Novel and potent small-molecule urotensin II receptor agonists.
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).
Lehmann
Fredrik
F
Department of Chemistry, Medicinal Chemistry, University of Gothenburg, Göteborg, Sweden.
Currier
Erika A
EA
Clemons
Bryan
B
Hansen
Lars K
LK
Olsson
Roger
R
Hacksell
Uli
U
Luthman
Kristina
K
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
D001549:Benzamides; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human