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European Journal of Medicinal Chemistry Oct 2023Heterocycles are common in the structure of drugs used clinically to deal with diseases. Such drugs usually contain nitrogen, oxygen and sulfur, which possess... (Review)
Review
Heterocycles are common in the structure of drugs used clinically to deal with diseases. Such drugs usually contain nitrogen, oxygen and sulfur, which possess electron-accepting capacity and can form hydrogen bonds. These properties often bring enhanced target binding ability to these compounds when compared to alkanes. Pyrazine is a nitrogen-containing six-membered heterocyclic ring and many of its derivatives are identified as bioactive molecules. We review here the most active pyrazine compounds in terms of their structure, activity in vitro and in vivo (mainly antitumor activity) and the reported mechanisms of action. References have been downloaded through Web of Science, PubMed, Science Direct, Google Scholar and SciFinder Scholar. Publications reporting only the chemistry of pyrazine derivatives are beyond the scope of this review and have not been included. We found that compounds in which a pyrazine ring was fused into other heterocycles especially pyrrole or imidazole were the highly studied pyrazine derivatives, whose antineoplastic activity had been widely investigated. To the best of our knowledge, this is the first review of pyrazine derivatives and their bioactivity, especially their antitumor activity. This review should be useful for those engaged in development of medications based on heterocyclic compounds especially those based on pyrazine.
Topics: Pyrazines; Heterocyclic Compounds; Antineoplastic Agents; Nitrogen
PubMed: 37300915
DOI: 10.1016/j.ejmech.2023.115544 -
Food Chemistry Jan 2024Pyrazines are a class of active aromatic substances existing in various foods. The accumulation of pyrazines has an impact on flavor and quality of food products. This... (Review)
Review
Pyrazines are a class of active aromatic substances existing in various foods. The accumulation of pyrazines has an impact on flavor and quality of food products. This review encompasses the formation mechanisms and control strategies of pyrazines via Maillard reaction (MR), including the new reactants and emerging techniques. Pyrazines characteristics are better understood through the developed sample pretreatments and detection methods. Herein, an in-depth review of pretreatments and analysis methods since 2010 is presented to explore the simple, fast, green, and effective strategies. Sample preparation methods include liquid phase extraction, solid phase extraction, supercritical fluid extraction, and microextraction methods such as liquid phase microextraction, and solid phase microextraction, etc. Detections are made by chromatographic methods, and sensors, etc. Advantages and limitations are discussed and compared for providing insights to further studies.
Topics: Pyrazines; Solid Phase Extraction; Liquid-Liquid Extraction; Solid Phase Microextraction; Chromatography, Supercritical Fluid
PubMed: 37566982
DOI: 10.1016/j.foodchem.2023.137086 -
Proceedings. Biological Sciences Nov 1990Of the various types of alerting signals found in nature, odours are the least well understood. The worldwide distribution of pyrazines in plants, insects, terrestrial... (Review)
Review
Of the various types of alerting signals found in nature, odours are the least well understood. The worldwide distribution of pyrazines in plants, insects, terrestrial vertebrates, marine organisms, fungi and bacteria suggests that they are of special significance. We speculate that these molecules served as natural points of convergence in the evolution of widespread alerting signals, which are used for differing but related intraspecific purposes by various species. In aposematic, self-advertising toxic insects and their mimics, for example, pyrazines function as additional warning signals; preliminary data indicates that their odour can potentiate taste aversion learning in rats and the associative learning of immune suppression in mice. The latter suggests that in addition to their alerting properties, pyrazine odours may act as ectohormones which interact with predator physiology.
Topics: Animals; Immune System; Learning; Odorants; Pheromones; Pyrazines
PubMed: 1981616
DOI: 10.1098/rspb.1990.0113 -
Applied Microbiology and Biotechnology Feb 2010Pyrazines are a class of compounds that occur almost ubiquitously in nature. Pyrazines can be synthesised chemically or biologically, and are used as flavouring... (Review)
Review
Pyrazines are a class of compounds that occur almost ubiquitously in nature. Pyrazines can be synthesised chemically or biologically, and are used as flavouring additives. The major formation of pyrazines occurs during heating of food. There is very little information available on the degradation of these compounds. In humans and animals, pyrazines are excreted as glucuronates or bound to glutathione via the kidney after hydroxylation, but the pyrazine ring is not cleaved. Bacteria have been isolated, which are able to use various substituted pyrazines as a sole carbon and energy source. In a few cases, the initial metabolites have been characterised; however, the mechanism of ring cleavage and the further degradation pathways are still unknown and await further investigation.
Topics: Animals; Bacteria; Biodegradation, Environmental; Carbon; Flavoring Agents; Humans; Hydroxylation; Industrial Waste; Molecular Structure; Odorants; Pyrazines
PubMed: 19957079
DOI: 10.1007/s00253-009-2362-4 -
Food Chemistry Jul 2022The generation of pyrazines in a binary methionine/glucose (Met/Glc) mixture and corresponding methionine/glucose-derived Amadori rearrangement product (MG-ARP) was...
The generation of pyrazines in a binary methionine/glucose (Met/Glc) mixture and corresponding methionine/glucose-derived Amadori rearrangement product (MG-ARP) was studied. Quantitative analyses of pyrazines and methional revealed that MG-ARP generated more methional compared to Met/Glc, whereas lower content and fewer species of pyrazines were observed in the MG-ARP model. Comparing the availability of α-dicarbonyl compounds generated from the Met/Glc model, methylglyoxal (MGO) was a considerably effective α-dicarbonyl compound for the formation of pyrazines during MG-ARP degradation, but glyoxal (GO) produced from MG-ARP did not effectively participate in the corresponding formation of pyrazines due to the asynchrony on the formation of GO and recovered Met. Diacetyl (DA) content was not high enough to form corresponding pyrazines in the MG-ARP model. The insufficient interaction of precursors and rapid drops in pH limited the formation of pyrazines during MG-ARP degradation. Increasing reaction temperature could reduce the negative inhibitory effect by promoting the content of precursors.
Topics: Glucose; Glyoxal; Maillard Reaction; Methionine; Pyrazines
PubMed: 35245757
DOI: 10.1016/j.foodchem.2022.132500 -
Chemical & Pharmaceutical Bulletin 2022Knoevenagel condensation, an olefin-forming reaction from active methyl/methylene-containing compounds and aldehydes, is a fundamental and useful synthetic method....
Knoevenagel condensation, an olefin-forming reaction from active methyl/methylene-containing compounds and aldehydes, is a fundamental and useful synthetic method. Benzothiazoles are, however, out of the scope of Knoevenagel condensation. Here, we report that Knoevenagel condensation between aldehydes and 2-methyl-thiazolo[4,5-b]pyrazines (MeTPy), a fused ring structure comprising pyrazine and thiazole, proceeded smoothly, despite minor structural differences from benzothiazoles. This finding will be useful for short synthesis of MeTPy-containing functional molecules, such as a tau probe analog 1.
Topics: Aldehydes; Alkenes; Molecular Structure; Pyrazines
PubMed: 34980738
DOI: 10.1248/cpb.c21-00780 -
Accounts of Chemical Research Aug 2021Pyrazinacenes are a class of nitrogen-containing heteroacene molecules composed of linearly fused pyrazine units, which might also include dihydropyrazine groups leading... (Review)
Review
Pyrazinacenes are a class of nitrogen-containing heteroacene molecules composed of linearly fused pyrazine units, which might also include dihydropyrazine groups leading to different reduced states of the compounds. While they are structurally similar to hydrocarbon acenes (e.g., pentacene) the presence of increasing numbers of N-heteroatoms introduces several different additional features of the compounds so that they can be considered for investigations beyond those suggested for acenes (i.e., organic field-effect transistors, solar cell components). Pyrazinacenes are in several ways complementary to C-H-only acenes based on the increasing stability of reduced states of the compounds with increasing numbers of fused pyrazine rings, although an acene-like electronic structure persists in the compounds so far studied. However, the introduction of multiple N atoms leads to properties that depart from C-H-only acenes. In particular, the compounds exhibit a delocalization of NH protons in extended reduced compounds and oxidation state switchability in solution and at interfaces. The presence of NH groups also allows an easy introduction of solubilizing groups at the pyrazinacene chromophore. In this Account, we will describe the preparation of extended pyrazinacenes from dipyrazino[2,3-b:2',3'-e]pyrazine (1,4,5,8,9,10-hexaazaanthracene; ) derivatives up to 1,4,5,6,7,8,9,12,13,14,15,16,17,18-tetradecaazaheptacene () and also assess structures of the relevant compounds based on X-ray crystallographic studies. Emergent properties of the molecules include highly unusual linear tautomeric processes based on a delocalization of protons (and the corresponding formation of orbitals based on multiple adjacent N lone electron pair interactions), which suggest special transport properties based on molecular protonics. Molecules such as decazapentacene () exhibit multistability of oxidation state, and this is predicted to promote the redox catalytic properties of the compounds. The oxidation-state switching of on-surface processes is also described and has been investigated using scanning tunneling microscopy. The longest known pyrazinacene chromophore () exhibits amphiprotism with its state of protonation being strongly coupled to its fluorescence emission properties in the near-infrared region indicating possible uses in pH-coupled bioimaging applications. The synthesis of the pyrazinacenes is flexible and allows the preparation of symmetrically or unsymmetrically substituted derivatives for the development of more complex molecules and for control of the electronic structure of the acene unit. Overall, the pyrazinacenes represent an emerging class of highly nitrogenous heteroacenes with unique properties and excellent potential for development in different applications based on their special supramolecular properties including guest binding or interactions in biological systems.
Topics: Crystallography, X-Ray; Heterocyclic Compounds; Molecular Structure; Oxidation-Reduction; Pyrazines; Spectrophotometry, Ultraviolet
PubMed: 34323462
DOI: 10.1021/acs.accounts.1c00315 -
Angewandte Chemie (International Ed. in... Dec 2018Herein we report the biocatalytic synthesis of substituted pyrazines and pyrroles using a transaminase (ATA) to mediate the key amination step of the ketone precursors....
Herein we report the biocatalytic synthesis of substituted pyrazines and pyrroles using a transaminase (ATA) to mediate the key amination step of the ketone precursors. Treatment of α-diketones with ATA-113 in the presence of a suitable amine donor yielded the corresponding α-amino ketones which underwent oxidative dimerization to the pyrazines. Selective amination of α-diketones in the presence of β-keto esters afforded substituted pyrroles in a biocatalytic equivalent of the classical Knorr pyrrole synthesis. Finally we have shown that pyrroles can be prepared by internal amine transfer catalyzed by a transaminase in which no external amine donor is required.
Topics: Molecular Structure; Pyrazines; Pyrroles; Transaminases
PubMed: 30335228
DOI: 10.1002/anie.201810555 -
Yakugaku Zasshi : Journal of the... Jan 1997This review deals with syntheses and reactions of pyrazines, especially, of 2,5-disubstituted pyrazines. The description was made in due to order of 1) synthesis and... (Review)
Review
This review deals with syntheses and reactions of pyrazines, especially, of 2,5-disubstituted pyrazines. The description was made in due to order of 1) synthesis and properties of 2,5-disubstituted pyrazines, 2) synthesis of 2,5-disubstituted pyrazine N-oxides, 3) synthesis of pyrazinols, 4) synthesis and utilization of pyrazinethiols; preparation of aldehydes, utilization as an acyl carrier, and preparation of olefins via the elimination of pyrazinylsulfinyl group, 5) synthesis of aminopyrazines, 6) synthesis of azidopyrazines and their transformation to imidazoles, 7) palladium-catalyzed reactions of chloropyrazines; dechlorination, introduction of cyano, alkenyl, alkynyl, alkyl, and aryl groups to the pyrazine ring. The cross-coupling of chloropyrazines with aromatic heterocycles such as furan, thiophene, pyrroles, indoles, benzo[b]furan, benzo[b]thiophene, oxazole, thiazole, benz[b]oxazole, and benzo[b]thiazole is also described.
Topics: Pyrazines
PubMed: 9120799
DOI: 10.1248/yakushi1947.117.1_1 -
Water Research Sep 2020The presence of earthy-musty odors in drinking water is a major concern for water suppliers and consumers worldwide. While geosmin and 2-methylisoborneol are the most...
The presence of earthy-musty odors in drinking water is a major concern for water suppliers and consumers worldwide. While geosmin and 2-methylisoborneol are the most studied earthy-musty odor-causing compounds, pyrazine and its alkyl and methoxy compounds possess similar odors and are widely distributed in nature, foods, and beverages. In this study, odor characteristics of pyrazines and their presence in natural and treated waters were determined. Pyrazine, 2,6-dimethyl-pyrazine (DMP), 2,3,5-trimethyl-pyrazine (TrMP), 2-ethyl-5(6)-methyl-pyrazine (EMP), 2,3,5,6-tetramethyl-pyrazine (TeMP), 2-isobutyl-3-methoxy-pyrazine (IBMP) and 2-isopropyl-3-methoxy-pyrazine (IPMP) were measured in source and finished drinking water across China. 2-Methoxy-3,5-dimethyl-pyrazine (MDMP), IBMP, and IPMP were investigated in rivers in Virginia, USA. The results showed that "musty" and "sweet" were the most common descriptors for pyrazine, DMP, MDMP, TrMP, and TeMP. While IBMP and IPMP were never detected in 140 source or drinking water samples from across China, pyrazine, DMP, MDMP, TrMP, and TeMP occurred throughout with concentrations of n.d.-62.2 ng/L-aq in source water and n.d.-39.6 ng/L-aq in finished water. IBMP, IPMP, and MDMP were present in two Virginia rivers; MDMP occurred in 18% of the samples with concentrations of n.d.-4.4 ng/L, many of which were above the aqueous odor threshold of 0.043 ng/L MDMP. The removal efficiencies through conventional water treatment were poor, ranging from negative removals to ∼10%. Advanced oxidation water treatment could only remove EMP and TrMP. The widespread presence of earthy-musty-sweet pyrazines in source and drinking waters on two continents, their poor removal during water treatment, and ng/L odor threshold concentrations confirm their potential to be T&O issues for consumers.
Topics: China; Consumer Behavior; Drinking Water; Odorants; Pyrazines; Virginia; Water Pollutants, Chemical
PubMed: 32554269
DOI: 10.1016/j.watres.2020.115971