Synthesis and Antitumor Activity against HepG-2, PC-3, and HCT-116 Cells of Some Naphthyridine and Pyranopyridinecarbonitrile Derivatives

A series of substituted and fused heterocyclic derivatives 2-17 were synthesized using 3,5-bis(4-methoxybenzylidene)-1-propylpiperidin-4-one (1) as starting material. Treatment of 1 with malononitrile or semicarbazide afforded compounds 2 and 3, respectively. Condensation of 1 with ethyl cyanoacetate afforded naphthyridine-3-carbonitrile derivative 4, which reacted with phosphorus pentachloride and phosphoryl chloride to give chloro derivative 5. Treatment of 5 with thiosemicarbazide afforded compound 6. The reaction of 1 with malononitrile gave cyano aminopyrane derivative 7 which was condensed with pyromellitic dianhydride, phthalic anhydride, succinic anhydride, or morpholine in glacial acetic acid to obtain imide derivatives 8-11. Additionally, the reaction of 7 with aromatic aldehydes gave derivatives 12a-12c. Acetylation of 7 with acetic anhydride in boiling acetic acid gave N-acetyl derivative 13 which was cyclized to pyridine derivative 14 by refluxing in dioxane in the presence of triethylamine. Treatment of 7 with hydrazine hydrate gave pyrazolo derivative 15. Finally, the reaction of 7 with triethyl orthoformate in the presence of acetic anhydride gave formimidate 16 which was treated with hydrazine hydrate to form N-amino derivative 17. Some of the synthesized compounds were examined in vitro for their antitumor activity against HepG-2, PC-3, and HCT-116 human carcinoma cell lines using MTT assay.