Folate antagonists. 12. Antimalarial and antibacterial effects of 2,4-diamino-6-[(aralkyl and alicyclid)thio-, sulfinyl-, and sulfonyl]quinazolines

• Published in: Journal of medicinal chemistry 1978-07, Vol.21 (7), p.639-643
• Main Authors: Elslager, E F, Davoll, J, Jacob, P, Johnson, A M, Johnson, J, Werbel, L M
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - chemical synthesis; Antimalarials - chemical synthesis; Antimalarials - therapeutic use; Enterococcus faecalis - drug effects; Folic Acid Antagonists - chemical synthesis; Folic Acid Antagonists - pharmacology; Folic Acid Antagonists - therapeutic use; Malaria - drug therapy; Mice; Microbial Sensitivity Tests; Plasmodium berghei; Quinazolines - chemical synthesis; Quinazolines - pharmacology; Quinazolines - therapeutic use; Staphylococcus aureus - drug effects
• ISSN: 0022-2623
• DOI: 10.1021/jm00205a009

A series of 2,4-diamino-6-[(aralkyl and alicyclic)thio-, sulfinyl-, and sulfonyl]quinazolines was prepared via condensation of 5-chloro-2-nitrobenzonitrile or 5,6-dichloro-2-nitrobenzonitrile with the appropriate aralkyl or alicyclic thiopseudourea, reduction of the resulting 2-nitro-5-[(aralkyl or alicyclic)thio]benzonitrile with stannous chloride to the amine, and cyclization with chloroformamidine hydrochloride. Oxidation was effected with hydrogen peroxide or the bromine complex of 1,4-diazabicyclo[2.2.2]octane. These analogues when examined for suppressive activity against drug-sensitive lines of Plasmodium berghei in mice were not as active as 2,4-diamino-6-[3,4-dichlorobenzyl)amino]quinazoline (Ia).