Discovery of S-444823, a potent CB1/CB2 dual agonist as an antipruritic agent
- 作者：Masahide Odan ; masahide.oodan@shionogi.co.jp ; Natsuki Ishizuka ; Yoshiharu Hiramatsu ; Masanao Inagaki ; Hiroshi Hashizume ; Yasuhiko Fujii ; Susumu Mitsumori ; Yasuhide Morioka ; Masahiko Soga ; Masashi Deguchi ; Kiyoshi Yasui ; Akinori Arimura
- 关键词：Cannabinoid ; CB receptor agonist ; GPCR ; Antipruritics
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2012
- 期刊代码：10_0960894x
- 类别：ch
- 出版时间：15 April, 2012
- 卷：22
- 期：8
- 页码：2898-2901
- 文件大小：718 K
摘要
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.