Yang Shu-Wei, Ho Ginny, Tulshian Deen, Greenlee William J, Tan Zheng, Zhang Hongtao, Smith-Torhan April, Fawzi Ahmad, Anthes John, Lu Sherry, Varty Geoffrey, Fernandez Xiomara, McLeod Robbie L, Hey John
Department of Chemical Research-CV & CNS, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Bioorg Med Chem Lett. 2009 May 1;19(9):2482-6. doi: 10.1016/j.bmcl.2009.03.057. Epub 2009 Mar 18.
A series of nortropane analogs based on previously reported compound 1 have been synthesized and shown to bind to the nociceptin receptor with high affinity. The synthesis and structure-activity relationships around the C-3 nortropane substitution are described. From the SAR study and hPXR screening effort, compound 15 was identified to possess potent oral antitussive and anxiolytic-like activities in the guinea pig models.
基于先前报道的化合物1合成了一系列降托烷类似物，结果表明它们与孤啡肽受体具有高亲和力。本文描述了C-3降托烷取代基周围的合成及构效关系。通过构效关系研究和人孕烷X受体筛选工作，确定化合物15在豚鼠模型中具有有效的镇咳和抗焦虑样活性。
