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.[a] K.

Synthesis and Anti‐inflammatory Effect of Simple 2,3‐Diarylindoles. On Route to New NSAID Scaffolds

“…Synthetic methods for accessing to this class of active compounds involves in general, the use of metal free [12–24] or metal catalyzed [25,26] strategies. In the context of this work, we referred to indomethacin, as an indole‐containing drug, considered one of the most efficient anti‐inflammatories which acts as non‐selective COX‐1 and COX‐2 inhibitor [27] . Also, is one of the most important NSAID‐containing the indol core, broadly used the last half century.…”

“…Also, is one of the most important NSAID‐containing the indol core, broadly used the last half century. Due to its efficacy as anti‐inflammatory, several strategies have been developed for its total synthesis [27] as well as some structural modifications at the carboxylic acid, [28–32] C‐2, [33,34] C‐5 [35] and nitrogen [36–37] (Figure 1B). One of the main indomethacin inconveniences is the adverse effects on the gastrointestinal (GI) tract due to the action over COX‐1 [38,39] …”

Synthesis andin vivoEvaluation of Fluorobenzyl Metformin Derivatives as Potential Drugs in The Diabetes Treatment

“…This discipline has been evolving with time, increasing the development of compounds with high pharmaceutical interest, using strategies such as metal-catalyzed, [1,2] metalfree [3][4][5][6][7][8][9][10] or natural occurring compounds synthesis and derivatization. [11][12][13] These compounds have been developed with specific goals, such as for the treatment of cancer, [14,15] mycoses, [16] polycystic ovarian, pain, inflammation [17] hyper-glycemia and lastly but not less important: diabetes mellitus. This can be considered as a group of chronic metabolic illnesses, [17] characterized by a higher blood glucose level, impaired lipid metabolism, low insulin concentration given an initial insulin resistance, and consequently the β pancreatic cells deterioration.…”

Iodine(III)‐Aluminum or ‐Ammonium Salts for the Oxidative Aromatic Inorganic Functionalization

“…In this REDOX process, the aromatic ring is oxidized and the external oxidant agent is reduced at the end of the transformation. It's worth highlighting the biological relevance by introducing inorganic groups such as halogens or nitro groups, since their presence on the aromatic rings it confers a wide range of activities such as anti‐diabetic, [8–10] fungistatic, [11] anti‐inflammatory, [12,13] anti‐nociceptive, [14–19] or as potential drugs in the cancer treatment, [20–23] or MDR‐reversers [24] among others (Figure 1).…”