有机合成在创新药物研发中的应用与进展.pdf

DOI: 10.6023/cjoc201408007 综述与进展 有机化学 Chinese Journal of Organic Chemistry REVIEW 有机合成在创新药物研发中的应用与进展 张 霁* 聂 飚 张英俊 (广东东阳光集团药业研究院 东莞 523871) 摘要 论述了现代有机合成化学在一些创新药物尤其是“重磅炸弹”新药, 如索非布韦(Sofosbuvir) 、利伐沙班 (Rivaroxaban)、恩杂鲁胺(Enzalutamide)、卡格列净(Canagliflozin)和托法替尼(Tofacitinib), 研发中的应用和进展, 突出 显示了催化过程、闭环复分解反应、钯催化的交叉偶联、绿色化学和叠缩工艺等合成方法. 通过数十个新分子实体药 物发明历程的回顾, 诠释了现代有机合成在新药开发中的重要作用. 关键词 药物; 药物合成; 有机合成; 合成艺术 Application and Progress of Organic Synthesis in the Discovery of Innovative Drugs Zhang, Ji* Nie, Biao Zhang, Yingjun (HEC Pharm Group, HEC RD Center, Dongguan 523871) Abstract This article reviews the application and progress of modern synthetic methods to deliver several innovative drugs, especially the blockbusters, such as sofosbuvir, rivaroxaban, enzalutamide, canagliflozin and tofacitinib. Some of the modern synthetic methods, for example catalytic processes, application of ring-closing metathesis, palladium catalyzed cross-coupling, green chemistry and telescoping of processes, are highlighted. The exciting journey from discovering these new molecular entities, especially those which are first-in-class with the synthesis of a dozen of approved drugs, is described as case studies to fully illustrate the important role of modern organic synthesis for successful drug discovery and development. Keywords drugs; drug synthesis; organic synthesis; art in drug synthesis