2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor agonists. Part 2: orally bioavailable compounds.
Structure-activity relationships and efforts to optimize the pharmacokinetic profile of a class of 2-arylimino-5,6-dihydro-4H-1,3-thiazines as cannabinoid receptor agonists are described. Among the compounds examined, compound 14 showed potent affinity and high selectivity for CB2, and compound 23 showed potent affinities against CB1 and CB2. These compounds displayed oral bioavailability.
Kai
Hiroyuki
H
Shionogi Research Laboratories, Shionogi & Co. Ltd, 12-4, Sagisu 5-chome, Osaka 553-0002, Japan. hiroyuki.kai@shionogi.co.jp
Morioka
Yasuhide
Y
Tomida
Minoru
M
Takahashi
Tadashi
T
Hattori
Maki
M
Hanasaki
Kohji
K
Koike
Katsumi
K
Chiba
Hiroki
H
Shinohara
Shunji
S
Kanemasa
Toshiyuki
T
Iwamoto
Yuka
Y
Takahashi
Kohji
K
Yamaguchi
Yoshitaka
Y
Baba
Takahiko
T
Yoshikawa
Takayoshi
T
Takenaka
Hideyuki
H
D000284:Administration, Oral; D001682:Biological Availability; D063386:Cannabinoid Receptor Agonists; D013843:Thiazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*
D063386:Cannabinoid Receptor Agonists; D013843:Thiazines