Weak base dispiro-1,2,4-trioxolanes: Potent antimalarial ozonides

Yuanqing Tang; Yuxiang Dong; Sergio Wittlin; Susan A. Charman; Jacques Chollet; Francis C.K. Chiu; William N. Charman; Hugues Matile; Heinrich Urwyler; Arnulf Dorn; Saroj Bajpai; Xiaofang Wang; Maniyan Padmanilayam; Jean M. Karle; Reto Brun; Jonathan L. Vennerstrom

doi:10.1016/j.bmcl.2006.12.007

Weak base dispiro-1,2,4-trioxolanes: Potent antimalarial ozonides

Yuanqing Tang, Yuxiang Dong, Sergio Wittlin, Susan A. Charman, Jacques Chollet, Francis C.K. Chiu, William N. Charman, Hugues Matile, Heinrich Urwyler, Arnulf Dorn, Saroj Bajpai, Xiaofang Wang, Maniyan Padmanilayam, Jean M. Karle, Reto Brun, Jonathan L. Vennerstrom

Pharmaceutical Science

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

63 Scopus citations

Abstract

Thirty weak base 1,2,4-dispiro trioxolanes (secondary ozonides) were synthesized. Amino amide trioxolanes had the best combination of antimalarial and biopharmaceutical properties. Guanidine, aminoxy, and amino acid trioxolanes had poor antimalarial activity. Lipophilic trioxolanes were less stable metabolically than their more polar counterparts.

Original language	English (US)
Pages (from-to)	1260-1265
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2006.12.007
State	Published - Mar 1 2007

Keywords

1,2,4-Trioxolanes
Antimalarial
Artemisinin
Peroxide
Secondary ozonides

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.2006.12.007

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Tang, Y., Dong, Y., Wittlin, S., Charman, S. A., Chollet, J., Chiu, F. C. K., Charman, W. N., Matile, H., Urwyler, H., Dorn, A., Bajpai, S., Wang, X., Padmanilayam, M., Karle, J. M., Brun, R., & Vennerstrom, J. L. (2007). Weak base dispiro-1,2,4-trioxolanes: Potent antimalarial ozonides. Bioorganic and Medicinal Chemistry Letters, 17(5), 1260-1265. https://doi.org/10.1016/j.bmcl.2006.12.007

Tang, Y, Dong, Y, Wittlin, S, Charman, SA, Chollet, J, Chiu, FCK, Charman, WN, Matile, H, Urwyler, H, Dorn, A, Bajpai, S, Wang, X, Padmanilayam, M, Karle, JM, Brun, R & Vennerstrom, JL 2007, 'Weak base dispiro-1,2,4-trioxolanes: Potent antimalarial ozonides', Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 5, pp. 1260-1265. https://doi.org/10.1016/j.bmcl.2006.12.007

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title = "Weak base dispiro-1,2,4-trioxolanes: Potent antimalarial ozonides",

abstract = "Thirty weak base 1,2,4-dispiro trioxolanes (secondary ozonides) were synthesized. Amino amide trioxolanes had the best combination of antimalarial and biopharmaceutical properties. Guanidine, aminoxy, and amino acid trioxolanes had poor antimalarial activity. Lipophilic trioxolanes were less stable metabolically than their more polar counterparts.",

keywords = "1,2,4-Trioxolanes, Antimalarial, Artemisinin, Peroxide, Secondary ozonides",

author = "Yuanqing Tang and Yuxiang Dong and Sergio Wittlin and Charman, {Susan A.} and Jacques Chollet and Chiu, {Francis C.K.} and Charman, {William N.} and Hugues Matile and Heinrich Urwyler and Arnulf Dorn and Saroj Bajpai and Xiaofang Wang and Maniyan Padmanilayam and Karle, {Jean M.} 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). We thank Danielle N. McClennan, Josefina Santo Tomas, Christian Scheurer, and Chistopher Snyder for technical assistance.",

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doi = "10.1016/j.bmcl.2006.12.007",

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T1 - Weak base dispiro-1,2,4-trioxolanes

T2 - Potent antimalarial ozonides

AU - Tang, Yuanqing

AU - Dong, Yuxiang

AU - Wittlin, Sergio

AU - Charman, Susan A.

AU - Chollet, Jacques

AU - Chiu, Francis C.K.

AU - Charman, William N.

AU - Matile, Hugues

AU - Urwyler, Heinrich

AU - Dorn, Arnulf

AU - Bajpai, Saroj

AU - Wang, Xiaofang

AU - Padmanilayam, Maniyan

AU - Karle, Jean M.

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). We thank Danielle N. McClennan, Josefina Santo Tomas, Christian Scheurer, and Chistopher Snyder for technical assistance.

PY - 2007/3/1

Y1 - 2007/3/1

N2 - Thirty weak base 1,2,4-dispiro trioxolanes (secondary ozonides) were synthesized. Amino amide trioxolanes had the best combination of antimalarial and biopharmaceutical properties. Guanidine, aminoxy, and amino acid trioxolanes had poor antimalarial activity. Lipophilic trioxolanes were less stable metabolically than their more polar counterparts.

AB - Thirty weak base 1,2,4-dispiro trioxolanes (secondary ozonides) were synthesized. Amino amide trioxolanes had the best combination of antimalarial and biopharmaceutical properties. Guanidine, aminoxy, and amino acid trioxolanes had poor antimalarial activity. Lipophilic trioxolanes were less stable metabolically than their more polar counterparts.

KW - 1,2,4-Trioxolanes

KW - Antimalarial

KW - Artemisinin

KW - Peroxide

KW - Secondary ozonides

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Weak base dispiro-1,2,4-trioxolanes: Potent antimalarial ozonides

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Keywords

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