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.