Synthesis of Novel 1,4-Dihydropyrido[3′,2′:5,6]thiopyrano[4,3-c]pyrazoles and 5H-Pyrido[3′,2′:5,6]thiopyrano[4,3-d]pyrimidines as Potential Antiproliferative Agents.

The synthesis of new planar derivatives characterized by the presence of a pyridothiopyranopyrazole or pyridothiopyranopyrimidine nucleus, carrying a substituted aryl group, is reported. The novel 1,4-dihydropyrido[3′,2′:5,6]thiopyrano[4,3-c]pyrazole derivatives were obtained by condensation of 2,3-dihydro-3-hydroxymethylenethiopyrano[2,3-b]pyridin-4(4H)-ones with appropriate hydrazines. The preparation of 2-substituted pyrido[3′,2′:5,6]thiopyrano[4,3-d]pyrimidines was accomplished from the intermediate 2,3-dihy-dro-3-dimethylaminomethylenethiopyrano[2,3-b]pyridin-4(4H)-ones by reaction with the appropriate binucleophile amidines. The antiproliferative activity of some new products was tested by an in vitro assay on human tumour cell lines (HL-60 and HeLa), but none of them showed any significant effects in the tests performed. Accordingly, linear flow dichroism measurements indicated their inability to form a molecular complex with DNA.