Mondal_2025_Future.Med.Chem__1

The triazolopyrazine scaffold is characterized by fused triazole and pyrazine rings. It represents a highly versatile, nitrogen-rich heterocyclic framework extensively explored as a prominent scaffold that is of greater importance for developing novel drugs with various biological activities because they may present several structural alterations with identical numbers of carbon and nitrogen atoms. The triazolopyrazine scaffold has broad-spectrum biological activities, including antimalarial, anticancer, antidiabetic, antimicrobial, antifungal, antiviral, and neurological activity. As a result, numerous investigators have synthesized these compounds as target structures and assessed their biological activities. Its broad biological profile has always been a subject of interest, attracting researchers to investigate the distinctive features of this skeleton. In recent years, remarkable progress has been made in the medicinal chemistry of triazolopyrazine-based derivatives. The current review aims to provide research progress on triazolopyrazine hybrids, including structure-activity relationship (SAR) and target interaction analysis, which will pave the way for the design and development of new, novel target-selective triazolopyrazine derivatives as promising agents. This versatile and structurally unique framework of triazolopyrazine scaffold will benefit researchers and medicinal chemists engaged in exploring the triazolopyrazine scaffold as a future lead for drug design and discovery.