Process Improvement on the Synthesis of Nolatrexed;

Nolatrexed was synthesized from 2-bromo-4-nitrotoluene via seven steps and compound I and II were synthesized from intermediate 4 or 5 respectively .

Synthesis of Anticancer Drug Nolatrexed;

Synthesis of nolatrexed dihydrochloride;

Effect of nolatrexed on the thymidylate synthase mRNA expression in three tumor cell lines;

Antiproliferative effect of nolatrexed on cell line SRS-82 in vitro and in vivo;

Effects of nolatrexed on thymidylate synthase protein expression;

Synergistic anticancer wffect of 5-azacytidine combined with nolatrexed dihydrochloride in vitro;

Phase Ⅰ clinical trial of nolatrexed dihydrochloride in patients with solid tumors;

Measurement of plasma concentration and bioavailability of nolatrexed dihydrochloride in mice;