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 Receptor Antagonist
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 Receptor Antagonist
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DOI：
10.1021/jm8012932
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发表时间：
2009-01-22
影响因子：
7.3
通讯作者：
Scott, Dennis O.
中科院分区：
文献类型：
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作者：
Griffith, David A.;Hadcock, John R.;Scott, Dennis O.
我们报告了新型大麻素 1 型 (CB1) 受体拮抗剂 3a (CP-945,598) 的构效关系、设计和合成。化合物 3a 在人类 CB1 受体结合 (K-i = 0.7 nM) 和功能测定 (K-i = 0.12 nM) 中显示出亚纳摩尔效力。在体内，化合物 3a 逆转了大麻素激动剂介导的反应，减少了啮齿动物的食物摄入量，增加了能量消耗和脂肪氧化。
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.