Several a-and y-monoesters of methotrexate (MTX) were synthesized chemically and evaluated as inhibitors of cultured human lymphoblastic leukemia (CCRF-CEM) cells and purified dihydrofolate reductase (DHFR) from rabbit liver. Chemical methods included direct HC1-catalyzed half-esterification of MTX, partial cleavage of methotrexate diesters in the presence of base, and mixed anhydride coupling from 4-amino-4-deoxy-No-methylpteroic ...
