含二苯醚结构的芬戈莫德类似物的设计、合成及其生物活性研究

Design, synthesis and biological evaluation of fingolimod analogues containing diphenyl ether moiety

本文通过对已上市的治疗多发硬化症的免疫抑制剂芬戈莫德的结构改造,设计合成了一系列含有二苯醚结构的芬戈莫德类似物。通过体内动物实验对化合物的免疫抑制活性和心脏毒性进行了评价。结果表明,大多数化合物具有一定的免疫抑制活性,其中化合物6c、6d、14c^14e体内免疫抑制活性与阳性药芬戈莫德相当,化合物14e没有心动过缓副作用。

A novel series of fingolimod analogues containing diphenyl ether moiety were designed and synthesized based on the modification of immunosuppressive agent fingolimod used in the treatment of multiple sclerosis. Compounds were evaluated in vivo for lymphopenic activity and heart rate affection. Most compounds showed moderate lymphopenic activity. It is worth noting that compounds 6c, 6d and 14c-14e showed considerable immunosuppressive activities comparable to fingolimod. And compound 14e had no effect on heart rate.