Reverse hydroxamate-based selective TACE inhibitors

Reverse hydroxamate-based selective TACE inhibitors are described. Compound 18 has a potent TACE inhibitory activity and a high selectivity against MMPs, and has demonstrated an excellent oral inhibitory activity of the lipopolysaccharide (LPS)-stimulated TNF-α production in rats. Reverse hydroxamat...

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry letters Vol. 14; no. 11; pp. 2897 - 2900
Main Authors:	Kamei, Noriyuki, Tanaka, Tomohiro, Kawai, Kentaro, Miyawaki, Kyosei, Okuyama, Akihiko, Murakami, Yoshiko, Arakawa, Yoshio, Haino, Makoto, Harada, Tatsuhiro, Shimano, Masanao
Format:	Journal Article
Language:	English
Published:	Oxford Elsevier Ltd 07-06-2004 Elsevier
Subjects:	ADAM Proteins ADAM17 Protein Administration, Oral Animals Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - pharmacology Hydroxamic Acids - chemical synthesis Hydroxamic Acids - pharmacology Inhibitory Concentration 50 Lipopolysaccharides - pharmacology Medical sciences Metalloendopeptidases - antagonists & inhibitors Pharmacology. Drug treatments Rats Structure-Activity Relationship Tumor Necrosis Factor-alpha - biosynthesis Tumor Necrosis Factor-alpha - drug effects Rat Sulfone Enzyme Rodentia Cytokine Oral administration Hydroxamic acid Enzyme inhibitor Quinoline derivatives Metalloendopeptidases Selectivity In vitro Biological activity Peptidases In vivo Vertebrata Mammalia Animal Piperidine derivatives Hydrolases Benzenic compound Chemical synthesis Tumor necrosis factor α
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Summary:	Reverse hydroxamate-based selective TACE inhibitors are described. Compound 18 has a potent TACE inhibitory activity and a high selectivity against MMPs, and has demonstrated an excellent oral inhibitory activity of the lipopolysaccharide (LPS)-stimulated TNF-α production in rats. 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-α production in rats.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2004.03.048