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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Clinical Application and Synthesis Methods of Deuterated Drugs

Author(s): Xiao-Liang Xu, Wen Zhang and Guo-Wu Rao*

Volume 30, Issue 36, 2023

Published on: 12 January, 2023

Page: [4096 - 4129] Pages: 34

DOI: 10.2174/0929867330666221122123201

Price: $65


Many drugs have adverse absorption, distribution, metabolism, and excretory (ADME) properties that prevent their widespread use or limit their use in some indications. In addition to preparation techniques and prodrug strategies, deuterium modification is a viable method for improving ADME properties. Deuterated drugs have attracted increasing attention from the pharmaceutical industry in recent years. To date, two deuterated drugs have been approved by the FDA. In 2017, austedo was approved by the FDA as a new drug for Huntington's disease in the United States, the first deuterium drug to be marketed worldwide. Recently (June 9, 2021), donafinil has been listed in China; this result has caused major pharmaceutical companies and the pharmaceutical industry to pay attention to deuterium technology again. In addition, BMS-986165, RT001, ALK-001, HC-1119, AVP-786 and other drugs are in phase III clinical studies, and some solid deuterium compounds have entered phase I and II clinical trials. The deuterium strategy has been widely used in pharmaceutical research and has become a hot spot in pharmaceutical research in recent years. In this paper, the research and development of deuterated drugs are reviewed, and the influence of deuterium modification on drugs, the advantages of deuterium strategies and the synthesis strategies of deuterated drugs are mainly introduced. Hoping to provide references for clinical application, the discovery of new deuterium chemical entities and research and development of new deuterated drugs.

Keywords: Deuterated drugs, mono-amine oxidase, toxicity, drug metabolism, drug synthesis, ADME properties.

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