Reverse hydroxamate-based selective TACE inhibitors.
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.
Kamei
Noriyuki
N
Kaken Pharmaceutical Co., Ltd, 14, Shinomiya, Minamikawara-cho, Kyoto, Yamashina-ku 607-8042, Japan.
Tanaka
Tomohiro
T
Kawai
Kentaro
K
Miyawaki
Kyosei
K
Okuyama
Akihiko
A
Murakami
Yoshiko
Y
Arakawa
Yoshio
Y
Haino
Makoto
M
Harada
Tatsuhiro
T
Shimano
Masanao
M
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
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