title: Design and synthesis of novel opioid ligands with an azabicyclo[2.2.2]octane skeleton and their pharmacologies.
abstract: A novel opioid ligand possessing a stable and cyclic imine 16 and its derivatives with an azabicyclo[2.2.2]octane skeleton were synthesized. The imine 16 showed higher affinity for the μ receptor than compound 21 with an oxabicyclo[2.2.2]octane skeleton. Azabicyclo[2.2.2]octane derivative 18d with a cyclopropylmethyl group on the 8-nitrogen showed the highest affinity for the μ receptor among the synthesized derivatives.
authors.affiliation: School of Pharmacy, Kitasato University, Tokyo, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Shota
authors.initials: S
authors.lastname: Kitazawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujii
authors.forename: Toru
authors.initials: T
authors.lastname: Nemoto
authors.forename: Shigeto
authors.initials: S
authors.lastname: Hirayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagase
mesh_terms: D000701:Analgesics, Opioid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D008024:Ligands; D015394:Molecular Structure; D009019:Morphinans / Q000737:chemistry / Q000494:pharmacology; D009795:Octanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011957:Receptors, Opioid / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000701:Analgesics, Opioid; D001372:Aza Compounds; D001643:Bridged Bicyclo Compounds; D008024:Ligands; D009019:Morphinans; D009795:Octanes; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D013141:Spiro Compounds; C111212:TRK 820; C026728:octane