Prodrugs of Non-steroidal Anti-inflammatory Drugs (NSAIDs): A Long March Towards Synthesis of Safer NSAIDs.

As a therapeutic group, non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used, prescribed and over the counter (OTC) medications for the treatment of inflammatory diseases, but suffering from several undesired side effects, the most important being ulcerogenicity, mucosal hemorrhage and gastritis. Most of the NSAID moieties are chemically composed of carboxylic functional groups and this could be one of the reasons for the damage to the mucosal lining. The prodrug designing is one of the several strategies used to overcome this drawback. Hence, in the last decade, the design and the synthesis of prodrugs of NSAIDs have been explored and given much attention by medicinal chemists. The rationale behind the prodrug concept is to achieve temporary blockade of the free carboxylic group present in the NSAIDs till their systemic absorption. This review is aimed to highlight and provide important information on NSAID prodrugs that have been designed and reported to be safe and more effective. This review will also focus on NSAID prodrugs that have been designed for improving therapeutic i.e. anti-inflammatory action as well as improving drug delivery at the target site. The most common derivatives of carboxylic NSAIDs that are discussed here belong to the chemical classes of esters, amides, anhydrides, acetals and the other derivatives with completely masked carboxylic groups. The successful prodrugs were listed and their molecular structures were also demonstrated here. The present review covers the recent updates present in literature and will surely provide a greater insight into the designing of safer NSAIDs in the future.