Fluorinated mechanism-based inhibitors: common themes and recent developments.
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.
Christina
C
Tysoe
Department of Chemistry, University of British Columbia, 2036, Main Mall, Vancouver, British Columbia, V6T 1Z1, Canada. withers@chem.ubc.ca.
Stephen G
SG
Withers
D002626:Chemistry, Pharmaceutical; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004798:Enzymes / Q000737:chemistry*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D004798:Enzymes; D006845:Hydrocarbons, Fluorinated