Structure-based design and synthesis of novel non-zinc chelating MMP-12 inhibitors

被引：61

作者：

Dublanchet, AC

Ducrot, P

Andrianjara, C

O'Gara, M

Morales, R

Compère, D

Denis, A

Blais, S

Cluzeau, P

Courté, K

Hamon, J

Moreau, F

Prunet, ML

Tertre, A

机构：

[1] Pfizer Global Res & Dev, Fresnes Labs, Dept Chem, F-94265 Fresnes, France

[2] Pfizer Global Res & Dev, Fresnes Labs, Dept Res Technol, F-94265 Fresnes, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 16期

关键词：

matrix metalloprotease 12; human metalloelastase; non-zinc chelating inhibitors;

D O I：

10.1016/j.bmcl.2005.05.079

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new class of MMP-12 inhibitors was discovered and optimized using structure-based drug design methods. Modeling studies using a known MMP-12 crystal structure identified a new interaction mode for these new MMP-12 inhibitors. Further optimization resulted in the discovery of a compound displaying nanomolar activity against MMP-12 and which was co-crystallized with MMP-12. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：3787 / 3790

页数：4

共 14 条

[1]

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[2] Matrix metalloproteinase inhibitors 1998 [J].