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Published on: September 16, 2017
Discovery of selective phosphonamide-based inhibitors of tumor necrosis factor-alpha converting enzyme (TACE)
Masaaki Sawa1, Kiriko Kurokawa, Yoshimasa Inoue
1Department of Chemistry, R&D Laboratories, Nippon Organon K.K., 1-5-90, Tomobuchi-cho, Miyakojima-ku, 16, Osaka 534-00, Japan. masaaki-sawa@dainippon-pharm.co.jp
Abstract:
A novel series of phosphonamide-based inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) was discovered by structural modification of tetrahydroisoquinoline derivative 1b, which was extremely weak inhibitor of TACE. (S)-Isomer at the phosphorus atom (7b) displayed potent inhibition for TACE, while selectivity sparing MMP-1, -3, and -9.
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