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.
Kuhl
U
U
Institut für Pharmazie und Lebensmittelchemie, Universität Würzburg, Germany.
Englberger
W
W
Haurand
M
M
Holzgrabe
U
U
D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001923:Brain Chemistry; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism*
D000700:Analgesics; D001643:Bridged Bicyclo Compounds; D007659:Ketones; D008024:Ligands; D011725:Pyridines; D011957:Receptors, Opioid