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

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• 作者：Makoto Shiozaki ; Hiroto Imai ; Katsuya Maeda ; Tomoya Miura ; Katsutaka Yasue ; Akira Suma ; Masahiro Yokota ; Yosuke Ogoshi ; Julia Haas ; Andrew M. Fryer ; Ellen R. Laird ; Nicole M. Littmann ; Steven W. Andre
• 关键词：SAR ; ADAMTS-5 (Aggrecanase-2) inhibitors ; 2-Phenyl-1-sulfonylaminocyclopropanecarboxylates
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：1 November 2009
• 年：2009
• 卷：19
• 期：21
• 页码：6213-6217
• 全文大小：725 K

文摘

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 IC₅₀ = 7.4 nM, the most potent ADAMTS-5 inhibitor reported so far.