Lysine and ornithine analogues of methotrexate as inhibitors of dihydrofolate reductase.

ID: ALA1122157

Journal: J Med Chem

Title: Lysine and ornithine analogues of methotrexate as inhibitors of dihydrofolate reductase.

Authors: Kempton RJ, Black AM, Anstead GM, Kumar AA, Blankenship DT, Freisheim JH.

Abstract: 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.

CiteXplore: 7069726

DOI: 10.1021/jm00346a026

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