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Fluorinated Mechanism-Based Inhibitors: Common Themes and Recent Developments

TitleFluorinated Mechanism-Based Inhibitors: Common Themes and Recent Developments
Publication TypeJournal Article
Year of Publication2014
AuthorsTysoe, C, Withers, SG
JournalCURRENT TOPICS IN MEDICINAL CHEMISTRY
Volume14
Pagination865-874
Date PublishedAPR
ISSN1568-0266
Abstract

Mechanism-based inhibitors are relatively chemically inert compounds that become activated when processed by their target enzyme, leading to covalent enzyme inactivation. Fluorine substitution confers a number of properties that are beneficial to the chemistry of such inhibitors and to their potential use as pharmaceuticals, and indeed several fluorinated mechanism-based inhibitors have made it to clinical usage over the past 50 years. Well-known examples are the 5-fluorouracil metabolite, 5-fluoro-2'-deoxyuridine-5'-monophosphate, which is used in the treatment of cancer, and alpha-difluoromethylornithine for the treatment of African sleeping sickness. As the prevalence of fluorine in medicinal chemistry continues to rise, more and more medically relevant fluorinated mechanism-based inhibitors are being developed with a variety of interesting properties and uses.