Weak Base Dispiro-1,2,4-Trioxolanes: Potent Antimalarial Ozonides

Authors

Yuanqing Tang, College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA
Yuxiang Dong, College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA
Sergio Wittlin, Swiss Tropical Institute, Socinstrasse 57, CH-4002 Basel, Switzerland
Susan A. Charman, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Vic. 3052, Australia
Jacques Chollet, Swiss Tropical Institute, Socinstrasse 57, CH-4002 Basel, Switzerland
Francis C. K. Chiu, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Vic. 3052, Australia
William N. Charman, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Vic. 3052, Australia
Hugues Matile, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, CH-4070 Basel, Switzerland
Heinrich Urwyler, Basilea Pharmaceutica Ltd., Grenzacherstrasse 487, CH-4058 Basel, Switzerland
Arnulf Dorn, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, CH-4070 Basel, Switzerland
Saroj Bajpai, College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA
Xiaofang Wang, College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA
Maniyan Padmanilayam, College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA
Jean M. Karle, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, DC, USA
Reto Brun, Swiss Tropical Institute, Socinstrasse 57, CH-4002 Basel, Switzerland
Jonathan L. Vennerstrom, College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA

Document Type

Article

Date of this Version

2007

Comments

Published in Bioorganic & Medicinal Chemistry Letters 17 (2007) 1260–1265.

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.