• regioselectivity
• SARS-CoV-2
• triazoles
• triazolization

Finding novel antiviral medications to stop the SARS-CoV-2 virus from spreading has become essential in light of the COVID-19 pandemic. The critical role that the 3CLpro enzyme plays in viral replication has made it an attractive target for therapy. The 3CLpro enzyme has no homolog in humans so it is an ideal target for antiviral therapy with weak side effects. Specifically, it has been demonstrated in the past that 1,2,3-triazole derivatives are effective against the coronavirus 229E 3CLpro enzyme. Because it can establish crucial contacts with the catalytic dyad of the 3CLpro binding site, the benzotriazole group is very significant. Our work focuses on the synthesis of compounds that have already been demonstrated to be active against the 3CLpro of coronavirus 229E in order to determine whether this activity also applies to the SARS-CoV-2 virus which is responsible for the COVID-19 pandemic. Additionally, we synthesized a novel library of 1,2,3-triazole derivatives in order to identify compounds with potentially useful medicinal applications. The synthesis of the triazole derivatives was carried out using the triazolization process, a click chemistry technique that our lab had previously developed. Easily accessible enolizable ketones, primary amines, and 4-nitrophenilazide (4-NPA) are used as reagents in this one-pot triazolization method. In addition, unlike other 1,2,3-triazole synthesis techniques, it does not require starting materials that are difficult to come by or cytotoxic metallic catalysts like copper. For these reasons, triazolization is the synthetic way we chose to synthesize our derivatives. Both the new compounds and the already existing compounds were then subjected to biological tests to show their activity against SARS-CoV-2 3CLpro and their cytotoxicity.