Discovery of selective phosphonamide-based inhibitors of tumor necrosis factor-alpha converting enzyme (TACE).
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.
Sawa
Masaaki
M
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
Kurokawa
Kiriko
K
Inoue
Yoshimasa
Y
Kondo
Hirosato
H
Yoshino
Kohichiro
K
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
D000577:Amides; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D063065:Organophosphonates; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein