Fluorinated Mechanism-Based Inhibitors: Common Themes and Recent Developments

Author(s): Christina Tysoe, Stephen G. Withers

Journal Name: Current Topics in Medicinal Chemistry

Volume 14 , Issue 7 , 2014

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Graphical 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 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.

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

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Article Details

Year: 2014
Published on: 02 February, 2014
Page: [865 - 874]
Pages: 10
DOI: 10.2174/1568026614666140202204602
Price: $65

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