抗疟新药的研究——具有对-氨基酚双Mannich碱的杂环化合物的合成

作者等将对-氨基酚双Mannich碱的侧链与苯骈[g]喹啉、1,5-萘啶、吡啶骈[2,3-d]嘧啶,苯骈[c]吖啶、吡啶骈[2,3-c]吖啶以及吡啶骈[2,3-e]吖啶等杂环相连,合成了不同类型的杂环化合物V_1～19。部分化合物经鼠疟Plasmodium berghei试验,发现化合物V_{1～3,8,10,12,18}等具有杀灭红细胞内期裂殖体的作用。部分化合物用约氏原虫(P.yoelii)-斯氏按蚊(Anophelesstephensi)-鼠模型筛选,未见有明显作用。

STUDIES ON NEW ANTIMALARIALS——SYNTHESIS OF HETEROCYCLIC COMPOUNDS CARRYING DOUBLE MANNICH BASIC CHAINS OF p-AMINOPHENOL

This paper presents the preparation of heterocyclic compounds V_1～19 carrying double Mannich basic side chains of p-aminophenol. These heterocyclic nuclei are benzo [g] quinoline, 1,5-naphthyridine, pyrido[2,3-d]pyrimidine, benzo[c]acridine, pyrido[2,3-c] acridine and pyrido[2,3-e]acridine. Compounds V_1～19 were synthesized from the heterocyclic intermediates a～f by condensing with p-aminophenol. Products Ⅵ carrying p-aminophenoi reacted further with Mannich reagents to yield the desired compounds.Compounds V_{1～3, 6, 8～15, 19} were tested for blood schizonticidal activity against Plasmodium berghei in mice. The results showed that compounds V_{1～3, 8, 10, 12, 19} were rather effective. In addition, compounds V_{4～10, 16, 19} did not show any activity in P. yoelii-Anopheles stephensi-mouse model.