Synthesis and Antibacterial Activity of Novel Triazolo[4,3-a]pyrazine Derivatives

Abstract

Infectious diseases pose a major challenge to human health, and there is an urgent need to develop new antimicrobial agents with excellent antibacterial activity. A series of novel triazolo[4,3-a]pyrazine derivatives were synthesized and their structures were characterized using various techniques, such as melting point, 1H and 13C nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis. All the synthesized compounds were evaluated for in vitro antibacterial activity using the microbroth dilution method. Among all the tested compounds, some showed moderate to good antibacterial activities against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli strains. In particular, compound 2e exhibited superior antibacterial activities (MICs: 32 μg/mL against Staphylococcus aureus and 16 μg/mL against Escherichia coli), which was comparable to the first-line antibacterial agent ampicillin. In addition, the structure–activity relationship of the triazolo[4,3-a]pyrazine derivatives was preliminarily investigated.

Sequential, Electrochemical‐Photochemical Synthesis of 1,2,4‐Triazolo‐[4,3‐a]pyrazines

“…An alternative route that avoids direct formation of the hydrazinesubstituted pyrazine via chlorinated precursors is via the ring opening of a 1,2,4-oxadiazole with ethylenediamine to obtain the hydrazine-substituted piperazine. [28] Cyclization of this hydrazine-substituted piperazine in the presence of concentrated hydrochloric acid yields the desired 1,2,4-triazolo-[4,3a]pyrazine. Unfortunately, this route still requires the handling of hydrazine to synthesize the 1,2-diacetyl hydrazine necessary for 1,2,4-oxadiazole formation.…”