Quinazolines as inhibitors of dihydrofolate reductase. 4. Classical analogues of folic and isofolic acids.
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 and chlorasquin as well as 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.
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D005493:Folic Acid Antagonists; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000188:drug therapy; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D011799:Quinazolines / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D013291:Streptococcus / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D011799:Quinazolines; D005492:Folic Acid