Synthesis and opioid receptor activity of indolopropellanes |
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| Authors: | Fuying Li Linghuan Gaob Chenlei Yin Jie Chen Jinggen Liu Xin Xie Ao Zhang |
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| Affiliation: | 1. Synthetic Organic and Medicinal Chemistry Laboratory (SOMCL), Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China;2. National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;3. Neuropharmacological Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China |
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| 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 μ receptor, with compound 7b showing the highest affinity at this receptor with a Ki value of 40 nM, and 6- and 25-fold selectivity against δ and κ 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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