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 ¹H nmr and ¹³C nmr. The growth of leukemia L1210 cells in culture was inhibited about 50% by 4,5,6 and 7 at 100 μM.