Discovery of 1-[9-(4-Chlorophenyl)-8-(2-chlorophenyl)-9H-purin-6-yl]-4-ethylaminopiperidine-4-carboxylic Acid Amide Hydrochloride (CP-945,598), a Novel, Potent, and Selective Cannabinoid Type 1

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• 作者：David A. Griffith ; John R. Hadcock ; Shawn C. Black ; Philip A. Iredale ; Philip A. Carpino ; Paul DaSilva-Jardine ; Robert Day ; Joseph DiBrino ; Robert L. Dow ; Margaret S. Landis ; Rebecca E. O’ ; Connor
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：January 22, 2009
• 年：2009
• 卷：52
• 期：2
• 页码：234-237
• 全文大小：152K
• 年卷期：v.52,no.2(January 22, 2009)
• ISSN：1520-4804

文摘

We report the structure−activity relationships, design, and synthesis of the novel cannabinoid type 1 (CB₁) receptor antagonist 3a (CP-945,598). Compound 3a showed subnanomolar potency at human CB₁ receptors in binding (K_i = 0.7 nM) and functional assays (K_i = 0.12 nM). In vivo, compound 3a reversed cannabinoid agonist-mediated responses, reduced food intake, and increased energy expenditure and fat oxidation in rodents.