Sulfonamide-based hydroxamic acids as potent inhibitors of mouse macrophage metalloelastase

被引：39

作者：

Jeng, AY ^{[1
]}

Chou, M ^{[1
]}

Parker, DT ^{[1
]}

机构：

[1] Novartis Pharmaceut, Metab & Cardiovasc Dis Res, Summit, NJ 07901 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1998年 / 8卷 / 08期

关键词：

D O I：

10.1016/S0960-894X(98)00142-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The structural requirements of sulfonamide-based hydroxamic acid 1 for inhibition of macrophage metalloelastase (MME) were investigated. A short aliphatic group at the R-2 position together with an aromatic group at the R-3 position significantly improved the inhibitory activity. Compounds 32, 34, and 40 were the most potent inhibitors of MME with IC50 values between 5 and 6 nM. (C) 1998 Elsevier Science Ltd. All rights reserved.

引用

页码：897 / 902

页数：6

共 15 条

[1]

ADAMS DO, 1992, INFLAMMATION BASIC P, P63

[2] THIOL AND HYDROXAMIC ACID-CONTAINING INHIBITORS OF ENDOTHELIN-CONVERTING ENZYME [J].

BERTENSHAW, SR ;

TALLEY, JJ ;

ROGERS, RS ;

CARTER, JS ;

MOORE, WM ;

BRANSON, LM ;

KOBOLDT, CM .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1993, 3 (10) :1953-1958

[3] HYDROXAMIC ACIDS AS POTENT INHIBITORS OF ENDOTHELIN-CONVERTING ENZYME FROM HUMAN BRONCHIOLAR SMOOTH-MUSCLE [J].

BIHOVSKY, R ;

LEVINSON, BL ;

LOEWI, RC ;

ERHARDT, PW ;

POLOKOFF, MA .

JOURNAL OF MEDICINAL CHEMISTRY, 1995, 38 (12) :2119-2129

[4]

Furth R., 1992, INFLAMMATION BASIC P, P325

[5] ADVERSE-EFFECTS OF NEUTROPHILS ON THE LUNG [J].

GADEK, JE .

AMERICAN JOURNAL OF MEDICINE, 1992, 92 :S27-S31

[6] INHIBITION OF HUMAN SKIN FIBROBLAST COLLAGENASE, THERMOLYSIN, AND PSEUDOMONAS-AERUGINOSA ELASTASE BY PEPTIDE HYDROXAMIC ACIDS [J].

GROBELNY, D ;

PONCZ, L ;

GALARDY, RE .

BIOCHEMISTRY, 1992, 31 (31) :7152-7154

[7] Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice [J].

Hautamaki, RD ;

Kobayashi, DK ;

Senior, RM ;

Shapiro, SD .

SCIENCE, 1997, 277 (5334) :2002-2004

[8] MOUSE MACROPHAGE METALLOELASTASE EXPRESSED IN BACTERIA ABSOLUTELY REQUIRES ZINC FOR ACTIVITY [J].

JENG, AY ;

WONG, M ;

DUELFER, T ;

SHAPIRO, SD ;

KRAMER, RA ;

HU, SI .

JOURNAL OF BIOCHEMISTRY, 1995, 117 (01) :216-221

[9] Discovery of CGS 27023A, a non-peptidic, potent, and orally active stromelysin inhibitor that blocks cartilage degradation in rabbits [J].

MacPherson, LJ ;

Bayburt, EK ;

Capparelli, MP ;

Carroll, BJ ;

Goldstein, R ;

Justice, MR ;

Zhu, LJ ;

Hu, SI ;

Melton, RA ;

Fryer, L ;

Goldberg, RL ;

Doughty, JR ;

Spirito, S ;

Blancuzzi, V ;

Wilson, D ;

OByrne, EM ;

Ganu, V ;

Parker, DT .

JOURNAL OF MEDICINAL CHEMISTRY, 1997, 40 (16) :2525-2532

[10]

NIEDERMAN MS, 1984, AM REV RESPIR DIS, V129, P943

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