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.
Current Topics in Medicinal Chemistry
Title:Fluorinated Mechanism-Based Inhibitors: Common Themes and Recent Developments
Volume: 14 Issue: 7
Author(s): Christina Tysoe and Stephen G. Withers
Affiliation:
Keywords: Amine oxidases, drug design, enzyme inhibition, enzyme mechanisms, fluorine, glycosidases, mechanism-based inhibition.
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.
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Cite this article as:
Tysoe Christina and Withers G. Stephen, Fluorinated Mechanism-Based Inhibitors: Common Themes and Recent Developments, Current Topics in Medicinal Chemistry 2014; 14 (7) . https://dx.doi.org/10.2174/1568026614666140202204602
DOI https://dx.doi.org/10.2174/1568026614666140202204602 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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