title: Reverse hydroxamate-based selective TACE inhibitors.
abstract: Reverse hydroxamate-based selective TACE inhibitors are described. They have potent TACE inhibitory activities and excellent selectivities against MMP-1, 2, 3, 8, 9, 13, 14, and 17. One representative compound, 18 has demonstrated an excellent oral inhibitory activity of the lipopolysaccharide (LPS)-stimulated TNF-alpha production in rats.
authors.affiliation: Kaken Pharmaceutical Co., Ltd, 14, Shinomiya, Minamikawara-cho, Kyoto, Yamashina-ku 607-8042, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kamei
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kawai
authors.forename: Kyosei
authors.initials: K
authors.lastname: Miyawaki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Okuyama
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Murakami
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Arakawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Haino
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Harada
authors.forename: Masanao
authors.initials: M
authors.lastname: Shimano
mesh_terms: D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000284:Administration, Oral; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008070:Lipopolysaccharides / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D051381:Rats; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein; C000606464:Adam17 protein, rat