Renovis, Inc, South San Francisco, CA 94080, USA.
Bioorg Med Chem Lett. 2009 Dec 1;19(23):6793-6. doi: 10.1016/j.bmcl.2009.09.086. Epub 2009 Sep 30.
The screening of known medicinal agents against new biological targets has been shown to be a valuable approach for revealing new pharmacology of marketed compounds. Recently, carbamate, urea and ketone inhibitors of fatty acid amide hydrolase (FAAH) have been described as promising treatments for pain, anxiety, depression and other CNS-related conditions. In order to find novel FAAH inhibitors, a focused screen of molecules containing potentially reactive moieties or having in vivo effects that are possibly relevant to the biology of FAAH was conducted. These studies revealed phenmedipham 13 and amperozide 14 to be inhibitors of human FAAH, with an IC(50) of 377 nM and 1.34 microM, respectively.
针对新的生物靶点筛选已知的药物制剂已被证明是揭示市售化合物新药理学的一种有价值的方法。最近，脂肪酸酰胺水解酶（FAAH）的氨基甲酸酯、脲和酮抑制剂已被描述为治疗疼痛、焦虑、抑郁和其他中枢神经系统相关疾病的有希望的药物。为了寻找新型 FAAH 抑制剂，对含有潜在反应性部分的分子或具有可能与 FAAH 生物学相关的体内作用的分子进行了有针对性的筛选。这些研究表明，苯甲氢氨 13 和氨普哚嗪 14 是人类 FAAH 的抑制剂，IC50 分别为 377 nM 和 1.34 μM。
