title: Design and synthesis of novel opioid ligands with an azabicyclo[2.2.2]octane skeleton having a 7-amide side chain and their pharmacologies.
abstract: Several derivatives with an azabicyclo[2.2.2]octane skeleton having a 7-amide side chain were synthesized. Compounds that had an electron-donating group exhibited high affinity for the μ opioid receptor while those with a bulky substituent at the 8-nitrogen atom had low affinities for all receptor types. High affinities and selectivities for the κ receptor resulted from the introduction of the longer amide side chain at the 7α-position. Our studies indicate that the orientation of the amide side chain at the 7-position within the azabicyclo[2.2.2]octane skeleton is related to selectivity for the κ receptor.
authors.affiliation: School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Shota
authors.initials: S
authors.lastname: Kitazawa
authors.forename: Toru
authors.initials: T
authors.lastname: Nemoto
authors.forename: Shigeto
authors.initials: S
authors.lastname: Hirayama
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwai
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujii
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagase
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000737:chemistry; D053961:Azabicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D001681:Biological Assay; D015195:Drug Design; D006801:Humans; D008024:Ligands; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000737:chemistry*; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000737:chemistry*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000701:Analgesics, Opioid; D053961:Azabicyclo Compounds; D008024:Ligands; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu