摘要
磷酸酯类前药与原药相比,不仅能够提高药物靶向性、稳定性和生物利用度,减少药物毒副作用,还能掩蔽药物不适气味、提高水溶性从而改善给药途径。含羟基药物的磷酸酯化是该类药物前药设计的重要方法之一。本文根据中心磷原子的价态和化合物结构进行分类,综述了各种P(Ⅴ)四配位分子、P(Ⅲ)三配位分子和H-亚磷酸酯类化合物作为磷酸酯化试剂在磷酸酯类前药合成方法中的研究进展,并阐述了这些磷酸酯类药物的应用,最后总结了各类磷酸酯化试剂的优势与局限,并结合连续流反应技术应用案例展望了其发展趋势。
Compared with the original drugs, the phosphoester prodrugs can not only improve the targeting, stability and bioavailability of the drugs, reduce toxicity and side effects, but also mask the unpleasant odor of the drugs, improve water solubility, and provide better access to the drugs. Phosphorylation of hydroxyl-containing drugs is one of the most important methods for their prodrug design. According to different valences of central phosphorus atoms and chemical structures, the phosphorylation reagents include tetracoordinated P(Ⅴ) compounds, tricoordinated P(Ⅲ) compounds and H-phosphite esters. The advances of these reagents in the synthesis of phosphoester prodrugs were reviewed, and the applications of these prodrugs were elaborated. Finally, the advantages and limitations of various phosphorylation reagents were summarized, and the development trend was prospected based on the application cases of continuous flow reaction technology.
作者
龚智华
胡莎
金学平
余磊
朱园园
古双喜
Zhihua Gong;Sha Hu;Xueping Jin;Lei Yu;Yuanyuan Zhu;Shuangxi Gu(Key Laboratory for Green Chemical Process of Ministry of Education&Hubei Key Laboratory of Novel Reactor and Green Chemical Technology,School of Chemical Engineering and Pharmacy,Wuhan Institute of Technology,Wuhan 430205,China;Wuhan Drug Solubilization and Delivery Technology Research Center,Wuhan Vocational College of Software and Engineering,Wuhan 430205,China;School of Chemistry and Environmental Engineering,Wuhan Institute of Technology,Wuhan 430205,China)
出处
《化学进展》
SCIE
CAS
CSCD
北大核心
2022年第9期1972-1981,共10页
Progress in Chemistry
基金
国家自然科学基金项目(No.21877087,22074114,20602164)
湖北省自然科学基金项目(No.2020CFB623,2021CFB556)
绿色化工过程教育部重点实验室开放基金项目(No.GCP20200201)
催化材料制备及应用湖北省重点实验室开放基金项目(No.202023504)
新型反应器与绿色化学工艺湖北省重点实验室(武汉工程大学)开放基金项目(No.40201002)资助。
关键词
磷酸酯
前药
磷酸酯化
合成方法
phosphoesters
prodrugs
phosphorylation
synthetic methods
