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) thioquinazolines (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.