Uses of ethyl benzoyl acetate for the synthesis of thiophene, pyran, and pyridine derivatives with antitumor activities

Abstract

AbstractThe N‐(arly)propanamide derivatives 3a,b were used for a series of heterocyclization reactions to give thiophene, pyran, and pyridine derivatives. Thus, these compounds underwent the Gewald's thiophene synthesis through their reactions with either malononitrile or ethyl cyanoacetate and elemental sulfur to afford compounds 6a‐f, respectively. In addition, they were subjected through a series of multicomponent reactions (MCRs) to give pyran and fused derivatives. The reactions of 3a,b with either malononitrile or ethyl cyanoacetate gave pyridine derivatives 14a‐d, respectively. The latter compounds afforded arylhydrazone derivatives 15a‐m through their reactions with any of the aromatic diazonium salts 15a‐c. The antitumor of the synthesized compounds against A549 (nonsmall cell lung cancer), H460 (human lung cancer), HT‐29 (human colon cancer), and MKN‐45 (human gastric cancer cancer) cancer cell lines together with foretinib as the positive control by a MTT assay was measured, and the results obtained showed that many compounds exhibited high potency against the six cancer cell lines.