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.
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.
Kai
Hiroyuki
H
Shionogi Research Laboratories, Shionogi & Co., Ltd, 12-4, Sagisu 5-chome, Fukushima-ku, Osaka 553-0002, Japan. hiroyuki.kai@shionogi.co.jp
Morioka
Yasuhide
Y
Koriyama
Yuji
Y
Okamoto
Kazuya
K
Hasegawa
Yasushi
Y
Hattori
Maki
M
Koike
Katsumi
K
Chiba
Hiroki
H
Shinohara
Shunji
S
Iwamoto
Yuka
Y
Takahashi
Kohji
K
Tanimoto
Norihiko
N
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
D063386:Cannabinoid Receptor Agonists; D013843:Thiazines; D013890:Thiourea