title: CB 1/2 dual agonists with 3-carbamoyl 2-pyridone derivatives as antipruritics: reduction of CNS side effects by introducing polar functional groups.
abstract: Our lead compound 1 showed high affinity for both CB1 and CB2 receptors, suggesting the possibility of inducing psychoactive side effects through the CB1 receptor in the brain. To solve this issue, polar functional groups were introduced at the 3-position of the pyridone core of compound 1 to find CB1/2 dual agonists such as 17 and 20 which did not show any CNS side effects.
authors.affiliation: Shionogi Pharmaceutical Research Center, Shionogi & Co., Ltd. 1-1, Toyonaka, Osaka, Japan. masahide.oodan@shionogi.co.jp
authors.forename: Masahide
authors.initials: M
authors.lastname: Odan
authors.forename: Natsuki
authors.initials: N
authors.lastname: Ishizuka
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Hiramatsu
authors.forename: Masanao
authors.initials: M
authors.lastname: Inagaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hashizume
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Fujii
authors.forename: Susumu
authors.initials: S
authors.lastname: Mitsumori
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Morioka
authors.forename: Masahiko
authors.initials: M
authors.lastname: Soga
authors.forename: Masashi
authors.initials: M
authors.lastname: Deguchi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yasui
authors.forename: Akinori
authors.initials: A
authors.lastname: Arimura
mesh_terms: D000818:Animals; D000982:Antipruritics / Q000737:chemistry / Q000494:pharmacology; D001522:Behavior, Animal; D002219:Carbamates / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D011728:Pyridones / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*
chemical_list: D000982:Antipruritics; D002219:Carbamates; D011728:Pyridones; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2