TFAA/H3PO4‐Mediated C‐2 Acylation of Thiophene: A Direct Synthesis of Known and Novel Thiophene Derivatives of Pharmacological Interest

Abstract

A number of aliphatic and aromatic carboxylic acids were reacted with thiophene in the presence of trifluoroacetic anhydride and H3PO4 to give a variety of acylated thiophenes in good to excellent yields. The methodology was used to prepare known nonsteroidal anti‐inflammatory drug‐based novel compounds of potential pharmacological significances. Molecular modeling studies were carried out by using nonsteroidal anti‐inflammatory drug‐based thiophene derivatives to assess their cyclooxygenase inhibiting potential in silico. On the basis of docking studies followed by subsequent in vitro assay, indomethacin‐based thiophene derivative was identified as a novel cyclooxygenase‐2 inhibitor with balanced selectivity.