75785-11-4Relevant articles and documents
Discovery, optimization, and biological evaluation of 5-(2- (trifluoromethyl)phenyl)indazoles as a novel class of transient receptor potential A1 (TRPA1) antagonists
Rooney, Lisa,Vidal, Agnès,D'Souza, Anne-Marie,Devereux, Nick,Masick, Brian,Boissel, Valerie,West, Ryan,Head, Victoria,Stringer, Rowan,Lao, Jianmin,Petrus, Matt J.,Patapoutian, Ardem,Nash, Mark,Stoakley, Natalie,Panesar, Moh,Verkuyl, J. Martin,Schumacher, Andrew M.,Petrassi, H. Michael,Tully, David C.
, p. 5129 - 5140 (2014/07/08)
A high throughput screening campaign identified 5-(2-chlorophenyl)indazole compound 4 as an antagonist of the transient receptor potential A1 (TRPA1) ion channel with IC50 = 1.23 μM. Hit to lead medicinal chemistry optimization established the SAR around the indazole ring system, demonstrating that a trifluoromethyl group at the 2-position of the phenyl ring in combination with various substituents at the 6-position of the indazole ring greatly contributed to improvements in vitro activity. Further lead optimization resulted in the identification of compound 31, a potent and selective antagonist of TRPA1 in vitro (IC50 = 0.015 μM), which has moderate oral bioavailability in rodents and demonstrates robust activity in vivo in several rodent models of inflammatory pain.
Quinoline derivatives or salt thereof and remedy for cardiac diseases containing the same
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, (2008/06/13)
A quinoline derivative represented by general formula (1), a medicinally acceptable salt thereof, and a remedy for cardiac diseases containing the same: STR1 [wherein ring A represents a furan, dihydrofuran or dioxolane ring, and R1 represents an aminoalkyl group]. The compound (1) has a positively inotropic effect on myocardia and an antiarrhythmic effect, and can dilate blood vessels without extremely increasing the heart rate. Therefore, a remedy for cardiac diseases containing the same as the active ingredient is remarkably useful for treating cardiac insufficiency, arrhythmia, and so forth.
