D'hooghe Matthias, Dekeukeleire Stijn, Mollet Karen, Lategan Carmen, Smith Peter J, Chibale Kelly, De Kimpe Norbert
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, B-9000 Ghent, Belgium.
J Med Chem. 2009 Jul 9;52(13):4058-62. doi: 10.1021/jm9002632.
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.
通过在乙醚中用氢化铝锂促进顺式-3-烷氧基-4-芳基-β-内酰胺的还原开环反应，制备了多种新型的syn-2-烷氧基-3-氨基-3-芳基丙醇。使用四氢呋喃中的甲醛，可将后者的γ-氨基醇轻松转化为顺式-5-烷氧基-4-芳基-1,3-恶嗪烷。对这两类化合物针对氯喹敏感的恶性疟原虫菌株（D10）进行了评估，结果显示几乎所有代表物都具有微摩尔级别的效力。11种化合物表现出抗疟活性，其半数抑制浓度（IC50）值≤30微摩尔，并且这些化合物中的大多数在测试浓度下未显示出细胞毒性。
