2,4-二氨基-5-氯-6-取代苄氨基喹唑啉类化合物的合成及其抗疟、抗肿瘤和抗菌活性

本文报道标题化合物的合成及其抗疟、抗肿瘤和抗菌活性,该类化合物是以5-氯-2,4, 6-三氨基喹唑啉与各种取代苯甲醛缩合成相应的Schiff碱,然后经NaBH₄还原,再甲酰化或亚硝化制得.经对感染伯氏疟原虫(P.berghei)的鼠抑制性治疗筛选,有八个化合物剂量20mg/kg×4d时抑制率100%,Ⅰ₃,Ⅰ₄,Ⅲ₄三个化合物剂量5mg/kg×4d时抑制率在90%以上;体外抗肿瘤试验有4个化合物的活性优于MTX和SIPl759,以Ⅰ₄最佳。对L1210白血病细胞株的IC₅₀为2.20×10^-9 m mol/L;经对18种常用菌株进行体外筛选,发现对肺炎双球菌(D.pneumoniae)有较好的活性。

SYNTHESIS AND BIOLOGICAL ACTIVITIES OF 2,4-DIAM I-NO-5- CHLORO-6- SUBSTITUTED QUINAZOLINES

Title compounds were synthesized by condensation of 5-chloro-2,4,6-triaminoquinazoline (8) with various substituted benzaldehydes to produce the corresponding Schiff bases, followed by reduction with NaBH4, II and III were obtained by formylation or nitrosation of I respectively. Primary screening for suppressive therapeutic effects against P. berghei in mice showed that eight of the twelve compounds produced 100% suppression when administered orally at dose of 20 mg/kg. The results against L1210 Leukemia cell and B16 melanoma cell in vitro exhibited potent inhibition. Among them four compounds were more active than MTX and SIPI 759. Further work is in process. Antibacterial tests in vitro showed that a number of compounds possessed moderate activities against Diplococcus pneumoniae.