Synthesis of Novel 2-Alkoxy-3-amino-3-arylpropan-1-ols and 5-Alkoxy-4-aryl-1,3-oxazinanes with Antimalarial Activity

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• 作者：Matthias D’ ; hooghe ; Stijn Dekeukeleire ; Karen Mollet ; Carmen Lategan ; Peter J. Smith ; Kelly Chibale ; Norbert De Kimpe
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：July 9, 2009
• 年：2009
• 卷：52
• 期：13
• 页码：4058-4062
• 全文大小：105K
• 年卷期：v.52,no.13(July 9, 2009)
• ISSN：1520-4804

文摘

A variety of novel syn-2-alkoxy-3-amino-3-arylpropan-1-ols was prepared through LiAlH₄-promoted reductive ring-opening of cis-3-alkoxy-4-aryl-β-lactams in Et₂O. The latter γ-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 IC₅₀ values of ≤30 μM, and the majority of these compounds did not show cytotoxicity at the concentrations tested.