Weak base dispiro-1,2,4-trioxolanes: potent antimalarial ozonides.
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.
Tang
Yuanqing
Y
College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE, USA.
Dong
Yuxiang
Y
Wittlin
Sergio
S
Charman
Susan A
SA
Chollet
Jacques
J
Chiu
Francis C K
FC
Charman
William N
WN
Matile
Hugues
H
Urwyler
Heinrich
H
Dorn
Arnulf
A
Bajpai
Saroj
S
Wang
Xiaofang
X
Padmanilayam
Maniyan
M
Karle
Jean M
JM
Brun
Reto
R
Vennerstrom
Jonathan L
JL
D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013329:Structure-Activity Relationship
C503429:1,2,4-trioxane; D000962:Antimalarials; D006571:Heterocyclic Compounds