N-哌嗪基烷基取代的8-氨基喹啉类的合成及其抗疟作用

SYNTHESIS AND ANTIMALARIAL ACTIVITIES OF (?)-PIPERAZINYLALKYL-8-AMINOQUINOLINE DERIVATIVES

为寻找高效低毒的8-氨基喹啉类抗疟新药,用1-[(3-氯丙基)-4-(氨基烷基)]哌嗪在三乙胺存在下与环上取代的8-氨基喹啉缩合,合成了一系列 N-哌嗪基烷基取代的8-氨基喹啉类化合物(1~20)。其中多数对鼠伯氏疟原虫感染的抑制性治疗均具一定的活性,在20mg/kg×4d 的剂量下,化合物1,6,10和19的原虫抑制率为100%。在病因性预防筛选中,化合物1,18和19可使感染约氏疟原虫子孢子的实验鼠全部得到保护。化合物1在10mg/kg×3d 的剂量下仍有4/5的实验鼠保持阴性,仍比伯喹为优。

In an effort to search for a more effective,less toxic 8-aminoquinolineantimalarial,a series of 4-methyl,2-,or 5-phenoxy-and 2,5-diphenoxy-6-methoxy-8-〔3-[4-(aminoalkyl)piperazin-1-yl]propylamino〕quinolines(1~20)have been prepared.1~20 were obtained by condensing 8-aminoquinoline with 1-(3-chloropropyl)-4-(aminoalkyl)piperazine hydrochloride in the presence of triethylamine.Most of the compounds showed significant blood schizonticidal activity againstPlasmodium berghei,among which 1,6,10 and 19 were 100% curative at a dose of20 mg/kg.In causal prophylactic screening test against P.yoelii,1,18 and 19 gave5/5 cures at a dose of 20 mg/kg,and 1,which still gave 4/5 cures at 10 mg/kg,seemed superior to primaquine.