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摘要
许多药物具有不良的吸收、分布、代谢和排泄(ADME)特性,这阻止了它们的广泛使用或限制了它们在某些适应症中的使用。除了制备技术和前药策略外,氘修饰是改善ADME性能的可行方法。近年来,氘化药物越来越受到制药行业的关注。到目前为止,FDA已经批准了两种氘化药物。2017年,austedo被FDA批准为美国亨廷顿病新药,这是第一个在全球上市的氘药物。近日(2021年6月9日),多纳非尼在中国上市;这一结果引起了各大制药公司和制药行业对氘技术的重新重视。此外,BMS-986165、RT001、ALK-001、HC-1119、AVP-786等药物正在进行III期临床研究,部分固体氘化合物已进入I、II期临床试验。氘策略在药学研究中得到了广泛的应用,成为近年来药学研究的热点。本文综述了氘化药物的研究与发展,重点介绍了氘修饰对药物的影响、氘策略的优点以及氘化药物的合成策略。希望为临床应用、新的氘化学实体的发现和新型氘化药物的研发提供参考。
关键词: 氘化药物,单胺氧化酶,毒性,药物代谢,药物合成,ADME性质。
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