Synthesis of novel 2-alkoxy-3-amino-3-arylpropan-1-ols and 5-alkoxy-4-aryl-1,3-oxazinanes with antimalarial activity.
A variety of novel syn-2-alkoxy-3-amino-3-arylpropan-1-ols was prepared through LiAlH(4)-promoted reductive ring-opening of cis-3-alkoxy-4-aryl-beta-lactams in Et(2)O. The latter gamma-aminoalcohols were easily converted into cis-5-alkoxy-4-aryl-1,3-oxazinanes using formaldehyde in THF. Both series of compounds were evaluated against a chloroquine sensitive strain of Plasmodium falciparum (D10), revealing micromolar potency for almost all representatives. Eleven compounds exhibited antimalarial activity with IC(50) values of <or=30 microM, and the majority of these compounds did not show cytotoxicity at the concentrations tested.
D'hooghe
Matthias
M
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, B-9000 Ghent, Belgium.
Dekeukeleire
Stijn
S
Mollet
Karen
K
Lategan
Carmen
C
Smith
Peter J
PJ
Chibale
Kelly
K
De Kimpe
Norbert
N
D000605:Amino Alcohols / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D010078:Oxazines / Q000138:chemical synthesis* / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects; D020005:Propanols; D013329:Structure-Activity Relationship
D000605:Amino Alcohols; D000962:Antimalarials; D010078:Oxazines; D020005:Propanols