75785-11-4Relevant academic research and scientific papers
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.
HETEROCYCLIC NON-PEPTIDE GNRH ANTAGONISTS
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Page/Page column 72, (2008/06/13)
A compound of formula (I): wherein either B is absent and A and Z are the same or different and are each hydrogen, halogen, alkyl, hydroxy, alkoxy,-CN,-C(Rc)2OH,-N(Rd)C(=X)Rc,-C(=X)N(Rc)(Rd),-S(O)m-Rc,-N(Rc)(Rd)S(O)2,-S(O)2N(R c)(Rd),-N(Re)2, aryl optionally substituted with Ra or-O-aryl optionally substituted with Ra; or B is present and is-(CH2)n-,-C(Rb)2-or-O-, or B taken together with A or Z can be-C=C(Rb)-,-C(Rb)=C-,-CH2-CH(R b)-or-CH(Rb)-CH2-; D is-O-or-S(O) m,-; E is a bond or is-(CH2)n-,-N(R d)-,-(CH2)nN(Rd)-or-N(R d)(CH2)n-; F is-C(=X)-; G is-(CH2 )n-,-N(Rd)-,-(CH2)nN(R d)-or-N(Rd)(CH2)n; J is a bond,-O-,-N(RC)C(=X)-,-C(=X)N(Rc)-,-S(O)m,-,-N(Rc)S(O)m-,-S(O)nN(Rc)-,-N(Re)-or-N(Rg)(Rh); K is a bond, alkylene, cycloalkylene, cycloalkenylene, arylene, heterocycloalkylene, heterocycloalkylene or heteroarylene; and L is hydrogen or a terminal group; has therapeutic utility.
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.
