title: 2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor agonists. Part 3: Synthesis and activity of isosteric analogs.
abstract: Structure-activity relationships and efforts to optimize the pharmacokinetic profile of isosteric analogs of 2-arylimino-5,6-dihydro-4H-1,3-thiazines as cannabinoid receptor agonists are described. Among those examined, compound 25 showed potent affinity for cannabinoid receptor 1 (CB1) and receptor 2 (CB2). This compound displayed oral bioavailability and analgesic activity.
authors.affiliation: Shionogi Research Laboratories, Shionogi & Co., Ltd, 12-4, Sagisu 5-chome, Fukushima-ku, Osaka 553-0002, Japan. hiroyuki.kai@shionogi.co.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kai
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Morioka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Koriyama
authors.forename: Kazuya
authors.initials: K
authors.lastname: Okamoto
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Maki
authors.initials: M
authors.lastname: Hattori
authors.forename: Katsumi
authors.initials: K
authors.lastname: Koike
authors.forename: Hiroki
authors.initials: H
authors.lastname: Chiba
authors.forename: Shunji
authors.initials: S
authors.lastname: Shinohara
authors.forename: Yuka
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Kohji
authors.initials: K
authors.lastname: Takahashi
authors.forename: Norihiko
authors.initials: N
authors.lastname: Tanimoto
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D063386:Cannabinoid Receptor Agonists; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D051379:Mice; D008956:Models, Chemical; D051381:Rats; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D013890:Thiourea / Q000737:chemistry
chemical_list: D063386:Cannabinoid Receptor Agonists; D013843:Thiazines; D013890:Thiourea