An efficient synthesis of pyrrolo[3′,2′:4,5]thiopyrano[3,2-b]pyridin-2-one: a new ring system of pharmaceutical interest

A series of pyrrolo[3′,2′:4,5]thiopyrano[3,2-b]pyridin-2-ones 4 was prepared in good yields by reacting enaminoketones with cyanomethylene active compounds such as phenylsulfonylacetonitrile, benzoylacetonitrile, and malononitrile. Derivatives of the title ring system were tested by the National Cancer Institute of Bethesda against a panel of about 60 human tumor cell lines, and one of them showed inhibitory activity against all cancer cell lines reaching on 48% of them GI50 values at submicromolar level and on the majority of the remaining ones in the low micromolar concentration.

Several derivatives of the new ring system pyrrolo[3′,2′:4,5]thiopyrano[3,2-b]pyridin-2-ones 4 have been prepared in good yields. Our synthetic approach consisted in the reaction of enaminoketones with cyanomethylene active compounds. The antiproliferative activity of the new compounds was investigated against the NCI full panel of about 60 human cancer cell lines and one of them showed antitumor activity against all the tested cell lines reaching on 48% of them GI50 values at submicromolar level.