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
收藏
页码：6213 / 6217
页数：5
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