Folate antagonists. 16. Antimalarial and antibacterial effects of 2,4-diamino-6-[(heterocyclic)thio,sulfinyl, and sulfonyl]quinazolines

The reaction of 5-chloro-2-nitrobenzonitrile with a variety of mercaptoheterocycles provided the corresponding 2-nitro-5-(heterocyclic)thio]benzonitriles. Reduction to the amine followed by cyclization with chloroformamidine hydrochloride afforded a series of 2,4-diamino-6-(hetero-cyclic)thio]quinazolines. Bromination, oxidation, and amidine formation were accomplished with 2,4-diamino-6-(4-phenyl-2-thiazolyl)thio]quinazoline (23) to provide additional analogs. Several of these compounds exhibited suppressive antimalarial activity against drug-sensitive lines of Plasmodium berghei in mice.