Deuterium protium substituens: стратегия создания новых лекарственных препаратов: ФАРМАЦЕВТИЧЕСКАЯ ХИМИЯ, ФАРМАКОГНОЗИЯ

Екатерина Александровна Попова

Deuterium protium substituens: a strategy for the development of new drugs

PHARMACEUTICAL CHEMISTRY, PHARMACOGNOSY

Ekaterina A. Popova Saint Petersburg State Pediatric Medical University https://orcid.org/0000-0001-5868-6437

Keywords:

дейтерированные лекарственные препараты медицинская химия кинетический изотопный эффект деутетрабеназин деукравацитиниб deuterated drugs medicinal chemistry kinetic isotope effect deutetrabenazine deucravacitinib

Abstract

This micro-review presents a modern approach to drug development based on the isotopic substitution of protium with deuterium in biologically active molecules. The theoretical background of the method, including the phenomenon of the primary kinetic isotope effect underlying changes in metabolic stability, is discussed. Using two key drugs, deutetrabenazine and deucravacitinib, the review illustrates two strategies: improving the pharmacokinetic and toxicological profiles of an existing protium analogue and designing a novel drug de novo that initially contains a deuterated moiety. The main limitations of the method, including synthetic challenges, unpredictability of primary kinetic isotope effect, and the risk of metabolic switching, are highlighted. A separate section is devoted to the current state of research on deuterated drugs in the Russian Federation

Author Biography

Ekaterina A. Popova, Saint Petersburg State Pediatric Medical University

Cand. Sci. (Chemistry), Associate Professor, Associate Professor, Dept. of General and Medical Chemistry named after prof. V.V. Khorunzhy

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