Chen C, Zheng X Y, Guo H Z
Institute of Parasitic Diseases, Chinese Academy of Preventive Medicine, Shanghai.
Yao Xue Xue Bao. 1993;28(8):594-8.
The paper reports the synthesis of pyronaridine (I) related compounds II-V for exploring whether the antimalarial activity of pyronaridine is by virtue of a nitrogen atom at position 1 in the ring and a pair of pyrrolidinyl Mannich base side chains in its structure. The condensation of 2-methoxy-6,9-dichloroacridine or 4,7-dichloro-1,5-naphthyridine with 4-hydroxy-3,5-bis-(pyrrolidinyl-1'-methyl) aniline yielded the related compound II, 1-deazapyronaridine, or V, 5-azabispyroquine, respectively. 2-Methoxy-7,10-dichlorobenzo (b) 1,5-naphthyridine or 4,7-dichloro-1,5-naphthyridine was condensed with 4-diethylamino-1-methylbutylamine to obtain the related compound III, azacrin, or IV, 5-azachloroquine, respectively. The results of in vivo tests against Plasmodium berghei chloroquine-resistant ANKA strain, drug-sensitive P. berghei N line and drug-resistant P. yoelii nigeriensis line showed that all the related compounds II-V were less effective than pyronaridine (I). It suggests that the nitrogen atom at position 1 and pyrrolidinyl Mannich base side chains on the structure of pyronaridine play an important and indispensable role for antimalarial activity of pyronaridine. The pyrrolidinyl Mannich bases impart increased activity to the corresponding compounds.
该论文报道了咯萘啶（I）相关化合物II - V的合成，以探究咯萘啶的抗疟活性是否归因于其结构中环上1位的氮原子和一对吡咯烷基曼尼希碱侧链。2 - 甲氧基 - 6,9 - 二氯吖啶或4,7 - 二氯 - 1,5 - 萘啶与4 - 羟基 - 3,5 - 双 -（吡咯烷基 - 1'-甲基）苯胺缩合分别得到相关化合物II，1 - 去氮咯萘啶，或V，5 - 氮杂双咯喹啉。2 - 甲氧基 - 7,10 - 二氯苯并（b）1,5 - 萘啶或4,7 - 二氯 - 1,5 - 萘啶与4 - 二乙氨基 - 1 - 甲基丁胺缩合分别得到相关化合物III，氮杂吖啶，或IV，5 - 氮杂氯喹。针对伯氏疟原虫氯喹抗性ANKA株、药物敏感的伯氏疟原虫N株和抗药的约氏疟原虫尼日尔株的体内试验结果表明，所有相关化合物II - V的效果均不如咯萘啶（I）。这表明咯萘啶结构中1位的氮原子和吡咯烷基曼尼希碱侧链对咯萘啶的抗疟活性起着重要且不可或缺的作用。吡咯烷基曼尼希碱使相应化合物的活性增强。
