The comparative antimalarial properties of weak base and neutral synthetic ozonides.
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 LogP/D(pH)(7.4) values were tolerated, although more lipophilic ozonides tended to be less metabolically stable.
Tang
Yuanqing
Y
College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA.
Wittlin
Sergio
S
Charman
Susan A
SA
Chollet
Jacques
J
Chiu
Francis C K
FC
Morizzi
Julia
J
Johnson
Lisa M
LM
Tomas
Josefina Santo
JS
Scheurer
Christian
C
Snyder
Chistopher
C
Zhou
Lin
L
Dong
Yuxiang
Y
Charman
William N
WN
Matile
Hugues
H
Urwyler
Heinrich
H
Dorn
Arnulf
A
Vennerstrom
Jonathan L
JL
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects; D051381:Rats
C503429:1,2,4-trioxane; D000962:Antimalarials; D006571:Heterocyclic Compounds