Lysine and ornithine analogues of methotrexate as inhibitors of dihydrofolate reductase.
The ornithine (6a) and lysine (6b) analogues of methotrexate (1) have been synthesized via condensation of 4-amino-4-deoxy-N10-methylpteroic acid (2) with N gamma-carbobenzoxy-L-ornithine tert-butyl ester (3a) and N epsilon-carbobenzoxy-L-lysine tert-butyl ester (3b), respectively. Removal of the protecting groups gave 5a and 6b. Compounds 6a and 6b and their precursor Cbz acids (5a and 5b) show significant inhibition of dihydrofolate reductase.
D055598:Chemical Phenomena; D002621:Chemistry; D005493:Folic Acid Antagonists; D008727:Methotrexate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D005493:Folic Acid Antagonists; C034334:lysine-methotrexate; C034333:ornithine-methotrexate; D008727:Methotrexate