Facile synthesis of octahydrobenzo[h]isoquinolines: novel and highly potent D1 dopamine agonists
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Updated: Jun 10, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Lisa A Bonner1, Benjamin R Chemel, Val J Watts
1Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, United States.
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.
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