Chapter Fourteen - A Decade of Deuteration in Medicinal Chemistry

Abstract The use of deuterium substitution in an effort to produce kinetic isotope effects (KIEs) that favorably alter pharmacokinetics and metabolism in drug discovery has accelerated in the last decade. While the effects of deuteration remain highly experimentally determined and are unpredictable, an increasing number of deuterated drug candidates have progressed from early patent filings to successful proof-of-concept human studies, including the first FDA-approved deuterated drug. The scope of use of KIEs in drug design has expanded, and now deuteration of drug candidates and tool compounds, including imaging ligands, has become a welcome instrument in the arsenal of medicinal chemists. It is expected that experimentation with strategic introduction of deuterium into the structures of organic compounds will continue to increase and may enable the future development of a variety of novel drugs and chemical tools. In this chapter an update on the topic of deuterium substitution in medicinal chemistry will be provided, focusing on the diversity of ways in which medicinal chemists are using deuteration in their efforts to deliver better drugs.