title: Discovery of selective phosphonamide-based inhibitors of tumor necrosis factor-alpha converting enzyme (TACE).
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.
authors.affiliation: Department 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
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sawa
authors.forename: Kiriko
authors.initials: K
authors.lastname: Kurokawa
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Inoue
authors.forename: Hirosato
authors.initials: H
authors.lastname: Kondo
authors.forename: Kohichiro
authors.initials: K
authors.lastname: Yoshino
mesh_terms: D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D007536:Isomerism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D063065:Organophosphonates / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D063065:Organophosphonates; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein