Discovery of S-444823, a potent CB1/CB2 dual agonist as an antipruritic agent

被引：9

作者：

Odan, Masahide ^{[1
]}

Ishizuka, Natsuki ^{[1
]}

Hiramatsu, Yoshiharu ^{[1
]}

Inagaki, Masanao ^{[1
]}

Hashizume, Hiroshi ^{[1
]}

Fujii, Yasuhiko ^{[1
]}

Mitsumori, Susumu ^{[1
]}

Morioka, Yasuhide ^{[1
]}

Soga, Masahiko ^{[1
]}

Deguchi, Masashi ^{[1
]}

Yasui, Kiyoshi ^{[1
]}

Arimura, Akinori ^{[1
]}

机构：

[1] Shionogi & Co Ltd, Shionogi Pharmaceut Res Ctr, Toyonaka, Osaka 5610825, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 08期

关键词：

Cannabinoid; CB receptor agonist; GPCR; Antipruritics; CANNABINOID RECEPTOR; EXPRESSION; TARGET; BRAIN; CB1;

D O I：

10.1016/j.bmcl.2012.02.050

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

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. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：2898 / 2901

页数：4

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