Discovery of N-[(1S,2S)-3-(4-Chlorophenyl)-2- (3-cyanophenyl)-1-methylpropyl]-2-methyl-2- {[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide (MK-0364), a Novel, Acyclic Cannabinoid

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• 作者：Linus S. Lin ; Thomas J. Lanza ; Jr. ; James P. Jewell ; Ping Liu ; Shrenik K. Shah ; Hongbo Qi ; Xinchun Tong ; Junying Wang ; Suoyu S. Xu ; Tung M. Fong ; Chun-Pyn Shen ; Julie Lao ; Jing Chen Xiao ; Lauren P. Sh
• 刊名：Journal of Medicinal Chemistry
• 出版年：2006
• 出版时间：December 28, 2006
• 年：2006
• 卷：49
• 期：26
• 页码：7584 - 7587
• 全文大小：84K
• 年卷期：v.49,no.26(December 28, 2006)
• ISSN：1520-4804

文摘

The discovery of novel acyclic amide cannabinoid-1 receptorinverse agonists is described. They are potent, selective, orallybioavailable, and active in rodent models of food intake and body weightreduction. A major focus of the optimization process was to increasein vivo efficacy and to reduce the potential for formation of reactivemetabolites. These efforts led to the identification of compound 48 fordevelopment as a clinical candidate for the treatment of obesity.