Dipeptidyl nitrile inhibitors of Cathepsin L

被引：45

作者：

Asaad, Nabil ^{[1
]}

Bethel, Paul A. ^{[1
]}

Coulson, Michelle D. ^{[2
]}

Dawson, Jack E. ^{[1
]}

Ford, Susannah J. ^{[1
]}

Gerhardt, Stefan ^{[1
]}

Grist, Matthew ^{[1
]}

Hamlin, Gordon A. ^{[1
]}

James, Michael J. ^{[1
]}

Jones, Emma V. ^{[1
]}

Karoutchi, Galith I. ^{[1
]}

Kenny, Peter W. ^{[1
]}

Morley, Andrew D. ^{[1
]}

Oldham, Keith ^{[1
]}

Rankine, Neil ^{[1
]}

Ryan, David ^{[1
]}

Wells, Stuart L. ^{[1
]}

Wood, Linda ^{[1
]}

Augustin, Martin ^{[3
]}

Krapp, Stephan ^{[3
]}

Simader, Hannes ^{[3
]}

Steinbacher, Stefan ^{[3
]}

机构：

[1] AstraZeneca, Resp & Inflammat Res Area, Macclesfield SK10 4TG, Cheshire, England

[2] AstraZeneca, Safety Assessment, Macclesfield SK10 4TG, Cheshire, England

[3] Proteros Biostruct, D-82152 Martinsried, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 15期

关键词：

Cathepsin; Cathepsin B; Cathepsin K; Cathepsin L; Cathepsin L2; Cathepsin S; Cathepsin V; Cysteine protease; Nitrile; Covalent inhibitor; Selectivity; Protein structure; X-ray crystallography; Structure-based design; Molecular pincer; Conformational lock; Tautomeric lock; Osteoarthritis; Aggrecan; Collagen; Cartilage; PROTEINASES;

D O I：

10.1016/j.bmcl.2009.05.071

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of potent Cathepsin L inhibitors with good selectivity with respect to other cysteine Cathepsins is described and SAR is discussed with reference to the crystal structure of a protein-ligand complex. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：4280 / 4283

页数：4

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