Structure-based design and synthesis of a series of hydroxamic acids with a quaternary-hydroxy group in P1 as inhibitors of matrix metalloproteinases

被引：30

作者：

Jacobson, IC ^{[1
]}

Reddy, PG

Wasserman, ZR

Hardman, KD

Covington, MB

Arner, EC

Copeland, RA

Decicco, CP

Magolda, RL

机构：

[1] Dupont Merck Pharmaceut Co, Dept Phys & Chem Sci, Wilmington, DE 19880 USA

[2] Dupont Merck Pharmaceut Co, Comp Aided Drug Design, Wilmington, DE 19880 USA

[3] Dupont Merck Pharmaceut Co, Xray Crystallog Dept, Wilmington, DE 19880 USA

[4] Dupont Merck Pharmaceut Co, Inflammatory Dis Res, Expt Stn, Wilmington, DE 19880 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1998年 / 8卷 / 07期

关键词：

D O I：

10.1016/S0960-894X(98)00125-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Examination of the S1 area of the active site of pro-stromelysin has led us to the design of novel and potent inhibitors of matrix metalloproteinases containing constrained quaternary-hydroxy group at pi. The synthesis and biological activity of these compounds with variations at P1', P2', and P3' will be described. (C) 1998 The DuPont Merck Pharmaceutical Company. Published by Elsevier Science Ltd. All rights reserved.

引用

页码：837 / 842

页数：6

共 19 条

[1]

Beckett RP, 1996, EXPERT OPIN THER PAT, V6, P1305

[2] Recent advances in matrix metalloproteinase inhibitor research [J].

Beckett, RP ;

Davidson, AH ;

Drummond, AH ;

Huxley, P ;

Whittaker, M .

DRUG DISCOVERY TODAY, 1996, 1 (01) :16-26

[3] PROTEINASES AND INHIBITORS [J].

CAWSTON, TE .

BRITISH MEDICAL BULLETIN, 1995, 51 (02) :385-401

[4] EVIDENCE FOR METALLOPROTEINASE AND METALLOPROTEINASE INHIBITOR IMBALANCE IN HUMAN OSTEOARTHRITIC CARTILAGE [J].

DEAN, DD ;

MARTELPELLETIER, J ;

PELLETIER, JP ;

HOWELL, DS ;

WOESSNER, JF .

JOURNAL OF CLINICAL INVESTIGATION, 1989, 84 (02) :678-685

[5] X-ray structure of a hydroxamate inhibitor complex of stromelysin catalytic domain and its comparison with members of the zinc metalloproteinase superfamily [J].

Dhanaraj, V ;

Ye, QZ ;

Johnson, LL ;

Hupe, DJ ;

Ortwine, DF ;

Dubar, JB ;

Rubin, JR ;

Pavlovsky, A ;

Humblet, C ;

Blundell, TL .

STRUCTURE, 1996, 4 (04) :375-386

[6]

EMONARD H, 1990, CELL MOL BIOL, V36, P131

[7] Inhibition of matrix metalloproteinases. [J].

Hagmann, WK ;

Lark, MW ;

Becker, JW .

ANNUAL REPORTS IN MEDICINAL CHEMISTRY, VOL 31, 1996, 31 :231-240

[8]

HARDMAN KD, 1997, PROTEIN SOC EUROPEAN

[9] THE ROLE OF STROMELYSIN IN THE CARTILAGE DESTRUCTION THAT ACCOMPANIES INFLAMMATORY ARTHRITIS [J].

HASTY, KA ;

REIFE, RA ;

KANG, AH ;

STUART, JM .

ARTHRITIS AND RHEUMATISM, 1990, 33 (03) :388-397

[10]

HENDERSON B, 1990, Drugs of the Future, V15, P495

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