Synthesis of the antileukemic agents 5,10-dideazaaminopterin and 5,10-dideaza-5,6,7,8-tetrahydroaminopterin.
Total syntheses from pyridine precursors of 5,10-dideazaaminopterin (1) and 5,10-dideaza-5,6,7,8-tetrahydroaminopterin (2) are described. These compounds exhibit significant in vivo activity against L1210 leukemia that is comparable to that observed with methotrexate.
D019732:Amide Synthases; D000630:Aminopterin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D005492:Folic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis; D005493:Folic Acid Antagonists; D007938:Leukemia / Q000188:drug therapy*; D007939:Leukemia L1210 / Q000188:drug therapy; D008025:Ligases / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D013763:Tetrahydrofolates / Q000138:chemical synthesis; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors
D005493:Folic Acid Antagonists; D013763:Tetrahydrofolates; C045894:lometrexol; C045893:5,10-dideazafolic acid; D005492:Folic Acid; C045892:5,10-dideazaaminopterin; C045891:5,10-dideaza-5,6,7,8-tetrahydroaminopterin; D013940:Thymidylate Synthase; D008025:Ligases; D019732:Amide Synthases; C024383:pteroylpolyglutamate synthase; D000630:Aminopterin; D008727:Methotrexate