Quinoxaline chemistry: Part 9. Quinoxaline analogues of trimetrexate (TMQ) and 10-propargyl-5,8-dideazafolic acid (CB 3717) and its precursors. Synthesis and evaluation of in vitro anticancer activity

Article abstract of DOI:10.1016/S0014-827X(98)00002-0

Eighteen quinoxalines bearing a methyleneanilino or methyleneaminobenzoylglutamate group on position 6 of the ring and various lipophilic substituents on positions 2 and 3 were prepared in order to discover if their structural analogy with both trimetrexate (TMQ) and 10-propargyl-5,8-dideazafolic acid (CB 3717) might display in vitro anticancer activity. Among these, 12 compounds were selected at the National Cancer Institute, Bethesda, MD, USA; they exhibited moderate (4b,d,i,l,m and 8) to strong (4f,h and 5a,e) cell-growth inhibition at a concentration of 10^-4 M. Interesting selectivities were also recorded between 10^-8 and 10^-6 M. These analogues proved to be less potent inihibitors of tumor cells than other classical and non-classical antifolate analogues previously described by us.