血吸虫病化学治疗的研究——Ⅳ.β-(5-硝基-2-呋喃)丙酰胺类及其α,β-二溴取代衍生物的合成

本文报道38个β-(5-硝基-2-呋喃)丙酰胺及其α,β-二溴取代衍生物的合成。这类化合物的制备是以相应的β-(5-硝基-2-呋喃)丙烯酰胺类化合物(Ⅰ)进行催化氢化或与溴加成而得。经动物筛选发现β-(5-硝基-2-呋喃)丙烯酰胺类的丙烯双键以氢饱和以后生成丙酰胺类化合物(Ⅱ),对感染日本血吸虫病的小白鼠完全失去治疗或预防作用。而以溴饱和双键的α,β-二溴化合物(Ⅲ)则仍然有较显著的杀虫作用。其中尤以β-(5-硝基-2-呋喃)-α,β-二溴丙酰异丙胺(Ⅲ₁₁)和β-(5-硝基-2-呋喃)-α,β-二溴丙酰甘氨酸乙酯(Ⅲ₂₄)最为显著,后者曾试用于临床,证明有一定疗效。

CHEMOTHERAPEUTIC STUDIES ON SCHISTOSOMIASIS——Ⅳ. THE SYNTHESIS OF β-(5-NITRO-2-FURYL)-PROPIONAMIDES AND α, β-DIBROMOSUBSTITUTED DERIVATIVES

Thirty eight new compounds of β-(5-nitro-2-furyl)propionamides and their α, β-dibromo-substituted derivatives were prepared. The β-(5-nitro-2-furyl) propionamides (Ⅱ) were prepared from the corresponing acrylamides by catalytic hydrogenation and the β-(5-nitro-2-furyl)-α,β-dibromosubstituted propionamides (Ⅲ) were obtained from the corresponding acrylamides by bromination under suitable conditions.Twenty-one compounds of Ⅲ were found to possess pronounced activity against Schistomiasis japonica in mice, but none of Ⅱ revealed any significant activity. Among the former, compound Ⅲ₂₄ was shown to be most effective and is now under clinical trial.