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Published on: August 16, 2018
Ring expansions of tetrahydroprotoberberines and related dibenzo[c,g]azecines modulate the dopamine receptor subtype
Maria Schulze1, Oliver Siol, Werner Meise
1Institut für Pharmazie, Lehrstuhl für Pharmazeutische/Medizinische Chemie, Friedrich-Schiller-Universität Jena, Jena, Germany.
Abstract:
The affinities of tetrahydroprotoberberines for dopamine receptors dramatically decrease after cleaving the central C-N bond to the analogous ten-membered dibenzo[c,g]azecines [1]. In the present work, we also synthesized eleven-membered homologues of these heterocycles and measured the affinities of the resulting dibenzazaundecenes and their underlying homoberberines for human dopamine receptors as well as the cytotoxic effects of all target compounds on human glia cells. The tetracyclic iso-C-homoberberine-derivatives revealed to be D(4)-selective antagonists, while all other active compounds showed a significant D(1)/D(5) selectivity. Distances in energy-minimized conformations were measured in order to explain our findings.
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