Abstract
Previous pharmacological results have suggested that members of the heterocyclic bicyclo[3.3.1]nonan-9-one-like compounds are potent κ-opioid receptor specific agonists. One lead molecule of this series, called compound 1 (dimethyl 7-methyl-2,4-di-2-pyridyl-3,7-diazabicyclo[3.3.1]nonan-9-one-1,5-dicarboxylate) exhibited high affinity for [3H]ethylketocyclazocine and [3H]U-69,593 binding sites in guinea pig cerebellar membranes which known to be a good source for κ1 receptors. It was shown by molecular modelling that heterocyclic bicyclo[3.3.1]nonan-9-ones fit very well with the structure of ketazocine, a prototypic κ-selective benzomorphan compound; when compared to the arylacetamide structure of U-69,593, a specific κ1-receptor agonist, a similar geometry was found with a slightly different distribution of the charges. It is postulated, that the essential structural skeleton involved in the opioid activity is an aryl-propyl-amine element distributed along the N7-C6-C5-C4-aryl bonds.
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Financial supports provided by OTKA T035211 (S.B.), OTKA T032907 and NKFP 1/027 (A.B.) grants from the Hungarian Scientific Research Fund and from the Ministry of Education, Budapest, Hungary are greatly appreciated.
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Dedicated to Professor Maria Wollemann on the occasion of her 80th birthday.
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Benyhe, S., Márki, Á., Nachtsheim, C. et al. Kappa-Receptor Selective Binding of Opioid Ligands with a Heterocyclic Bicyclo[3.3.1]nonan-9-One Structure. BIOLOGIA FUTURA 54, 147–155 (2003). https://doi.org/10.1556/ABiol.54.2003.2.3
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DOI: https://doi.org/10.1556/ABiol.54.2003.2.3