Synthesis of 2‐Organylchalcogenopheno[2,3‐b]pyridines from Elemental Chalcogen and NaBH4/PEG‐400 as a Reducing System: Antioxidant and Antinociceptive Properties

An alternative method to prepare 2‐organylchalcogenopheno[2,3‐b]pyridines was developed by the insertion of chalcogen species (selenium, sulfur or tellurium), generated in situ, into 2‐chloro‐3‐(organylethynyl)pyridines by using the NaBH4/PEG‐400 reducing system, followed by an intramolecular cyclization. It was possible to obtain a series of compounds with up to 93 % yield in short reaction times. Among the synthesized products, 2‐organyltelluropheno[2,3‐b]pyridines have not been described in the literature so far. Moreover, the compounds 2‐phenylthieno[2,3‐b]pyridine (3 b) and 2‐phenyltelluropheno[2,3‐b]pyridine (3 c) exhibited significant antioxidant potential in different in vitro assays. Further studies demonstrated that compound 3 b exerted an antinociceptive effect in acute inflammatory and non‐inflammatory pain models, thus indicating the involvement of the central and peripheral nervous systems on its pharmacological action. More specifically, our results suggest that the intrinsic antioxidant property of compound 3 b might contribute to attenuating the nociception and inflammatory process on local injury induced by complete Freund's adjuvant (CFA). Don't be such a pain! The synthesis of 2‐organylchalcogenopheno[2,3‐b]pyridines was promoted by a chalcogen/NaBH4/PEG‐400 system. These compounds were obtained in moderated to good yields. Among the synthesized products, compound 3 b exhibited a promising antinociceptive effect in different animal models, probably due to its intrinsic antioxidant property.