疟疾防治药物的研究——Ⅰ.2,4-二氨基-5-取代氨基嘧啶和2,4-二氨基-6-甲基-5-取代氨基嘧啶衍生物的合成及其抗疟作用

本文报道2,4-二氨基-5-取代氨基嘧啶和2,4-二氨基-6-甲基-5-取代氨基嘧啶衍生物的合成及其抗疟活性的研究。这类化合物的合成是分别以2,4,5-三氨基嘧啶或2,4,5-三氨基-6-甲基嘧啶与相应的取代的苯甲醛缩合成席夫氏碱,然后经还原,亚硝化或甲酰化制得。经鼠疟原虫-斯氏按蚊系统的病因性预防初筛,发现有12个化合物有效,其中2,4-二氨基5-[(3′,4′-二氯代苯亚甲基)-氨基]嘧啶(化合物V₃)和2,4-二氨基-5-[(4′-溴代苄基)-N-亚硝基-氨基]嘧啶(化合物Ⅶ₄)效果最好,口服10 mg/kg共三天,可使小白鼠得到保护,血中未查见原虫。

STUDIES ON ANTIMALARIALS Ⅰ. SYNTHESIS AND ANTIMALARIAL ACTIVITIES OF SOME DERIVATIVES OF 2,4-DIAMINO-5-SUBSTITUTED AMINO PYRIMIDINES AND 2,4-DIAMINO-6-METHYL-5-SUBSTITUTED AMINO PYRIMIDINES

The synthesis of a series of 2,4-diamino-5-substituted amino pyrimidines and 2,4-diamino-5-substituted amino pyrimidines were carried out by condensation of 2,4,5-triaminopyrimidines or 2,4,5-triamino-6-methyl pyrimidines with substituted benzaldehydes to form the corresponding Schiff' bases, followed by hydrogenation, nitrosation or formylation.Using plasmodium yoelii-Anopheles stephensi system, these compounds were primarily screened for their causal prophylactic activities against the parasites. Out of these compounds 12 were found to possess antimalarial effect of varying degrees. Two of them,2,4-diamino-5-(3′,4-dichloro-benzlidene amino)pyrimidine (compound Ⅴ₃) and 2,4-diamino-5-[(4′-bromo-benzyl)-N-nitroso-amino] pyrimidine (compound Ⅶ₄) administered orally at a dose of 10 mg/kg in 3 consecutive days (D₀～D₂) were more effective than the remaining ten, as shown by the protection of the tested mice from being infected.