Reverse hydroxamate-based selective TACE inhibitors

Noriyuki Kamei; Tomohiro Tanaka; Kentaro Kawai; Kyosei Miyawaki; Akihiko Okuyama; Yoshiko Murakami; Yoshio Arakawa; Makoto Haino; Tatsuhiro Harada; Masanao Shimano

doi:10.1016/j.bmcl.2004.03.048

Reverse hydroxamate-based selective TACE inhibitors

Bioorg Med Chem Lett. 2004 Jun 7;14(11):2897-900. doi: 10.1016/j.bmcl.2004.03.048.

Authors

Noriyuki Kamei¹, Tomohiro Tanaka, Kentaro Kawai, Kyosei Miyawaki, Akihiko Okuyama, Yoshiko Murakami, Yoshio Arakawa, Makoto Haino, Tatsuhiro Harada, Masanao Shimano

Affiliation

¹ Kaken Pharmaceutical Co., Ltd, 14, Shinomiya, Minamikawara-cho, Kyoto, Yamashina-ku 607-8042, Japan.

PMID: 15125955
DOI: 10.1016/j.bmcl.2004.03.048

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.

MeSH terms

ADAM Proteins
ADAM17 Protein
Administration, Oral
Animals
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / pharmacology
Hydroxamic Acids / chemical synthesis
Hydroxamic Acids / pharmacology*
Inhibitory Concentration 50
Lipopolysaccharides / pharmacology
Metalloendopeptidases / antagonists & inhibitors*
Rats
Structure-Activity Relationship
Tumor Necrosis Factor-alpha / biosynthesis
Tumor Necrosis Factor-alpha / drug effects

Substances

Enzyme Inhibitors
Hydroxamic Acids
Lipopolysaccharides
Tumor Necrosis Factor-alpha
ADAM Proteins
Metalloendopeptidases
ADAM17 Protein
Adam17 protein, rat