Synthesis and Evaluation of 1,2,4-Triazolo[1,5-a]pyrimidines as Antibacterial Agents Against Enterococcus faecium

Rapid emergence of antibiotic resistance is one of the, most Challenging global public health concerns. In particular; vancomycin-resistant Enterococcus faecium infections have been increasing in frequency, representing 25% of enterococci infections in intensive care units. A novel class of 1,2,4-triazolo[1,5-a]pyrimidines active against E. faecium is reported herein We used a three component Biginelli-like heterocyclization reaction for the synthesis of a series of these derivatives based on reactions of aldehydes, beta-dicarbonyl compounds, and 3-alkylthio-5-amino-1,2,4-triazoles. The resulting compounds were assayed for,antimicrobial activity against the ESKAPE panel of bacteria, followed by investigation of their in vitro activities. These analyses identified :a subset of 1,2,4-triazolo[1,5-a]pyrimidines that had good narrow spectrum antibacterial activity against E faecium and exhibited metabolic stability with low intrinsic clearance. Macromolecular synthesis assays revealed cell-wall biosynthesis as the target of these antibiotics.