Facile synthesis of octahydrobenzo[h]isoquinolines: novel and highly potent D1 dopamine agonists

Abstract

The octahydrobenzo[h]isoquinoline scaffold is of interest as a conformationally-restricted phenethylamine that may be useful for constructing biologically active products. Surprisingly, however, no tractable synthesis of this ring system has been reported. We now describe a facile method for obtaining this framework, and illustrate that our approach is easily amenable to substitutions at the 5-position. Importantly, we demonstrate that the 7,8-dihydroxy-5-phenyl-substituted ligand is an extremely potent, high-affinity, full D1 dopamine receptor-selective agonist.