Pyrazine and Phenazine Heterocycles: Platforms for Total Synthesis and Drug Discovery

Abstract

There are numerous pyrazine and phenazine compounds that demonstrate biological activities relevant to the treatment of disease. In this review, we discuss pyrazine and phenazine agents that have shown potential therapeutic value, including several clinically used agents. In addition, we cover some basic science related to pyrazine and phenazine heterocycles, which possess interesting reactivity profiles that have been on display in numerous cases of innovative total synthesis approaches, synthetic methodologies, drug discovery efforts, and medicinal chemistry programs. The majority of this review is focused on presenting instructive total synthesis and medicinal chemistry efforts of select pyrazine and phenazine compounds, and we believe these incredible heterocycles offer promise in medicine.

Reactivity of 4-Bromoacetyl-1,2,3-triazoles towards Amines and Phenols: Synthesis and Antimicrobial Activity of Novel Heterocycles

“…[2][3][4][5] The synthesis of heterocycles containing pyrazine ring systems is therefore of wide interest. [6][7][8][9] The traditional method for the synthesis of pyrazines involves the use of 1,2-diketones in the presence of ammonia to produce the corresponding diamines or aminoketones followed by condensation and oxidation. [10][11][12][13] They can also be produced using -haloor hydroxy-ketones, 14,15 2H-azirines, 16 and nitro epoxides.…”

An insight into therapeutic efficacy of heterocycles as histone‐modifying enzyme inhibitors that targets cancer epigenetic pathways

“…Heterocyclic compounds are the class of organic compounds that include 3–9 membered rings having the same or different elements (Huigens 3rd. et al, 2022; Sharma et al, 2021). Naturally, inspired molecules majorly constitute heterocycles (He, Gao, et al, 2021; Jeelan Basha et al, 2022).…”

Improve the Crosslinking Reactivity of Nitrile: Design of Nitrile‐Functionalized Pyrazine and its Hydrogen Bond‐Assisted Nucleophilic Enhancement Study

“…[40] Therefore, molecular engineering of pyrazines has also been applied in drug synthesis and food engineering. [41,42] Compared with the benzene ring, pyrazine is more prone to nucleophilic reaction due to its electronic withdrawing effect. [43] The abundant hydrogen bonding sites (additional nitrogen atoms) in pyrazine are also revealed for enzymatic efficiency in biochemistry through proximity effects.…”