Mitchell Lorna, Wang Zhi, Hu Lain-Yen, Kostlan Catherine, Carroll Matthew, Dettling Danielle, Du Daniel, Pocalyko David, Wade Kimberly
Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, CT13 9QA, UK.
Bioorg Med Chem Lett. 2009 Mar 1;19(5):1310-3. doi: 10.1016/j.bmcl.2009.01.063. Epub 2009 Jan 27.
The first examples of thioether-substituted benzonitriles as potential soft-drug androgen receptor antagonists are reported. A number of 4-(alkylthio)- and of 4-(arylthio)-benzonitrile analogs were evaluated in human androgen receptor binding and cellular functional assays. Analogs with potent in vitro binding and cellular activities were evaluated for topical in vivo efficacy in the Golden Syrian hamster ear model. Analogs from both the 4-(alkylthio)- and of 4-(arylthio)-benzonitrile series showed moderate reduction of wax esters in vivo.
报道了硫醚取代苯甲腈作为潜在软药雄激素受体拮抗剂的首批实例。对多种4-（烷硫基）-和4-（芳硫基）-苯甲腈类似物进行了人雄激素受体结合和细胞功能测定。对具有强效体外结合和细胞活性的类似物在金黄叙利亚仓鼠耳部模型中进行了局部体内疗效评估。4-（烷硫基）-和4-（芳硫基）-苯甲腈系列的类似物在体内均显示出蜡酯含量适度降低。
