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

doi:10.1016/j.bmcl.2006.08.046

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

Pharmaceutical Science

Research output: Contribution to journal › Article › peer-review

60 Scopus citations

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 language	English (US)
Pages (from-to)	5542-5545
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2006.08.046
State	Published - Nov 1 2006

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

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10.1016/j.bmcl.2006.08.046

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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

Padmanilayam, M, Scorneaux, B, Dong, Y, Chollet, J, Matile, H, Charman, SA, Creek, DJ, Charman, WN, Tomas, JS, Scheurer, C, Wittlin, S, Brun, R & Vennerstrom, JL 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, vol. 16, no. 21, pp. 5542-5545. https://doi.org/10.1016/j.bmcl.2006.08.046

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

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.",

keywords = "1,2,4-Trioxolane, Antimalarial, Artemisinin, Secondary ozonide",

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

note = "Funding Information: This investigation received financial support from the UNDP/WORLD BANK/WHO Special Programme for Research and Training in Tropical Diseases (TDR ID No. 960275) and Medicines for Malaria Venture (MMV).",

year = "2006",

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doi = "10.1016/j.bmcl.2006.08.046",

language = "English (US)",

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pages = "5542--5545",

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AU - Padmanilayam, Maniyan

AU - Scorneaux, Bernard

AU - Dong, Yuxiang

AU - Chollet, Jacques

AU - Matile, Hugues

AU - Charman, Susan A.

AU - Creek, Darren J.

AU - Charman, William N.

AU - Tomas, Josefina Santo

AU - Scheurer, Christian

AU - Wittlin, Sergio

AU - Brun, Reto

AU - Vennerstrom, Jonathan L.

N1 - Funding Information: This investigation received financial support from the UNDP/WORLD BANK/WHO Special Programme for Research and Training in Tropical Diseases (TDR ID No. 960275) and Medicines for Malaria Venture (MMV).

PY - 2006/11/1

Y1 - 2006/11/1

N2 - 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.

AB - 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.

KW - 1,2,4-Trioxolane

KW - Antimalarial

KW - Artemisinin

KW - Secondary ozonide

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

Abstract

Keywords

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