Heterocycle-based MMP inhibitors with P2′ substituents

被引：41

作者：

Pikul, S ^{[1
]}

Dunham, KM ^{[1
]}

Almstead, NG ^{[1
]}

De, B ^{[1
]}

Natchus, MG ^{[1
]}

Taiwo, YO ^{[1
]}

Williams, LE ^{[1
]}

Hynd, BA ^{[1
]}

Hsieh, LC ^{[1
]}

Janusz, MJ ^{[1
]}

Gu, F ^{[1
]}

Mieling, GE ^{[1
]}

机构：

[1] Procter & Gamble Pharmaceut, Hlth Care Res Ctr, Mason, OH 45040 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 08期

关键词：

D O I：

10.1016/S0960-894X(01)00137-8

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Potent and selective inhibition of matrix metalloproteinases was demonstrated fur a series of sulfonamide-based hydroxamic acids. The design of the heterocyclic sulfonamides incorporates a six- or seven-member central ring with a P2 ' substituent that can be modified. Binding interactions of this substituent at the S2 ' site are believed to contribute to high inhibitory potency against stromelysin, collagenase-3 and gelatinases A and B, and to provide selectivity against collagenase-1 and matrilysin. An X-ray structure of a stromelysin-inhibitor complex was obtained to provide insights into the SAR and selectivity trends observed for the series. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：1009 / 1013

页数：5

共 14 条

[1] Design, synthesis, and biological evaluation of potent thiazine- and thiazepine-based matrix metalloproteinase inhibitors [J].

Almstead, NG ;

Bradley, RS ;

Pikul, S ;

De, B ;

Natchus, MG ;

Taiwo, YO ;

Gu, F ;

Williams, LE ;

Hynd, BA ;

Janusz, MJ ;

Dunaway, CM ;

Mieling, GE .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (22) :4547-4562

[2] Molecular recognition of protein-ligand complexes: Applications to drug design [J].

Babine, RE ;

Bender, SL .

CHEMICAL REVIEWS, 1997, 97 (05) :1359-1472

[3]

BARRACLOUGH P, 1991, J CHEM RES-S, P306

[4]

Bender S. L., 1998, Patent, Patent No. [5753653, US5753653A]

[5] GENE-EXPRESSION (COLLAGENASE, TISSUE INHIBITOR OF METALLOPROTEINASES, COMPLEMENT, AND HLA DR) IN RHEUMATOID-ARTHRITIS AND OSTEOARTHRITIS SYNOVIUM - QUANTITATIVE-ANALYSIS AND EFFECT OF INTRAARTICULAR CORTICOSTEROIDS [J].

FIRESTEIN, GS ;

PAINE, MM ;

LITTMAN, BH .

ARTHRITIS AND RHEUMATISM, 1991, 34 (09) :1094-1105

[6]

GREENWALD RA, 1999, ANN NY ACAD SCI, P87

[7] The synthesis and biological activity of a novel series of diazepine MMP inhibitors [J].

Levin, JI ;

DiJoseph, JF ;

Killar, LM ;

Sung, A ;

Walter, T ;

Sharr, MA ;

Roth, CE ;

Skotnicki, JS ;

Albright, JD .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (19) :2657-2662

[8] DEMONSTRATION OF TISSUE COLLAGENASE ACTIVITY INVIVO AND ITS RELATIONSHIP TO INFLAMMATION SEVERITY IN HUMAN GINGIVA [J].

OVERALL, CM ;

WIEBKIN, OW ;

THONARD, JC .

JOURNAL OF PERIODONTAL RESEARCH, 1987, 22 (02) :81-88

[9] Design and synthesis of phosphinamide-based hydroxamic acids as inhibitors of matrix metalloproteinases [J].

Pikul, S ;

Dunham, KLM ;

Almstead, NG ;

De, B ;

Natchus, MG ;

Anastasio, MV ;

McPhail, SJ ;

Snider, CE ;

Taiwo, YO ;

Chen, LY ;

Dunaway, CM ;

Gu, F ;

Mieling, GE .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (01) :87-94

[10] Discovery of potent, achiral matrix metalloproteinase inhibitors [J].

Pikul, S ;

Dunham, KLM ;

Almstead, NG ;

De, B ;

Natchus, MG ;

Anastasio, MV ;

McPhail, SJ ;

Snider, CE ;

Taiwo, YO ;

Rydel, T ;

Dunaway, CM ;

Gu, F ;

Mieling, GE .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (19) :3568-3571

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