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

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

Bioorganic & medicinal chemistry letters (2009-09-22)
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 Andrews, John A Josey, Takayuki Mimura, Yuichi Shinozaki, Hiromi Yoshiuchi, Takashi Inaba
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 IC50=7.4 nM, the most potent ADAMTS-5 inhibitor reported so far.

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环丙甲酸, 95%