Structure–Activity relationship of benzo[ b]thiophene-2-sulfonamide derivatives as novel human chymase inhibitors

We have identified a new class of chymase inhibitor through a substituent analysis of MWP00965, which we previously discovered by in silico screening. TY-51076 ( 7) showed high potency (IC 50=56 nM) and excellent selectivity for chymase compared to chymotrypsin and cathepsin G (>400-fold). The sy...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2003-11, Vol.13 (22), p.4085-4088
Hauptverfasser:	Masaki, Hidekazu, Mizuno, Yusuke, Tatui, Akira, Murakami, Akira, Koide, Yuuki, Satoh, Shoji, Takahashi, Atsuo
Format:	Artikel
Sprache:	eng
Schlagworte:	Analytical, structural and metabolic biochemistry Biological and medical sciences Chymases Drug Design Enzymes and enzyme inhibitors Fundamental and applied biological sciences. Psychology Humans Hydrolases Medical sciences Miscellaneous Pharmacology. Drug treatments Protease Inhibitors - chemical synthesis Protease Inhibitors - pharmacology Serine Endopeptidases - drug effects Serine Endopeptidases - metabolism Structure-Activity Relationship Sulfonamides - chemical synthesis Sulfonamides - pharmacology Thiophenes - chemical synthesis Thiophenes - pharmacology
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Zusammenfassung:	We have identified a new class of chymase inhibitor through a substituent analysis of MWP00965, which we previously discovered by in silico screening. TY-51076 ( 7) showed high potency (IC 50=56 nM) and excellent selectivity for chymase compared to chymotrypsin and cathepsin G (>400-fold). The synthesis and structure–activity relationship of this class are described. TY-51076 ( 7) showed high potency (IC 50=56 nM) and excellent selectivity for chymase compared to chymotrypsin and cathepsin G (>400-fold). The synthesis and structure–activity relationship of this class are described.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2003.08.040