Clinical Application and Synthesis Methods of Deuterated Drugs

Abstract

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 Ⅱclinical 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.

A Mini Review on Liquid Phase Catalytic Exchange for Hydrogen Isotope Separation: Current Status and Future Potential

“…For example, deuterated water (D2O) is commonly used as a solvent in NMR spectroscopy to study the structure of organic molecules. Deuterated compounds also have applications in the pharmaceutical industry, where they are used to study metabolic processes and the stability of drugs [6,7]. Another example is deuterated benzene, used as a solvent in certain NMR experiments [8].…”