title: Identification of a 2-phenyl-substituted octahydrobenzo[f]quinoline as a dopamine D₃ receptor-selective full agonist ligand.
abstract: This work describes the identification of a novel class of octahydrobenzo[f]quinolines as dopamine D(3)-selective full agonists. We developed a facile method that utilizes Suzuki coupling for easy incorporations of various substituted pendant rings into the scaffold. A small focused library of octahydrobenzo[f]quinolines 5 was synthesized, and these compounds demonstrated at least 14-fold D(2)-like selectivity over D(1) in native porcine striatal tissue. Furthermore, n-propyl analog 5f was found to be a high affinity (K(i)=1.1 nM) D(3) dopamine full agonist with 145-fold selectivity over the D(2) receptor and about 840-fold selectivity over the D(1) receptor.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy and Integrative Neuroscience Program, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Alia H
authors.initials: AH
authors.lastname: Clark
authors.forename: John D
authors.initials: JD
authors.lastname: McCorvy
authors.forename: Jason M
authors.initials: JM
authors.lastname: Conley
authors.forename: Whitney K
authors.initials: WK
authors.lastname: Williams
authors.forename: Markondaiah
authors.initials: M
authors.lastname: Bekkam
authors.forename: Val J
authors.initials: VJ
authors.lastname: Watts
authors.forename: David E
authors.initials: DE
authors.lastname: Nichols
mesh_terms: D001667:Binding, Competitive / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D050637:Receptors, Dopamine D3 / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D011804:Quinolines; D050637:Receptors, Dopamine D3; C579454:octahydrobenzo(f)quinoline