疟疾防治药物的研究——Ⅶ.2,4-二哌啶(或吡咯啶)基-6-取代氨基喹唑啉衍生物的合成及其抗疟作用

本文报道2,4-二哌啶(或吡咯啶)基-6-取代氨基喹唑啉衍生物的合成及其抗疟作用。该类化合物经伯氏鼠疟原虫(Plasmodium berghei)抑制性治疗和约氏鼠疟原虫(P.yoelii)病因性预防筛选,发现有16个化合物对感染约氏鼠疟原虫的小鼠有病因性预防作用,其中以Ⅵ₁₁,Ⅷ₁,Ⅸ₂及Ⅸ₄四个化合物效果最好,每天口服2.5 mg/kg,连续三天,可使小鼠得到完全保护。此类化合物的合成,是以2,4-二氯-6-硝基喹唑啉与哌啶或吡咯啶缩合,经还原得2,4-二哌啶(或吡咯啶)基-6-氨基喹唑啉,然后与相应的取代苯甲醛缩合成席夫氏碱,再经还原和亚硝化而制得。

STUDIES ON ANTIMALARIALS Ⅶ.SYNTHESIS AND ANTIMALARIAL ACTIVITIES OF SOME DERIVATIVES OF 2,4-DIPIPERIDINO- OR 2,4-DIPYRROLIDINO-6-(SUBSTITUTED) AMINO-QUINAZOLINES

The reported 2,4-dipiperidino-or 2, 4-dipyrrolidino-6-(substituted) aminoquinazolines were synthesized as potentialantimalarial agents. These compounds were. prepared by reaction of 2,4-dichloro-6-nitroquinazoline with piperidine or pyrrolidine, followed by hydrogenation to form 2,4-dipiperidino-6-aminoquinazoline (Ⅷ₁) or 2,4-dipyrrolidino-6-aminoquinazoline (Ⅷ₂), Ⅷ₁ and Ⅷ₂ condensed respectively with substituted benzaldehydes to afford the corresponding Schiff's bases from which compounds Ⅵ were obtained through hydrogenation and nitrosation. Preliminary screening tests were conducted for both therapeutic and prophylactic activities of these compounds on mice infected either with Plasmodium berghei or P. yoelii. Out of these compounds 16 were shown to possess more or less causal prophylactic activity against P. yoelii. Among them, four compounds (Ⅵ₁₁, Ⅷ₁, Ⅸ₂, Ⅸ₄) were more effective and shown to protect the test mice from being infected at oral doses of 2.5mg/kg in 3 consecutive days.