Recent Advances in Process Development of Antiviral Agents Targeting the Influenza Virus: Amantadine-RemantadineDerived Pharmaceutical Agents

This short review summarizes our work on the process development for the synthesis of amontidine remantadine. The M2 proton channel of the influenza A virus is the target of the anti-influenza drugs amantadine and rimantadine. The effectiveness of these drugs has been dramatically limited by the rapid spread of drug resistant mutations, mainly at sites S31N, V27A and L26F in the pore of the channel. Despite progress in designing inhibitors of V27A and L26F M2, there are currently no drugs targeting these mutated channels in clinical trials. The article traces the evolution of various synthesis approaches and provides a comparison for overall yield efficiency. Amantadine hydrochloride is an antiviral drug used in prevention and treatment of influenza a infections. It has also been used for alleviating early symptoms of Parkinson's disease. Several methods for the preparations of Amantadine hydrochloride have been reported. Overall yields ranging from 50 to 52%. In this article, we describe procedure for the synthesis of Amantadine hydrochloride from via N-(1- adamantyl) acetamide with an improved yield of 60% the procedure was also optimized to reduce the use of toxic solvents and reagents, rendering it more environment-friendly. The procedure can be considered as suitable for largescale production of amantadine hydrochloride.