Synthesis of some 1,3,8‐trisubstituted pyrimido[4,5‐c][2,7]‐naphthyridin‐6‐ones as potential antitumor agents

Condensation of three 2,4‐disubstituted 6‐aminopyrimidines with methyl 1‐benzyl‐4‐oxo‐3‐piperidinecarboxylate afforded, in each case, new tricyclic, angular 1,3,8‐trisubstituted pyrimido[4,5‐c][2,7]naphthyridin‐6‐ones. 2,4,6‐Triaminopyrimidine gave the 7,8,9,10‐tetrahydrocyclo condensed product 5 as anticipated. However, the use of 2‐amino‐4‐oxo‐ or 2,4‐dioxo‐6‐aminopyrimidine afforded the dehydrogenated, 9,10‐dihydrotricyclic products 11 and 12. The growth of leukemia L1210 cells in culture were inhibited 50% by the 1,3‐diamino analog 5 at 2 × 10⁻⁶M and by the 1,3‐dioxo analog 12 at 10⁻⁵M.