title: Synthesis of novel 2-alkoxy-3-amino-3-arylpropan-1-ols and 5-alkoxy-4-aryl-1,3-oxazinanes with antimalarial activity.
abstract: 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.
authors.affiliation: Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, B-9000 Ghent, Belgium.
authors.forename: Matthias
authors.initials: M
authors.lastname: D'hooghe
authors.forename: Stijn
authors.initials: S
authors.lastname: Dekeukeleire
authors.forename: Karen
authors.initials: K
authors.lastname: Mollet
authors.forename: Carmen
authors.initials: C
authors.lastname: Lategan
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Smith
authors.forename: Kelly
authors.initials: K
authors.lastname: Chibale
authors.forename: Norbert
authors.initials: N
authors.lastname: De Kimpe
mesh_terms: 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
chemical_list: D000605:Amino Alcohols; D000962:Antimalarials; D010078:Oxazines; D020005:Propanols