Synthesis and Matrix Metalloproteinase-12 Inhibitory Activity of Ageladine A Analogs

被引：12

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 Inst, Kanagawa 2521193, Japan

来源：

CHEMICAL & PHARMACEUTICAL BULLETIN | 2011年 / 59卷 / 05期

关键词：

ageladine A; matrix metalloproteinase-12; ageladine A analog; MACROPHAGE METALLOELASTASE MMP-12; MATRIXMETALLOPROTEINASE INHIBITOR; NATURAL-PRODUCT; EXPRESSION; LOCALIZATION; LITHIATION; NAKAMURAI; PYRROLES;

D O I：

10.1248/cpb.59.579

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Synthesis of the 37 ageladine A analogs was accomplished by employing the total synthetic route of natural ageladine A previously explored by us. From the matrix metalloproteinase-12 (MMP-12) inhibitory activity assay carried out using the novel analogs, it appeared evident that the halogen atom at the 2-position of pyrrole ring was essential for the inhibitory activity and that the introduction of a bromine atom into the 4-position of pyrrole ring is very effective for producing potent activity. In addition, exchange of the pyrrole ring to an imidazole ring was extremely effective in increasing activity, and the analog 29 thus obtained was found to show approximately 4 times more potent activity than natural ageladine A.

引用

页码：579 / 596

页数：18

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