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.