Novel and potent small-molecule urotensin II receptor agonists

Research output: Contribution to journalArticle

Abstract

A series of analogs of the non-peptidic urotensin II receptor agonist N-[1-(4-chlorophenyl)-3-(dimethylamino)propyl]-4-phenylbenzamide (FL104) has been synthesized and evaluated pharmacologically. The enantiomers of the two most potent racemic analogues were obtained from the corresponding diastereomeric mandelic amides. In agreement with previously observed SAR, most of the agonist potency resided in the (S) enantiomers. The most potent UII receptor agonist in the new series was (S)-N-[3-dimethylamino-1-(2-naphthyl)propyl]-4-(4-chlorophenyl)benzamide (EC 50 = 23 nM at the urotensin II receptor).

Details

Authors
  • Fredrik Lehmann
  • Erika A. Currier
  • Bryan Clemons
  • Lars K. Hansen
  • Roger Olsson
  • Uli Hacksell
  • Kristina Luthman
External organisations
  • University of Gothenburg
  • ACADIA Pharmaceuticals Inc.
  • ACADIA Pharmaceuticals AB
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medicinal Chemistry

Keywords

  • Agonists, Parallel synthesis, R-SAT, SAR, Urotensin II
Original languageEnglish
Pages (from-to)4657-4665
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number13
Publication statusPublished - 2009 Jul 1
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes