疟原虫组织期裂殖体杀灭剂的研究:5-三氟乙酰基伯氨喹及其衍生物的合成  

STUDIES ON THE TISSUE SCHIZONTICIDE OF MALARIA PARASITE:SYNTHESIS OF 5-TRIELUOROACETYL PRIMAQUINE AND ITS DERIVATIVES

作　　者：郑贤育 陈昌[1] 房文[1] 

机构地区：[1]中国预防医学科学院寄生虫病研究所,上海200025

出　　处：《药学学报》1992年第6期423-427,共5页Acta Pharmaceutica Sinica

摘　　要：伯氨喹与三氟乙酸酐作用,可制得相应的N-三氟乙酰基伯氨喹(2),也可形成双-(三氟乙酰基)伯氨喹(化合物6),后者再水解,生成5-三氟乙酰基伯氨喹,简称三氟乙酰伯氨喹(11)。化合物1,3～5以及7～10,均按上法分别制得。其中以化合物11杀灭鼠、猴疟原虫组织期裂殖体的作用最强,对小鼠的急性毒性比伯氨喹低2倍。是一种值得研究的疟原虫组织期裂殖体杀灭剂。Primaquine was acylated with trifluoroacetic anhydride to give 6-methoxy-8-(4-trifluoroacetamido-1-methylbutyl) aminoquinoline (compound 2 inTable)and 5-trifluoro-acetyl-6-methoxy-8-(4-trifluoroacetamido-1-mehylbutyl)aminequinoline (compound 6), bis (trifluoroacetyl) primaquine, which was subsequentlyhydrolyzed to yield 5-trifluoroacetyl-6-methoxy-8-(4-amino-1-methylbutyl)aminoquinoline (compound 11),5-trifluoroacetyprimaquine or trifluoroacetoprima-quine, coded M8506. Similarly, compounds 1, 3～5 and 7～l0 were also prepared. Among them, compound 11 appeared to be the most effective by evaluation in miceinfected with sporozoites of Plamodium yoelii. With intragastrical dosage of 0.75 mg/kg/d×3 d of compound 11 to monkeys infected with sporozoites of P. cynomolgi, the radicalcure rate of the compound was 92.3%, while that of primaquine was 55.6%. The acute toxicity of compound 11 was two times as low as that of Primaquine in mice. The compound did not appear to have mutagenicity, embryotoxicity and chromosomalaberrtion. When rats received intragastrical doses of 15, 30 and 60 mg/kg/d of compound 11 for 14 and 28 consecutive days respectively, no change was found inhistopathological examination at the two lower doses. However, reversible changes wereobserved at the highest dose. Compound 11, trifluoroacetoprimaquine, was shownto be a promising tissue schizonticide of malaria parasite.

关 键 词：疟原虫杀灭剂 伯氨喹 

分 类 号：R978.61[医药卫生—药品]