBITORS IN AN ACUTE MODEL OF HUMAN POLYMORPHONUCLEAR LEUKOCYTE ELASTASE-INDUCED LUNG HEMORRHAGE IN THE HAMSTER [J].

FLETCHER, DS ;

OSINGA, DG ;

HAND, KM ;

DELLEA, PS ;

ASHE, BM ;

MUMFORD, RA ;

DAVIES, P ;

HAGMANN, W ;

FINKE, PE ;

DOHERTY, JB ;

BONNEY, RJ .

AMERICAN REVIEW OF RESPIRATORY DISEASE, 1990, 141 (03) :672-677

[10] PREVENTION OF HUMAN-LEUKOCYTE ELASTASE-MEDIATED LUNG DAMAGE BY 3-ALKYL-4-AZETIDINONES [J].

HAGMANN, WK ;

SHAH, SK ;

DORN, CP ;

OGRADY, LA ;

HALE, JJ ;

FINKE, PE ;

THOMPSON, KR ;

BRAUSE, KA ;

ASHE, BM ;

WESTON, H ;

DAHLGREN, ME ;

MAYCOCK, AL ;

DELLEA, PS ;

HAND, KM ;

OSINGA, DG ;

BONNEY, RJ ;

DAVIES, P ;

FLETCHER, DS ;

DOHERTY, JB .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1991, 1 (10) :545-550

← 1 2 →