抗丙型肝炎药物索磷布韦的设计合成研究进展

Design and synthesis of anti-HCV drug sofosbuvir:research advances

索磷布韦(sofosbuvir)是治疗丙型肝炎的一种新类型的直接作用抗病毒药物,通过竞争性结合到NS5B聚合酶活性位点,导致新生病毒基因组合成的终止,从而抑制丙型肝炎病毒(HCV)的复制。该药的开发过程是基于核苷类抗病毒药物的体内代谢原理,通过巧妙的结构修饰,改善了药物结构稳定性和吸收过程,使其最终发展成为肝靶向抗HCV药物。索磷布韦单用或联用其他抗HCV药物用于治疗丙型肝炎,具有治愈率高、安全性高、且不易产生耐药性的优点,已经成为临床基础用药。本文主要对索磷布韦的研究背景、临床应用、开发过程及其制备方法等进行综述。

Sofosbuvir is a new type of direct-acting antiviral（DAA）drugs against hepatitis C. By competitive combination to NS5 B polymerase activity sites,sofosbuvir can terminate genome synthesis of newly born virus,and finally inhibit the replication of hepatitis C virus（HCV）. The research and development process of sofosbuvir is based on the principles of nucleoside antiviral drug metabolism. The subtle structure modification improves the drug′s structure stability and absorption process,which makes sofosbuvir a liver targeted anti-HCV drug. Sofosbuvir has become a clinical fundamental drug for anti-HCV infection,and then used alone or in combination with other drugs,with higher recovery rate,better safety and anti-drug resistance. This article reviews the research background,development process,clinical application and synthetic methods for sofosbuvir.