药物分子氘代修饰方法研究进展  

Research Progress of Deuterated Modification of Drug Molecules

作　　者：李嘉怡 王翰丞 张涵 吴星宇 陈秋实 张庆伟[2,3] LI Jianyi;WANG Hancheng;ZHANG Han;WU Xingyu;CHEN Qiushi;ZHANG Qingwei(School of Chemistry&Chemical Engineering,Shanghai University of Engineering Science,Shanghai 201620;Shanghai Institute of Pharmaceutical Industry Co.,Ltd.,China State Institute of Pharmaceutical Industry,Shanghai 201203;National Key Lab.of Lead Druggability Research,Shanghai Institute of Pharmaceutical Industry Co.,Ltd.,Shanghai 201203)

机构地区：[1]上海工程技术大学化学化工学院,上海201620 [2]中国医药工业研究总院上海医药工业研究院有限公司,上海201203 [3]上海医药工业研究院有限公司,先导物成药性研究全国重点实验室,上海201203

出　　处：《中国医药工业杂志》2024年第11期1449-1466,共18页Chinese Journal of Pharmaceuticals

基　　金：上海市“科技创新行动计划”项目(21S11908000)。

摘　　要：氘代修饰是通过将药物分子中特定氢原子(H)替换成氘原子(D),从而改善药物分子在体内吸收、分布、代谢的效果,降低给药剂量或频率,提高安全性并获得更佳疗效的方法。氘代修饰已经成为理性药物设计和成药性优化的重要策略。氘代修饰方法主要包括化学合成法和生物酶催化法。其中,化学合成法包括含氘中间体引入法、卤素或不饱和键还原法、酸碱催化及金属催化的氢氘交换法等;生物酶催化法包括生物酶催化的氢氘交换、还原氘代和脱羧氘代法等。文章归纳了氘代修饰方法的最新研究进展,以期为氘代药物的研发提供一定参考。Deuterium substitution is a method that involves replacing specific hydrogen(H)atoms in drug molecules with deuterium(D)atoms,thereby improving the absorption,distribution,metabolism,and affecting of the drug molecules within the body.It can reduce the dosage or frequency of administration,enhance safety,and achieve better therapeutic outcomes.Nowadays,deuterium substitution has become an important strategy in rational drug design and optimization of druggability.The methods of deuterated modification primarily include chemical synthesis and enzymatic catalysis.Chemical synthesis encompasses techniques such as the introduction of deuterated intermediates,halogen or unsaturated bond reduction,acid/base catalysis,and metal-catalyzed hydrogen-deuterium exchange.Enzymatic catalysis involves methods such as enzyme-catalyzed hydrogen-deuterium exchange,reductive deuteration,and decarboxylative deuteration.This review outlines the latest research progress of drug molecule deuteration in recent years with the aim of providing references for the research and development of deuterated drugs.

关 键 词：药物分子 氘代修饰 合成方法 研究进展 

分 类 号：TQ460.6[化学工程—制药化工] R914.2[医药卫生—药物化学]