Discovery of the first nonpeptide agonist of the GPR14/urotensin-II receptor: 3-(4-chlorophenyl)-3-(2- (dimethylamino)ethyl)isochroman-1-one (AC-7954).

Glenn E Croston, Roger Olsson, Erika A Currier, Ethan S Burstein, David Weiner, Norman Nash, Daniel Severance, Stig G Allenmark, Linda Thunberg, Jian-Nong Ma, Nina Mohell, Brian O'Dowd, Mark R Brann, Uli Hacksell

文献索引：J. Med. Chem. 45 , 4950-4953, (2002)

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摘要

A functional cell-based screen identified 3-(4-chlorophenyl)-3-(2-(dimethylamino)ethyl)isochroman-1-one hydrochloride (AC-7954, 1) as a nonpeptidic agonist of the urotensin-II receptor. Racemic 1 had an EC50 of 300 nM at the human UII receptor and was highly selective. Testing of the enantiopure (+)- and (-)- 1 revealed that the UII receptor activity of racemic 1 resides primarily in (+)-1. Being a selective nonpeptidic druglike UII receptor agonist, (+)-1 will be useful as a pharmacological research tool and a potential drug lead.