Over the years, 1,2,4-Triazolo[1,5-a]pyrimidine (TP) emerged as an important scaffold in medicinal chemistry due to its vast application in designing novel anticancer, antimicrobial, antiviral, antiparasitic, and CNS-modulating agents. Recently, publications of TP analogues with diverse biological activities have increased markedly. In this review, we focus on the most important applications of TP scaffold in medicinal chemistry.

TP scaffold has emerged as a prominent scaffold in developing promising anti-cancer agents acting on multiple oncoargets such as DNA damage repair system, signal transduction pathway, ubiquitin-proteasome pathway (UPP), epigenetic modification, tumor microenvironment (TME), and multidrug resistance (MDR). Also, TP analogues provide promising candidates for treating different central nervous system (CNS) diseases acting through inhibition of acetylcholine esterase or phosphodiestrase 2A (PDE2A) or by Stabilizing Microtubules. Moreover, it represents a good pharmacophore for developing different candidates that have been acting as potent anti-infectious diseases such as(antibacterial, antiparasitic, and antiviral agents) over the recent years.