Indomethacin Synthesis, Historical Overview of Their Structural Modifications

Abstract One of the most important (NSAID) non‐steroidal anti‐inflammatory drug‐containing the indol core is represented by the indomethacin. This highly relevant compound has been used for the last 50 years with excellent pharmacological results. Due to its relevant efficacy as an anti‐inflammatory treatment, several syntheses have been developed during this half of century. Herein is summarized and discussed the most representative strategies which successfully addressed the total syntheses of indomethacin as well as some of its derivatives generated by carrying out strategic modifications at the nitrogen atom, the carboxylic acid at C‐3, the methoxy group at C‐5 and the methyl group at C‐2.