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

Previously 2,4-dipyridine substituted 3,7-diazabicyclo[3.3.1]nonanone diest ers were found to have a high affinity and selectivity towards the kappa-op ioid receptor. The purpose of this study was to check the influence of subs tituents at position N3 on the affinity to the mu-, delta-, and kappa-recep tors. Whereas a phenylethyl group is able to create affinity to the mu-rece ptor, small substituents such as;a hydrogen or a methyl group are responsib le for a high affinity to the kappa-receptor. In addition, a dimeric compou nd 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 t he blood-brain barrier.