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

Bioorg Med Chem Lett. 2007 Mar 1;17(5):1260-5. doi: 10.1016/j.bmcl.2006.12.007. Epub 2006 Dec 15.

Authors

Yuanqing Tang¹, 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

Affiliation

¹ College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA.

PMID: 17189686
DOI: 10.1016/j.bmcl.2006.12.007

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antimalarials / chemical synthesis*
Antimalarials / pharmacology
Crystallography, X-Ray
Heterocyclic Compounds / chemical synthesis*
Heterocyclic Compounds / chemistry
Molecular Structure
Structure-Activity Relationship

Substances

1,2,4-trioxane
Antimalarials
Heterocyclic Compounds