Microwave-assisted synthesis of pyrimido[4,5-b][1,6]naphthyridin-4(3H)-ones with potential antitumor activity

The 6,7,8,9-tetrahydropyrimido[4,5-b][1,6]naphthyridin-4(3H,5H,10H)-ones 4,5a–g and their oxidized forms 6,7a–g were obtained from the catalyst-free reaction of 6-amino-2-methylthiopyrimidin-4(3H)-one 3 and (E)-3,5-bis(benzylidene)-1-alkyl-4-piperidones 1,2a–g under Microwave irradiation and their subsequent oxidation process with p-chloranil. Eighteen of the new compounds were evaluated in the US National Cancer Institute (NCI), where compound 4g presented a remarkable activity against 57 cancer cell lines, with the most important GI50 values ranging from 1.48 to 9.92 μM from in vitro assays.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Novel pyrimido[4,5-b][1,6]naphthyridines were obtained by microwave-assisted synthesis under catalyst-free conditions. ► Naphthyridines 6 and 7 were oxidized by treatment of pyrimido[4,5-b][1,6]naphthyridine 4 and 5 with p-chloranil. ► Compounds 4–7 were screened by the US (NCI) against 60 different human tumor cell lines. ► Compound 4g showed a remarkable in vitro activity with GI50 = 1.48 μM and LC50 > 100 M.