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2,4-二氨基喹唑啉类化合物为叶酸代谢拮抗剂,文献曾报道了许多具有较好抗疟作用的这类化合物,2,4-二氨基-6-取代氨基磺酰喹唑啉亦属此类。我们曾于1974年合成了这一类化合物,其中2,4-二氨基-6-吡咯烷基磺酰喹唑啉(I_(11))皮下给药20mg/Kg对感染鸡疟(P. gallinaceum)的小鸡有病因性预防作用。2,4-二氨基-6-环己氨基磺酰喹唑啉(I_9)对感染鼠疟(P. berghei)的小鼠皮F给药10mg/Kg有治愈作用。最近发现I_9对鼠疟抗氯喹株的效果优于敏感株,皮下给药SD_(50)分别为1.7mg/Kg和2.9mg/Kg。为了继续观察这类化合物对鼠疟(P. berghei)抗氯喹株的治疗作用和对鼠疟(P. yoelii)的病因性预防作用,以及进一步研究其构效关系,作者等又合成了具有下列通式的取代氨基磺酰喹唑啉类化合物。
2,4-diaminoquinazoline compounds for the folic acid metabolism antagonists, the literature has reported many such compounds have good anti-malarial effects, 2,4-diamino-6-substituted aminosulfonylquinazoline also Is this. We have synthesized this kind of compound in 1974, in which 2,4-diamino-6-pyrrolidinylsulfonylquinazoline (I_ (11)) subcutaneously administered 20 mg / Kg against P. gallinaceum ) Chickens have a causal preventive effect. 2,4-Diamino-6-cyclohexylaminosulfonylquinazoline (I_9) had a healing effect on P. berghei mouse skin F administration of 10 mg / Kg. Recently I_9 was found to be more potent against chloroquine against murine malaria than the susceptible strain, and the SD 50 was 1.7 mg / kg and 2.9 mg / kg, respectively. In order to further observe the therapeutic effect of these compounds against P. berghei chloroquine resistant strains and the etiologic preventive effect on P. yoelii and to further investigate their structure-activity relationship, the authors synthesized the following compounds with the following Substituted aminosulfonylquinazolines of the general formula.