Fluoroartemisinins: metabolically more stable antimalarial artemisinin derivatives.
This report is an overview on the design, preparation, and evaluation of metabolically stable artemisinins, using fluorine substitution. The chemical challenges encountered for the incorporation of fluorine-containing elements and the preparation of a large range of 10-trifluoromethyl artemisinin derivatives are detailed. Impact of the fluorine substitution on the antimalarial activity is also highlighted. Preclinical data of lead compounds, and evidence for their strong and prolonged antimalarial activity are presented.
Bégué
Jean-Pierre
JP
BIOCIS-UMR-CNRS-8086, Faculté de Pharmacie, 2 Rue J.B. Clément, Chatenay-Malabry, 92296, France.
Bonnet-Delpon
Danièle
D
D000818:Animals; D000962:Antimalarials / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D037621:Artemisinins / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D004987:Ethers; D005461:Fluorine / Q000737:chemistry*; D006207:Half-Life; D051379:Mice; D010962:Plasmodium berghei / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D051381:Rats
D000962:Antimalarials; D037621:Artemisinins; D004987:Ethers; D005461:Fluorine