Neville M C, Verge J P
J Med Chem. 1977 Jul;20(7):946-9. doi: 10.1021/jm00217a017.
Ten 2-substituted 4-thiazolecarboxaldehyde hydrazones bearing 5-nitro-2-furyl, 5-nitro-2-thiazolyl, and 1-methyl-5-nitro-2-imidazolyl functions have been prepared and screened for activity against Trypanosoma cruzi infections in mice. The results permitted the ranking of these substituents in decreasing order of activity: 1-methyl-5-nitro-2-imidazolyl greater than 5-nitro-2-furyl greater than 5-nitro-2-thiazolyl, the last being inactive. Some structural features of the side chain necessary for optimum activity are discussed. The most active compound, 4-[[[2-(1-methyl-5-nitro-2-imidazolyl)-4-thiazolyl]methylene]amino]thiomorpholine 1,1-dioxide, compared favorably with the standard Nifurtimox against three recent clinical isolates of T. cruzi, including one with a high myocardial tissue infiltration.
已制备了十种带有5-硝基-2-呋喃基、5-硝基-2-噻唑基和1-甲基-5-硝基-2-咪唑基官能团的2-取代-4-噻唑甲醛腙，并对其抗小鼠克氏锥虫感染的活性进行了筛选。结果得出这些取代基按活性递减顺序排列为：1-甲基-5-硝基-2-咪唑基＞5-硝基-2-呋喃基＞5-硝基-2-噻唑基，最后一个无活性。讨论了最佳活性所需侧链的一些结构特征。最具活性的化合物4-[[[2-(1-甲基-5-硝基-2-咪唑基)-4-噻唑基]亚甲基]氨基]硫代吗啉1,1-二氧化物，与标准药物硝呋替莫相比，对三种近期克氏锥虫临床分离株表现良好，其中包括一株心肌组织浸润严重的分离株。
