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