Folate antagonists. 11. Synthesis and antimalarial effects of 6-[(aryloxy- and arylthio-)methyl]-2,4-pteridinediamines and -pteridinediamine 8-oxides.
Condensation of 3-amino-6-(bromomethyl)-2-pyrazinecarbonitrile 4-oxide with 4-chlorophenol gave 3-amino-6-[(4-chlorophenoxy)methyl]-2-pyrazinecarbonitrile 4-oxide (1), which was deoxygenated to obtain the de-N-oxide 4. Cyclization of 4 and 1 produced 6-[(4-chlorophenoxy)methyl]-2,4-pteridinediamine and the 8-oxide, respectively. 6-[(Arylthio)methyl]-2,4-pteridinediamines and their 8-oxides were produced analogously. Controlled oxidation of the former gave the anticipated sulfoxide 12 and sulfone 13. None of these compounds showed significant activity when tested against lethal Plasmodium berghei infections in mice or a select list of bacteria in vitro.
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects; D003959:Diamines / Q000138:chemical synthesis / Q000494:pharmacology; D005493:Folic Acid Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D008826:Microbial Sensitivity Tests; D010962:Plasmodium berghei; D011621:Pteridines / Q000138:chemical synthesis* / Q000494:pharmacology
D000962:Antimalarials; D003959:Diamines; D005493:Folic Acid Antagonists; D011621:Pteridines