Equipe "Biomolécules Fluorées", Chimie Organique Bioorganique Réactivité et Analyses (COBRA), Institut de Recherche en Chimie Organique Fine de Rouen (IRCOF), UMR CNRS 6014, Université et Institut National des Sciences Appliquées (INSA) de Rouen, F-76821 Mont Saint Aignan Cedex, France.
Bioorg Med Chem Lett. 2013 Nov 15;23(22):6167-71. doi: 10.1016/j.bmcl.2013.08.108. Epub 2013 Sep 7.
In this Letter we report on a multi-step synthesis of 5-((arylthio- and heteroarylthio)-methylene)-3-(2,2,2-trifluoroethyl)furan-2(5H)-ones starting from γ-keto thiolester or γ-keto carboxylic acid. The key intermediate γ-lactones were then reacted with 4-aminoquinoline-derived amines via ring opening-ring closure (RORC) process affording the corresponding γ-hydroxy-γ-lactams in moderate to good yields. In vitro antimalarial activity of the resulting new 4-aminoquinoline γ-lactams were evaluated against Plasmodium falciparum clones of variable sensitivity (3D7 and W2) and were found to be active in the range of 89-1600 nM with good resistance index and did not show cytotoxicity in vitro when tested against human umbilical vein endothelial cells (HUVEC) up to concentration of 50 μM.
在这封信件中，我们报告了一种多步合成 5-((芳基硫代和杂芳基硫代)-亚甲基)-3-(2,2,2-三氟乙基)呋喃-2(5H)-酮的方法，该方法从γ-酮硫醇酯或γ-酮羧酸开始。然后，关键中间体γ-内酯通过开环-闭环（RORC）反应与 4-氨基喹啉衍生的胺反应，以中等至良好的收率得到相应的γ-羟基-γ-内酰胺。对所得的新型 4-氨基喹啉γ-内酰胺进行了体外抗疟活性评估，针对不同敏感性的疟原虫克隆（3D7 和 W2）进行了评估，其活性范围为 89-1600 nM，耐药指数良好，在 50 μM 浓度下对人脐静脉内皮细胞（HUVEC）进行体外测试时没有细胞毒性。
