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 synthesis and structure-activity relationship of this class are described.
Drug Research Department, Tokyo Research Laboratories, Toa Eiyo Ltd., 2-293-3 Amanuma-cho, Omiya-ku, Saitama-shi, Saitama 330-0834, Japan. hidekazu.masaki@toaeiyo.co.jp
Hidekazu
H
Masaki
Yusuke
Y
Mizuno
Akira
A
Tatui
Akira
A
Murakami
Yuuki
Y
Koide
Shoji
S
Satoh
Atsuo
A
Takahashi
D053818:Chymases; D015195:Drug Design; D006801:Humans; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D013876:Thiophenes / Q000138:chemical synthesis / Q000494:pharmacology
D011480:Protease Inhibitors; D013449:Sulfonamides; D013876:Thiophenes; C088015:benzothiophene; D012697:Serine Endopeptidases; D053818:Chymases