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

  • J Med Chem. 2002 Nov 7;45(23):4950-3. doi: 10.1021/jm025551+.
Glenn E Croston  1 ,  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
Affiliations
  • 1. ACADIA Pharmaceuticals Inc., 3911 Sorrento Valley Boulevard, San Diego, California 92121, USA.
PMID: 12408704 DOI: 10.1021/jm025551+
Abstract

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.

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