Quinazolines as inhibitors of dihydrofolate reductase. 4. Classical analogs of folic and isofolic acids

Abstract

A series of classical quinazoline analogues of folic and isofolic acids was evaluated for inhibitory activity against the dihydrofolate reductases from rat liver and from Streptococcus faecium. Included in this group were the known active antitumor agents methasquin, chlorasquin and methotrexate. Two new compounds, N10-formyl-5,8 deazaaminopterin and N10-formyl-5,8-deazafolic acid, were synthesized specifically for this study. The latter displayed modest activity against L1210 leukemia in mice.