title: Discovery of S-444823, a potent CB1/CB2 dual agonist as an antipruritic agent.
abstract: The optimization of a series of 3-carbamoyl 2-pyridone derivatives as CB agonists is reported. These efforts resulted in the discovery of 3-(2-(1-(cyclohexylmethyl)-2-oxo-1,2,5,6,7,8,9,10-octahydrocycloocta[b]pyridine-3-carboxamido)thiazol-4-yl)propanoic acid (21), a potent dual CB1/CB2 agonist without CNS side effects induced by CB1 receptor activation. It exhibited strong inhibition of scratching as a 1.0% acetone solution in the pruritic model.
authors.affiliation: Shionogi Pharmaceutical Research Center, Shionogi & Co., Ltd, 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; D016466:CHO Cells; D006224:Cricetinae; D055808:Drug Discovery; D006801:Humans; D051379:Mice; D011485:Protein Binding / Q000187:drug effects; D011728:Pyridones / Q000819:agonists* / Q000737:chemistry / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists*; D013844:Thiazoles / Q000819:agonists* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000982:Antipruritics; D011728:Pyridones; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C574959:S-444823; D013844:Thiazoles