Synthesis and biological evaluation of ((4-keto)-phenoxy)methyl biphenyl-4-sulfonamides: A class of potent aggrecanase-1 inhibitors

被引：29

作者：

Hopper, Darrin W. ^{[1
]}

Vera, Matthew D. ^{[1
]}

Howa, David ^{[1
]}

Sabatini, Joshua ^{[1
]}

Xiang, Jason S. ^{[2
]}

Ipek, Manus ^{[2
]}

Thomason, Jennifer ^{[2
]}

Hu, Yonghan ^{[2
]}

Feyfant, Eric ^{[2
]}

Wang, Qin ^{[3
]}

Georgiadis, Katy E. ^{[3
]}

Reifenberg, Erica ^{[3
]}

Sheldon, Richard T. ^{[3
]}

Keohan, Cristin C. ^{[3
]}

Majumdar, Manas K. ^{[3
]}

Morris, Elisabeth A. ^{[3
]}

Skotnicki, Jerauld ^{[1
]}

Sum, Phaik-Eng ^{[1
]}

机构：

[1] Wyeth Res, Dept Chem & Screening Sci, Pearl River, NY 10965 USA

[2] Wyeth Res, Dept Chem & Screening Sci, Cambridge, MA 02140 USA

[3] Wyeth Res, Dept Womens Hlth & Musculoskeletal Biol, Cambridge, MA 02140 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 09期

关键词：

Aggrecanase-1; Agg-1; ADAMTS-4; Biphenylsulfonamides; Osteoarthritis; OA; MMP-2; MMP-13; CARTILAGE DEGRADATION; OSTEOARTHRITIS; PREVENTS; ADAMTS5; MICE;

D O I：

10.1016/j.bmcl.2009.03.056

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

The prevention of aggrecan (a key component of cartilage) cleavage via the inhibition of aggrecanase-1 may provide a unique opportunity to stop the progression of cartilage degradation in osteoarthritis. The evaluation of a series of biphenylsulfonamides resulted in the identification of the ((4-keto)-phenoxy) methyl biphenyl-4-sulfonamides analogs (19-21 and 24) with improved Agg-1 inhibition and MMP-2, MMP-13 activity. (c) 2009 Elsevier Ltd. All rights reserved.

引用

页码：2487 / 2491

页数：5

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