Synthesis and SAR of 2-phenyl-1-sulfonylaminocyclopropane carboxylates as ADAMTS-5 (Aggrecanase-2) inhibitors

被引：19

作者：

Shiozaki, Makoto ^{[1
]}

Imai, Hiroto ^{[1
]}

Maeda, Katsuya ^{[1
]}

Miura, Tomoya ^{[1
]}

Yasue, Katsutaka ^{[1
]}

Suma, Akira ^{[1
]}

Yokota, Masahiro ^{[1
]}

Ogoshi, Yosuke ^{[1
]}

Haas, Julia ^{[2
]}

Fryer, Andrew M. ^{[2
]}

Laird, Ellen R. ^{[2
]}

Littmann, Nicole M. ^{[2
]}

Andrews, Steven W. ^{[2
]}

Josey, John A. ^{[2
]}

Mimura, Takayuki ^{[1
]}

Shinozaki, Yuichi ^{[1
]}

Yoshiuchi, Hiromi ^{[1
]}

Inaba, Takashi ^{[1
]}

机构：

[1] Japan Tobacco Inc, Cent Pharmaceut Res Inst, Takatsuki Osaka 5691125, Japan

[2] Array BioPharma Inc, Boulder, CO 80301 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 21期

关键词：

SAR; ADAMTS-5 (Aggrecanase-2) inhibitors; 2-Phenyl-1sulfonylaminocyclopropanecarboxylates; LIGAND EFFICIENCY; CYCLOPROPANATION; ESTERS;

D O I：

10.1016/j.bmcl.2009.08.093

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 1-sulfonylaminocyclopropanecarboxylates was synthesized as ADAMTS-5 (Aggrecanase-2) inhibitors. After an intensive investigation of the central cyclopropane core including its absolute stereochemistry and substituents, we found compound 22 with an Agg-2 IC(50) = 7.4 nM, the most potent ADAMTS-5 inhibitor reported so far. (c) 2009 Elsevier Ltd. All rights reserved.

引用

页码：6213 / 6217

页数：5

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