Identification of a 2-phenyl-substituted octahydrobenzo[f]quinoline as a dopamine D₃ receptor-selective full agonist ligand. Bioorg Med Chem 2012 Nov 01;20(21):6366-74
Date
09/29/2012Pubmed ID
23018094Pubmed Central ID
PMC3505999DOI
10.1016/j.bmc.2012.08.058Scopus ID
2-s2.0-84867577564 (requires institutional sign-in at Scopus site) 9 CitationsAbstract
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.
Author List
Clark AH, McCorvy JD, Conley JM, Williams WK, Bekkam M, Watts VJ, Nichols DEAuthor
John McCorvy PhD Associate Professor in the Cell Biology Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Binding, CompetitiveCells, Cultured
Dose-Response Relationship, Drug
HEK293 Cells
Humans
Ligands
Models, Molecular
Molecular Conformation
Quinolines
Receptors, Dopamine D3
Structure-Activity Relationship
