A series of novel 7-aryl-7-deazaadenine-based N-branched acyclic nucleoside phosphonates (aza-ANPs) has been prepared using the optimized Suzuki cross-coupling reaction as the key synthetic step. The final free phosphonates 15a-h were inactive, due to their inefficient transport across cell membranes, but they inhibited Trypanosoma brucei adenine phosphoribosyltransferase (TbrAPRT1) with K_i values of 1.7–14.1 μM. The corresponding phosphonodiamidate prodrugs 14a-h exhibited anti-trypanosomal activity in the Trypanosoma brucei brucei cell-based assay with EC₅₀ values in the range of 0.58–6.8 μM. 7-(4-Methoxy)phenyl-7-deazapurine derivative 14h, containing two phosphonate moieties, was the most potent anti-trypanosomal agent from the series, with EC₅₀ = 0.58 μM and SI = 16. Finally, phosphonodiamidate prodrugs 14a-h exerted low micromolar cytotoxicity against leukemia and/or cancer cell lines tested.

以优化的 Suzuki 交叉偶联反应为关键合成步骤，制备了一系列新型 7-aryl-7-deazaadenine 基N支链无环核苷膦酸酯 (aza-ANPs)。最终的游离膦酸盐15a-h没有活性，因为它们在细胞膜上的转运效率低下，但它们抑制了布氏锥虫腺嘌呤磷酸核糖基转移酶 ( Tbr APRT1)，K _i值为 1.7–14.1 μM。相应的膦酰二酰胺前药14a-h在具有 EC _50的基于布氏锥虫细胞的测定中表现出抗锥虫活性值在 0.58–6.8 μM 范围内。7-(4-Methoxy)phenyl-7-deazapurine 衍生物14h含有两个膦酸盐部分，是该系列中最有效的抗锥虫药物，EC ₅₀  = 0.58 μM 和 SI = 16。最后，膦酰二胺前药14a-h对测试的白血病和/或癌细胞系表现出低微摩尔细胞毒性。