SYNTHESIS OF A PYRIDO[2,3-(D)UNDER-BAR]PYRIMIDINE ANALOG OF THE MULTITARGETED ANTIFOLATE LY2315314

Syntheses of pyrido[2,3-d]pyrimidines (9) and (21), ring-expanded anal ogues of the antitumor agent LY231514 (7), and its 4-amino analog, res pectively, are described. Preliminary in vitro cell culture evaluation has shown that expansion of the pyrrole ring of the latter two pyrrol o[2,3-d]pyrimidines through introduction of a carbonyl group between p ositions 6 and 7 results in complete loss of cell growth inhibitory ac tivity.