4－甲基－5－取代苯氧基－伯氨喹类似物的合成及抗疟活性的初步评价

SYNTHESIS OF 4-METHYL-5-SUBSTITUTED PHENOXY- PKIMAQUINE ANALOGUES AND PRELIMINARY EVALUATION ON THEIR ANTIMAL ARIAL ACTIVITY

摘要: 以2-硝基-4-甲氧基-5-溴乙酰苯胺为原料，经6步反应，合成了7个4-甲基-5-取代苯氧基伯氨喹类似物(Ⅱ_2～8)。抗疟活性的初步评价结果表明，这类化合物对鼠疟 Plasmodium yoelii 的病因性预防作用明显优于伯氨喹．可达伯氨唪的4～8倍；同时，Ⅱ_2～8还有较强的杀血液裂殖体作用．Ⅱ_2,5,6,8在0.781 mg·kg^-1 的剂量对原虫的抑制率为100％。

Abstract: On basis of our previous work, seven 4-methyl-5-substituted Dhcnoxy-6-methoxy-8-(l-methyl-4-amino-butylamino)-quirtdines(Ⅱ_2～8)were synthesized and their antimalarial activities were preliminarily evaluated．The target compounds were prepared from 2-nitro-4-methoxy-5-bromo-aceXanilide as previously described．The structures 0f Ⅱ_2～8 and all of the unknow intermediates were confirmed by elementary and spectral analyses．Preliminary biological evaluation revealed that all of Ⅱ_2～8 exhibited significant blood schizontieidal activity and were 4～8 times as effective as primaquine in causal prophylactic test in mice．