Quinoxaline chemistry. Part 4. 2(R)-anilinoquinoxalines as nonclassical antifolate agents. Synthesis, structure elucidation and evaluation of in vitro anticancer activity.

Thirty-five quinoxalines bearing a substituted aniline group on position 2 and various substituents on positions 3,6,7 and 8 were prepared in order to evaluate in vitro anticancer activity. Structural elucidation of some isomeric quinoxalinones formed by ring closure of 4-substituted-1,2-diaminobenzenes with dicarbonyl compounds was achieved by comparison with one isomer coming from an unambiguous independent route. Preliminary in vitro screening at NCI showed that many compounds exhibited a moderate to strong growth inhibition activity on various cell lines between 10(-5) and 10(-4) molar concentrations.