| Institution: | 1. College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA;2. Swiss Tropical Institute, Socinstrasse 57, CH-4002 Basel, Switzerland;3. Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia;4. F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, CH-4070 Basel, Switzerland;5. Basilea Pharmaceutica Ltd, Grenzacherstrasse 487, CH-4058 Basel, Switzerland |
| Abstract: | Thirty-three N-acyl 1,2,4-dispiro trioxolanes (secondary ozonides) were synthesized. For these ozonides, weak base functional groups were not required for high antimalarial potency against Plasmodium falciparum in vitro, but were necessary for high antimalarial efficacy in Plasmodium berghei-infected mice. A wide range of Log P/DpH 7.4 values were tolerated, although more lipophilic ozonides tended to be less metabolically stable. |
