Diazabicyclo[3.3.1]nonanone-type ligands for the opioid receptors.

Previously 2,4-dipyridine substituted 3,7-diazabicyclo[3.3.1]nonanone diesters were found to have a high affinity and selectivity towards the kappa-opioid receptor. The purpose of this study was to check the influence of substituents at position N3 on the affinity to the mu-, delta-, and kappa-receptors. Whereas a phenylethyl group is able to create affinity to the mu-receptor, small substituents such as a hydrogen or a methyl group are responsible for a high affinity to the kappa-receptor. In addition, a dimeric compound was found to have affinity to the kappa-receptor. Although all compounds will bear at least one positive charge under physiological conditions they show a considerable lipophilicity, indicating the possibility of passing the blood-brain barrier.