Methotrexate analogues. 20. Replacement of glutamate by longer-chain amino diacids: Effects on dihydrofolate reductase inhibition, cytotoxicity, and in vivo antitumor activity

Article abstract of DOI:10.1021/jm00366a012

Chain-extended analogues of methotrexate were synthesized by condensation of 4-amino-4-deoxy-N¹⁰-methylpteroic acid with esters of L-α-aminoadipic, L-α-aminopimelic, and L-α-aminosuberic acids, followed by ester hydrolysis with acid or base. Co