Das B P, Wallace R A, Boykin D W
J Med Chem. 1980 May;23(5):578-81. doi: 10.1021/jm00179a022.
2,5-Bis(4-guanylphenyl)-1,3-oxazole, 2,5-bis(4-guanylphenyl)-1,3,4-oxadiazole and -1,3,4-thiadiazole, and 3,6-bis(4-guanylphenyl)pyridazine and several of their "cyclic guanyl" analogues have been synthesized. 2,5-Bis(4-guanylphenyl)-1,3-oxazole and -1,3,4-thiadiazole showed good activity, whithout acute toxicity, against Trypanosoma rhodesiense in mice, producing cures at a 3 mg/kg dosage level. This activity is comparable to stilbamidine, hydroxystilbamidine, and pentamidine in this test. In contrast, 2,5-bis(4-guanylphenyl)-1,3,4-oxadiazole shows a sharp reduction in activity in our test system. Generally, the cyclic guanyl analogues exhibit low orders of activity, and toxicity begins to appear at moderate dosage levels. All guanyl and cyclic guanyl compounds were synthesized from bisnitrile precursors by way of imidate ester hydrochlorides in a classical Pinner-type approach.
已合成了2,5-双(4-胍基苯基)-1,3-恶唑、2,5-双(4-胍基苯基)-1,3,4-恶二唑和-1,3,4-噻二唑，以及3,6-双(4-胍基苯基)哒嗪及其几种“环状胍基”类似物。2,5-双(4-胍基苯基)-1,3-恶唑和-1,3,4-噻二唑对小鼠体内的罗德西亚锥虫显示出良好活性且无急性毒性，在3mg/kg剂量水平时能治愈感染。在该试验中，此活性与锥虫胂胺、羟基锥虫胂胺和喷他脒相当。相比之下，2,5-双(4-胍基苯基)-1,3,4-恶二唑在我们的测试系统中活性急剧降低。一般而言，环状胍基类似物活性较低，在中等剂量水平时开始出现毒性。所有胍基和环状胍基化合物均通过经典的平纳型方法，由双腈前体经亚氨酸酯盐酸盐合成。
