4.7 Article

Deuterated driven new chemical entities: An optimistic way to improve therapeutic efficacy

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BIOORGANIC CHEMISTRY
卷 135, 期 -, 页码 -

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ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2023.106490

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Deuterated drugs; Pharmacokinetics; Antimicrobial resistance; Chemical stability; Nonradioactive isotope

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In organic chemistry, the use of deuterium exchange as a tool to study chemical reaction mechanisms is well explored. Recently, there has been growing interest in investigating the therapeutic potential of deuterated bioactive molecules. The review provides a conceptual framework on the importance of deuterium atom in drug chemical structure and its biological value in improved physiochemical properties, pharmacokinetics, and toxicity. It also updates recent deuteration methods, challenges in drug development, and deuterium-based imaging in diagnosis.
In organic chemistry, the use of deuterium exchange as a tool to study the mechanism of chemical reaction has been well explored. Since two decades, the research focus on deuterated bioactive molecules has been gaining attention for investigating the therapeutic potential of deuterium replacement in a chemical structure. Recently, Food Drug Administration (FDA) approved the first deuterium-labeled drug deutetrabenazine, and notified the deuterated drugs as new chemical entities (NCEs). Henceforth, the deuterium substitution driven structure ac-tivity relationship, preclinical pharmacokinetics, and toxicity studies were much initiated. Deuteration of a bioactive molecule often results in improved therapeutic efficacy due to the altered pharmacokinetic profile. This review provides a conceptual framework on the importance of deuterium atom in chemical structure of a drug, and its biological value in improved physiochemical properties, pharmacokinetics, biological target interaction, diagnosis, and toxicity. In addition, this review concisely updated the recent deuteration methods, chemical stability, challenges in drug development, deuterium-based imaging in diagnosis, and selected synthetic scheme of deuterated molecules.

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