Institut für Pharmazeutische und Medizinische Chemie der Westfälischen Wilhelms-Universität Münster , Corrensstraße 48, D-48149 Münster, Germany.
J Med Chem. 2013 Sep 26;56(18):7442-8. doi: 10.1021/jm401007p. Epub 2013 Sep 9.
Various natural products with the chromane and chromene scaffold exhibit high antiprotozoal activity. The natural product encecalin (7) served as key intermediate for the synthesis of different ethers 9, amides 11, and amines 12. The chromane analogues 14 and the phenols 15 were obtained by reductive amination of ketones 13 and 6, respectively. Angelate 3, ethers 9, and amides 11 did not show considerable antiprotozoal activity. However, the chromene and chromane derived amines 12, 14, and 15 revealed promising antiprotozoal activity and represent novel lead compounds. Whereas benzylamine 12a and α-methylbenzylamine 12g were active against P. falciparum with IC50 values in the range of chloroquine, the analogous phenols 15a and 15b were unexpectedly 10- to 25-fold more potent than chloroquine with selectivity indexes of 6760 and 1818, respectively. The phenylbutylamine 14d based on the chromane scaffold has promising activity against T. brucei rhodesiense and L. donovani.
多种具有色烯和色烯骨架的天然产物表现出很强的抗原生动物活性。天然产物恩西卡林（7）是合成不同醚 9、酰胺 11 和胺 12 的关键中间体。色烯类似物 14 和酚 15 是通过酮 13 和 6 的还原胺化得到的。香叶酯 3、醚 9 和酰胺 11 没有表现出显著的抗原生动物活性。然而，色烯和色烯衍生的胺 12、14 和 15 显示出有希望的抗原生动物活性，代表了新型的先导化合物。苄胺 12a 和α-甲基苄胺 12g 对疟原虫具有活性，IC50 值与氯喹相当，而类似的酚 15a 和 15b 出人意料地比氯喹强 10 到 25 倍，选择性指数分别为 6760 和 1818。基于色烯骨架的苯基丁基胺 14d 对布氏锥虫和利什曼原虫具有很好的活性。
