Discovery of benzhydrylpiperazine derivatives as CB₁ receptor inverse agonists via privileged structure-based approach

详细信息    查看全文

• 作者：Tao Meng ; Jue Wang ; Hongli Peng ; Guanghua Fang ; Min Li ; Bing Xiong ; Xin Xie ; Yongliang Zhang ; Xin Wang ; Jingkang Shen
• 关键词：Benzhydrylpiperazine ; Privileged structure ; Cannabinoid receptor 1(CB₁) ; Anti-obesity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：March 2010
• 年：2010
• 卷：45
• 期：3
• 页码：1133-1139
• 全文大小：680 K

文摘

The present study describes the identification via privileged structure-based approach of the benzhydrylpiperazine moiety as a potential scaffold to develop novel CB₁ receptor modulators. Efficient structural optimization of the initial four hit compounds led to a high quality lead series, represented by compound 6c. Compound 6c is a highly potent and selective CB₁ receptor inverse agonist that is able to reduce body weight in diet-induced obese Sprague–Dawley rats. The preparation of privileged structure-based library, the progression from hit to lead, the structure–activity relationships in the lead series and in vitro and in vivo activity of compound 6c are discussed.