کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1366683 | 981600 | 2007 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Optimization of imidazole amide derivatives as cannabinoid-1 receptor antagonists for the treatment of obesity Optimization of imidazole amide derivatives as cannabinoid-1 receptor antagonists for the treatment of obesity](/preview/png/1366683.png)
Several imidazole-based cyclohexyl amides were identified as potent CB-1 antagonists, but they exhibited poor oral exposure in rodents. Incorporation of a hydroxyl moiety on the cyclohexyl ring provided a dramatic improvement in oral exposure, together with a ca. 10-fold decrease in potency. Further optimization provided the imidazole 2-hydroxy-cyclohexyl amide 45, which exhibited hCB-1 Ki = 3.7 nM, and caused significant appetite suppression and robust, dose-dependent reduction of body weight gain in industry-standard rat models.
Imidazole-based cyclohexyl amides were identified as potent CB-1 antagonists. Incorporation of a hydroxyl moiety on the cyclohexyl ring provided a dramatic improvement in oral exposure in rodents, and further optimization provided 45, which caused significant appetite suppression and robust, dose-dependent reduction of body weight gain in industry-standard rat models.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 17, Issue 10, 15 May 2007, Pages 2706–2711