Synthesis of some substituted tetrahydropyrimido[4,5‐ b ][1,6]naphthyridines as potential antitumor agents

Cyclocondensation of two disubstituted 6‐aminopyrimidines 11 and 12 with 1‐benzyl‐3‐hydroxymethylene‐4‐piperidone afforded new tricyclic, linear disubstituted 6,7,8,9‐tetrahydropyrimido[4,5‐ b ][1,6]naphthyridines 4 and 5 respectively. Similar cyclocondensation of 11 with 1‐benzoyl‐1,2,3,6‐tetrahydropyridine‐5‐carboxalde‐hyde gave the corresponding benzoylated tetrahydropyrimido[4,5‐ b ][1,6]naphthyridine 6 . Debenzoylation of 6 afforded 7 . 1‐Benzyl‐3‐aminomethylene‐4‐piperidone when cyclocondensed with 11 also afforded 4 . The linear structures were established by 1 H nmr and 13 C nmr. The growth of leukemia L1210 cells in culture was inhibited about 50% by 4,5,6 and 7 at 100 μM.