title: Synthesis of new opioid derivatives with a propellane skeleton and their pharmacologies: part 3, novel propellane derivatives with pentacyclic skeletons.
abstract: Previously reported propellane derivative KNT-42 preferred the κ receptor and functioned as a message part in the message-address concept, but its affinity for the κ receptor was not high. To improve affinity, we synthesized five pentacyclic propellane derivatives designed for the purpose of fixing the conformation of KNT-42. The etheno- and ethano-bridged derivatives SYK-347 and SYK-393 exhibited high affinity and selectivity for the κ receptor, whereas the other derivatives did not. These results would be due to the different ranges of movement of the basic nitrogens and less basicity of the nitrogens due to the electron withdrawing effect of the introduced hydroxy or keto group. SYK-347 and SYK-393 preferring the κ receptor were expected to be useful for designing selective ligands for opioid receptor types, especially the κ receptor.
authors.affiliation: Laboratory of Medicinal Chemistry, School of Pharmacy, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujii
authors.forename: Ryo
authors.initials: R
authors.lastname: Nakajima
authors.forename: Junko
authors.initials: J
authors.lastname: Akiyama
authors.forename: Naoshi
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Shigeto
authors.initials: S
authors.lastname: Hirayama
authors.forename: Toru
authors.initials: T
authors.lastname: Nemoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Gouda
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hirono
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagase
mesh_terms: D000701:Analgesics, Opioid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D051379:Mice; D008968:Molecular Conformation; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D000701:Analgesics, Opioid; D001952:Bridged-Ring Compounds; D017473:Receptors, Opioid, kappa