Total Syntheses of Deuterated Drugs: A Comprehensive Review

Top Curr Chem (Cham). 2025 Aug 21;383(3):31. doi: 10.1007/s41061-025-00515-x.

Abstract

Deuterium is a safe bioisostere of hydrogen, and its selective labeling has a great prominence in medicinal chemistry for the amelioration of the pharmacokinetic profiles of the drugs. The deuterium-labeled pharmaceutically active compounds have been observed to exhibit broad applications, either as deuterated drugs or as pharmacokinetic probes (biomarkers). The deuterated drugs offer improved bioactivity and metabolic profile in terms of tolerability, efficacy, and reduced toxicity. In this manuscript, the synthetic strategies of various deuterated drugs including antiviral, anticancer, antiarrhythmic, antidiabetic, anticholinergic, antibiotics, antidepressants, and antipyretics have been documented. In addition, this review article also comprises a broad class of miscellaneous drugs i.e., antiasthmatic drugs, antiseptics, topical analgesics, antifibrotic agents, immunosuppressants, and central nervous system (CNS) suppressants. Additionally, the synthesis of several deuterated pharmaceutically active compounds as biomarkers has also been compiled in this review. Leveraging the modern platform of precision deuteration, this review article provides a repertoire of synthetic strategies for the synthesis of several deuterated drugs reported over a period of 2005-2024 (two decades).

Keywords: Biomarkers; Deuterated drugs; Precision deuteration.

Publication types

  • Review

MeSH terms

  • Deuterium* / chemistry
  • Humans
  • Pharmaceutical Preparations / chemical synthesis
  • Pharmaceutical Preparations / chemistry

Substances

  • Deuterium
  • Pharmaceutical Preparations