Title of article
Optimization of imidazole amide derivatives as cannabinoid-1 receptor antagonists for the treatment of obesity
Author/Authors
Roger A. Smith، نويسنده , , Zahra Fathi، نويسنده , , Furahi Achebe، نويسنده , , Christiana Akuche، نويسنده , , Su-Ellen Brown، نويسنده , , Soongyu Choi، نويسنده , , Jianmei Fan، نويسنده , , Susan Jenkins، نويسنده , , Harold C.E. Kluender، نويسنده , , Anish Konkar، نويسنده , , Rico Lavoie، نويسنده , , Ronald Mays، نويسنده , , Jennifer Natoli، نويسنده , , Stephen J. O’Connor، نويسنده , , Astrid A. Ortiz، نويسنده , , Ning Su، نويسنده , , Christy Taing، نويسنده , , Susan Tomlinson، نويسنده , , Theresa Tritto، نويسنده , , Gan Wang، نويسنده , , et al.، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2007
Pages
6
From page
2706
To page
2711
Abstract
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.
Keywords
Antagonist , Cannabinoid , obesity , Appetite suppressant
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2007
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
798108
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