Synthesis of novel ageladine A analogs showing more potent matrix metalloproteinase (MMP)-12 inhibitory activity than the natural product

被引：23

作者：

Ando, Naoki ^{[1
]}

Terashima, Shiro ^{[2
]}

机构：

[1] Kyorin Pharmaceut Co Ltd, Discovery Res Labs, Nogi, Tochigi 3290114, Japan

[2] Sagami Chem Res Ctr, Kanagawa 2521193, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 18期

关键词：

Ageladine A; Matrix metalloproteinase (MMP)-12; MACROPHAGE METALLOELASTASE MMP-12; EXPRESSION; PYRROLE-2-CARBOXALDEHYDES; LOCALIZATION; LITHIATION; PYRROLES; DIMER;

D O I：

10.1016/j.bmcl.2009.07.099

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

By employing a previously established synthetic scheme, the synthesis described in the title was carried out in order to explore the substituent effects in the pyrrole ring of ageladine A on MMP-12 inhibitory activity. It became evident that a halogen atom (Br or Cl) at the 2-position and an additional bromine atom at the 4-position are highly effective for improving the inhibitory activity. These studies led us to discover three novel ageladine A analogs (4a. c, o) showing more potent MMP-12 inhibitory activity than the natural product. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5461 / 5463

页数：3

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