A series of N-benzylated phosphoramidate esters, containing a 3,4-dihydroxyphenyl Mg²⁺-chelating group, has been synthesised in five steps as analogues of fosmidomycin, a Plasmodium falciparum 1-deoxy-1-d-xylulose-5-phosphate reductoisomerase (PfDXR) inhibitor. The 3,4-dihydroxyphenyl group effectively replaces the Mg²⁺-chelating hydroxamic acid group in fosmidomycin. The compounds showed very encouraging anti-parasitic activity with IC₅₀ values of 5.6–16.4 µM against Plasmodium falciparum parasites and IC₅₀ values of 5.2 – 10.2 µM against Trypanosoma brucei brucei (T.b.brucei). Data obtained from in silico docking of the ligands in the PfDXR receptor cavity (3AU9)⁵ support their potential as PfDXR inhibitors.

已通过五个步骤合成了一系列含有3,4-二羟基苯基Mg ²⁺螯合基团的N-苄基氨基磷酸酯类，作为膦酰胺（恶性疟原虫1-deoxy-1- d -xylulose-5-phosphate）的类似物还原异构酶（Pf DXR）抑制剂。3，4-二羟基苯基基团有效地替代了磷霉素中的Mg ²⁺螯合异羟肟酸基团。这些化合物显示出令人鼓舞的抗寄生虫活性，对恶性疟原虫的IC ₅₀值为5.6–16.4 µM，对布鲁氏锥虫（Tbbrucei）的IC ₅₀值为5.2 – 10.2 µM。。从配体在Pf DXR受体腔（3AU9）⁵中的计算机对接获得的数据支持它们作为PfDXR抑制剂的潜力。