Identification of a 2-phenyl-substituted octahydrobenzo[f]quinoline as a dopamine D₃ receptor-selective full agonist ligand

  • Bioorg Med Chem. 2012 Nov 1;20(21):6366-74. doi: 10.1016/j.bmc.2012.08.058.
Alia H Clark  1 ,  John D McCorvy ,  Jason M Conley ,  Whitney K Williams ,  Markondaiah Bekkam ,  Val J Watts ,  David E Nichols
Affiliations
  • 1. Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy and Integrative Neuroscience Program, Purdue University, West Lafayette, IN 47907, USA.
PMID: 23018094 DOI: 10.1016/j.bmc.2012.08.058
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.