2-Arylimino-5,6-dihydro-4H-1,3-thiazines as a new class of cannabinoid receptor agonists. Part 1: discovery of CB2 receptor selective compounds.
2-Arylimino-5,6-dihydro-4H-1,3-thiazines have been identified as a novel class of cannabinoid agonists. A lead structure with moderate activity was discovered through a high throughput screening assay. Structure-activity relationships led to the discovery of potent agonists of CB(2) receptor. The most potent compound 13 displays K(i) values of >5000 and 9 nM to CB(1) and CB(2) receptors, respectively.
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
Murashi
Takami
T
Morita
Koichi
K
Shinonome
Satomi
S
Nakazato
Hitoshi
H
Kawamoto
Keiko
K
Hanasaki
Kohji
K
Takahashi
Fumiyo
F
Mihara
Shin-ichi
S
Arai
Tohko
T
Abe
Kohji
K
Okabe
Hiroshi
H
Baba
Takahiko
T
Yoshikawa
Takayoshi
T
Takenaka
Hideyuki
H
D000818:Animals; D063386:Cannabinoid Receptor Agonists; D051381:Rats; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
D063386:Cannabinoid Receptor Agonists; D013843:Thiazines