Synthesis and opioid receptor activity of indolopropellanes
Fuying Li1, Linghuan Gaob, Chenlei Yin
1Synthetic Organic and Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Abstract:
A series of skeletal rearranged indolomorphinans 7a-d were obtained by N-demethylation of 3-methoxy-N-methyl-14-hydroxymorphinan-6-one 12 followed by N-realkylation, reduction and Fischer indole cyclization. The structure of the novel skeleton was confirmed by X-ray analysis. These new indoles displayed moderate binding affinity and selectivity at the mu receptor, with compound 7b showing the highest affinity at this receptor with a K(i) value of 40nM, and 6- and 25-fold selectivity against delta and kappa receptors, respectively. Function assays showed that indolopropellanes 7b and 7c possessed full agonistic activity at all the opioid receptors indicating a different interaction model existed.
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