新型二取代环己基苯甲酰胺衍生物作为强效11β-羟类固醇脱氢酶1抑制剂的优化
Optimization of novel di-substituted cyclohexylbenzamide derivatives as potent 11 beta-HSD1 inhibitors.
作者信息
McMinn Dustin L, Rew Yosup, Sudom Athena, Caille Seb, Degraffenreid Michael, He Xiao, Hungate Randall, Jiang Ben, Jaen Juan, Julian Lisa D, Kaizerman Jacob, Novak Perry, Sun Daqing, Tu Hua, Ursu Stefania, Walker Nigel P C, Yan Xuelei, Ye Qiuping, Wang Zhulun, Powers Jay P
机构信息
Amgen, Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA.
出版信息
Bioorg Med Chem Lett. 2009 Mar 1;19(5):1446-50. doi: 10.1016/j.bmcl.2009.01.026. Epub 2009 Jan 15.
Novel 4,4-disubstituted cyclohexylbenzamide inhibitors of 11beta-HSD1 were optimized to account for liabilities relating to in vitro pharmacokinetics, cytotoxicity and protein-related shifts in potency. A representative compound showing favorable in vivo pharmacokinetics was found to be an efficacious inhibitor of 11beta-HSD1 in a rat pharmacodynamic model (ED(50)=10mg/kg).
对新型11β-羟基类固醇脱氢酶1（11β-HSD1）的4,4-二取代环己基苯甲酰胺抑制剂进行了优化，以解决与体外药代动力学、细胞毒性和蛋白相关的效价变化有关的问题。在大鼠药效学模型中，发现一种具有良好体内药代动力学的代表性化合物是11β-HSD1的有效抑制剂（半数有效剂量（ED50）=10mg/kg）。
Zotero 插件