Antimalarial activity of N-alkyl amine, carboxamide, sulfonamide, and urea derivatives of a dispiro-1,2,4-trioxolane piperidine

Maniyan Padmanilayam, Bernard Scorneaux, Yuxiang Dong, Jacques Chollet, Hugues Matile, Susan A. Charman, Darren J. Creek, William N. Charman, Josefina Santo Tomas, Christian Scheurer, Sergio Wittlin, Reto Brun, Jonathan L. Vennerstrom

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Abstract

With an aim to identify a dispiro-1,2,4-trioxolane with high oral activity and good physicochemical properties, 27 derivatives of an achiral piperidine trioxolane were synthesized; most were potent antimalarial peroxides with IC50s ranging from 0.20 to 7.0 ng/mL. The oral efficacies of two of these were superior to artesunate and comparable to artemether. The attractive chemical simplicity of these compounds is balanced only by an apparent metabolic susceptibility.

Original languageEnglish (US)
Pages (from-to)5542-5545
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume16
Issue number21
DOIs
StatePublished - Nov 1 2006

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Keywords

  • 1,2,4-Trioxolane
  • Antimalarial
  • Artemisinin
  • Secondary ozonide

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Padmanilayam, M., Scorneaux, B., Dong, Y., Chollet, J., Matile, H., Charman, S. A., Creek, D. J., Charman, W. N., Tomas, J. S., Scheurer, C., Wittlin, S., Brun, R., & Vennerstrom, J. L. (2006). Antimalarial activity of N-alkyl amine, carboxamide, sulfonamide, and urea derivatives of a dispiro-1,2,4-trioxolane piperidine. Bioorganic and Medicinal Chemistry Letters, 16(21), 5542-5545. https://doi.org/10.1016/j.bmcl.2006.08.046