Design, synthesis, derivatization, and structure-activity relationships of simplified, tricyclic, 1,2,4-trioxane alcohol analogues of the antimalarial artemisinin.

Journal of Medicinal Chemistry
J N CummingG H Posner

Abstract

Novel C4-(hydroxyalkyl)trioxanes 5d and 5e were designed and synthesized based on an understanding of the molecular mechanism of action of similar 1,2,4-trioxanes structurally related to the antimalarial natural product artemisinin (1). In vitro efficacies of these two new pairs of C4-diastereomers against chloroquine-sensitive Plasmodium falciparum support conclusions about the importance to antimalarial activity of formation of a C4 radical by a 1,5-hydrogen atom abstraction. Derivatives 6, 7, and 21 of C4 beta-substituted trioxane alcohols 4a, 5d, and 5e were prepared, each in a single-step, high-yielding transformation. Four of these new analogues, 6a-c and 7, are potent in vitro antimalarials, having 140 to 50% of the efficacy of the natural trioxane artemisinin (1).

References

Dec 1, 1979·Antimicrobial Agents and Chemotherapy·R E DesjardinsJ D Chulay
Jun 26, 1992·Journal of Medicinal Chemistry·A M PetrosS W Fesik
Apr 1, 1995·The Pediatric Infectious Disease Journal·R W Steele, B Baffoe-Bonnie
Jan 1, 1995·Annual Review of Entomology·F H Collins, S M Paskewitz
Jan 1, 1994·Transactions of the Royal Society of Tropical Medicine and Hygiene·G C Cook
Apr 1, 1994·The American Journal of Tropical Medicine and Hygiene·G H PosnerR N Rossan
Jul 11, 1996·The New England Journal of Medicine·S L Hoffman
Jun 1, 1996·Microbiological Reviews·S R MeshnickS Kamchonwongpaisan
Jan 1, 1997·Journal of Chemical Information and Computer Sciences·M GrigorovD Maric
Dec 20, 1996·Molecular and Biochemical Parasitology·P J Rosenthal, S R Meshnick
Apr 1, 1997·The American Journal of Tropical Medicine and Hygiene·J M PetrasT G Brewer

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Citations

Apr 5, 2001·Trends in Parasitology·P L OlliaroY Yuthavong
May 30, 2001·Trends in Parasitology·G P Posner, S R Meshnick
Dec 15, 2004·Natural Product Research·Dharmarajan SriramPerumal Yogeeswari
May 17, 2001·Antimicrobial Agents and Chemotherapy·L K BascoB Meunier
Jan 18, 2006·Journal of Pharmaceutical and Biomedical Analysis·C DebnathA Michelitsch
Oct 30, 2010·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Geoffrey D Brown
Apr 29, 2005·Organic & Biomolecular Chemistry·Fadia NajjarHenri Vial
Feb 6, 2002·Chembiochem : a European Journal of Chemical Biology·O Dechy-CabaretB Meunier
May 18, 2000·The Journal of Organic Chemistry·H J Hamann, J Liebscher
Nov 26, 2002·Journal of Natural Products·Ji-Xun ZhanDe-An Guo
Aug 24, 2010·Journal of Chemical Information and Modeling·Amit K GuptaAnil K Saxena
Nov 4, 2005·Bioorganic & Medicinal Chemistry·Alex Gutterres TarantoMartha Teixeira de Araujo
Apr 6, 2005·Journal of Chemical Information and Modeling·Marjan A RafieeHossein Naderi-manesh
May 28, 2004·Journal of Medicinal Chemistry·Paul M O'Neill, Gary H Posner
Feb 22, 2002·The Journal of Organic Chemistry·Jérôme CazellesBernard Meunier
Apr 23, 2005·Organic Letters·Christine M DiblasiDerek S Tan

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