title: Novel and potent small-molecule urotensin II receptor agonists.
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).
authors.affiliation: Department of Chemistry, Medicinal Chemistry, University of Gothenburg, Göteborg, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Lehmann
authors.forename: Erika A
authors.initials: EA
authors.lastname: Currier
authors.forename: Bryan
authors.initials: B
authors.lastname: Clemons
authors.forename: Lars K
authors.initials: LK
authors.lastname: Hansen
authors.forename: Roger
authors.initials: R
authors.lastname: Olsson
authors.forename: Uli
authors.initials: U
authors.lastname: Hacksell
authors.forename: Kristina
authors.initials: K
authors.lastname: Luthman
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D001549:Benzamides; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human