Pyrazine derivatives: a patent review (June 2012 – present)

Abstract

Pyrazine derivatives possess numerous noteworthy pharmacological effects, including antimycobacterial, antibacterial, antifungal, antidiabetic, diuretic, anticancer, antiviral, hypnotic, and analgesic. The class of pyrazine-based candidate drugs has experienced a rapid growth both in absolute numbers of investigated compounds and in the spectrum of diverse biological activities. We expect that several of these compounds will add to existing pharmaceuticals in the very near future. According to the number of compounds and filed patents, the most promising areas are: i) inhibitors of protein kinases (applicable as antiproliferatives); and ii) inhibitors of β-secretase (applicable for the treatment of Alzheimer's disease).

Substituted N-(Pyrazin-2-yl)benzenesulfonamides; Synthesis, Anti-Infective Evaluation, Cytotoxicity, and In Silico Studies

“…However, they were excluded from the comparison as they-unlike the other compounds-possessed the pharmacophore for the inhibition of folate pathway, which was proven by docking studies. We performed target fishing, where we identified matrix metalloproteinase-8 as a promising target for our title compounds that is worth future exploration.Molecules 2020, 25, 138 2 of 20 several compounds containing a pyrazine core directly connected to a sulfonamide moiety-like in our case-are already documented in the literature with a wide range of pharmacological applications [9]. Examples (Figure 2) include zibotentan, an endothelin receptor antagonist with antitumor activity for prostate cancer [10]; halogenated N-(pyrazinyl)benzenesulfonamides, which are clathrin-coated pit (CCP) chemokine receptor antagonists used in treating chemokine mediated diseases (such as asthma) [11]; and sulfamethoxypyrazine (sulfalene), which is an antibacterial sulfonamide agent [12].…”

“…Nevertheless, Generally, sulfonamides exert a wide range of biological activities, including anti-tumoral [5], anti-inflammatory [6], anti-convulsant [7], and anti-infective [8], among others. Nevertheless, several compounds containing a pyrazine core directly connected to a sulfonamide moiety-like in our case-are already documented in the literature with a wide range of pharmacological applications [9]. Examples ( Figure 2) include zibotentan, an endothelin receptor antagonist with antitumor activity for prostate cancer [10]; halogenated N-(pyrazinyl)benzenesulfonamides, which are clathrin-coated pit (CCP) chemokine receptor antagonists used in treating chemokine mediated diseases (such as asthma) [11]; and sulfamethoxypyrazine (sulfalene), which is an antibacterial sulfonamide agent [12].…”

Enzymatic Cascade in Pseudomonas that Produces Pyrazine from α‐Amino Acids

“…Pyrazines are aromatic heterocyclic compounds with 1,4‐nitrogen atom substituents in benzene that are widely applied as flavors, perfumes, pharmaceuticals, and raw materials for chemicals . They are synthesized through common chemical reactions and many natural pyrazines have been isolated over the past 70 years .…”

Synthesis and Characterization of 2‐(2‐Pyridinyl)pyrazine and 2,2′‐Bipyrazine Derivatives

“…A central goal of chemical synthesis is to develop efficient and reliable methods for making nitrogen‐contained heterocycles. Among nitrogen heterocycles, the derivatives of pyrazine and bipyrazine motives have attracted considerable attention, as it is present in many bacterial studies , food, agriculture, medicine , and as ligands in coordination chemistry .…”