Synthesis of Novel 4-Aryl-1,2,3,4-tetrahydroisoquinolines as Probes for Dopamine Receptor Ligands

Gianfabio      Giorgioni; Dario      Ambrosini; Giovanni      Filippo Palmieri; Barbara      Costa; Antonio      Di Stefano; Claudia      Martini

doi:10.2174/157340612801216292

Abstract

Dopamine (DA) agonists, bearing catechol or phenol rings, are endowed with low oral bioavailability and short effect duration. In this report, the synthesis of novel differently substituted 4-(3-pyridyl)-1,2,3,4-tetrahydroisoquinolines and (1,2,3,4-tetrahydroisoquinolin-4-yl)phenylmethanols as potential non phenolic and non catecholic DA receptor ligands is reported. The new compounds, evaluated by binding tests on cerebral striatal membranes, bound to DA receptors with moderate affinity. Anyhow, they may represent a starting point to develop new DA ligands endowed with better pharmacokinetic and metabolic properties.

Keywords: Binding tests, cross-coupling reactions, D1-like receptors, D2-like receptors, dopamine ligands, structure activity relationships, tetrahydroisoquinoline, pharmacokinetic, cerebral striatal membranes, phenylmethanols