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Fluorinated Mechanism-Based Inhibitors: Common Themes and Recent Developments

[ Vol. 14 , Issue. 7 ]


Christina Tysoe and Stephen G. Withers   Pages 865 - 874 ( 10 )


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 α - 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.


Amine oxidases, drug design, enzyme inhibition, enzyme mechanisms, fluorine, glycosidases, mechanism-based inhibition.


Department of Chemistry, University of British Columbia, 2036, Main Mall, Vancouver, British Columbia, V6T 1Z1, Canada.

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