抗疟药的研究——ⅩⅥ.2,4-二氨基-6-[(取代苯基)硫代、亚硫酰、硫酰]喹唑啉类化合物的合成及抗疟作用

2,4-二氨基喹唑啉类化合物为叶酸拮抗剂,对多种动物疟原虫有较好的作用。Elsla-ger等报道2,4-二氨基-6-(间-三氟甲苯基)硫代]喹唑啉(Ⅰ)对鸡疟(Plasmodiumgallinaceum)子孢子和鼠疟(Plrsmodium berghei)滋养体均有较好的杀灭作用,对乙胺嘧啶敏感的Oak Knoll株和抗乙胺嘧啶的马来亚Camp株感染的枭猴也有治愈作用。鉴于三氟甲基在抗疟药中的独特作用和喹唑啉亚硫酰、硫酰类化合物(Ⅱ)对鼠疟有较好作用的

STUDIES ON ANTIMALARIAL AGENTS ⅩⅥ. SYNTHESES AND ANTIMALARIAL ACTIVITIES OF 2, 4-DIAMINO-6-[(SUBSTITUTED PHENYL)THIO, SULFINYL AND SULFONYL] QUINAZOLINES

2,4-Diamino-6-(substitutedphenyl) thio]quinazolines (Ⅶa～d) were prepared via condensation of 2-nitro-5-chlorobenzonitrile with substituted thiophenols, followed by reduction with stannous chloride and cyclization with chloroformamidine hydrochloride or cyano guanidine. Oxidation of Ⅶa～c with hydrogen peroxide afforded corresponding sulfinyl and sulfonyl derivatives(Ⅷa～c and Ⅸa～c) , The compounds were screened for suppressive antimalarial activity against P. berghei in mice and for causal prophylactic action against P. yoelii in mice. With the exception of Ⅶa,d and Ⅷa, all compounds exhibited marked antimalarial activity against blood induced plasmodium berghei in mice. Compounds Ⅶc, Ⅷb,c and Ⅸc suppressed parasitemia at 1.25 mg/kg. Compounds Ⅷb,c and Ⅸb,c were shown to have causal prophylactic activity against P. yoelii at 1.25 mg/kg and 0.625 mg/kg. Among them Ⅷc was the most potent. It suppressed parasitemia at 0.3125 mg/kg and was shown to have prophylactic activity at 0.078 mg/kg.