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Molecules (Basel, Switzerland) Nov 2023Pyrazine is a six-membered heterocyclic ring containing nitrogen, and many of its derivatives are biologically active compounds. References have been downloaded through... (Review)
Review
Pyrazine is a six-membered heterocyclic ring containing nitrogen, and many of its derivatives are biologically active compounds. References have been downloaded through Web of Science, PubMed, Science Direct, and SciFinder Scholar. The structure, biological activity, and mechanism of natural product derivatives containing pyrazine fragments reported from 2000 to September 2023 were reviewed. Publications reporting only the chemistry of pyrazine derivatives are beyond the scope of this review and have not been included. The results of research work show that pyrazine-modified natural product derivatives have a wide range of biological activities, including anti-inflammatory, anticancer, antibacterial, antiparasitic, and antioxidant activities. Many of these derivatives exhibit stronger pharmacodynamic activity and less toxicity than their parent compounds. This review has a certain reference value for the development of heterocyclic compounds, especially pyrazine natural product derivatives.
Topics: Pyrazines; Chemistry, Pharmaceutical; Anti-Inflammatory Agents; Anti-Bacterial Agents; Biological Products
PubMed: 37959859
DOI: 10.3390/molecules28217440 -
Expert Review of Clinical Pharmacology Sep 2019: The receptor tyrosine kinase is the most commonly mutated gene in acute myeloid leukemia (AML). -internal tandem duplication mutations are associated with an... (Review)
Review
: The receptor tyrosine kinase is the most commonly mutated gene in acute myeloid leukemia (AML). -internal tandem duplication mutations are associated with an increased risk of relapse, and a number of small molecule inhibitors of FLT3 have been developed. The highly potent and selective FLT3 kinase inhibitor gilteritinib is the first tyrosine kinase inhibitor approved as monotherapy for the treatment of relapsed and/or refractory -mutated AML. : We review the biology and prognostic significance of mutations in AML and discuss the pharmacology, clinical efficacy, and toxicity profile of gilteritinib. We also summarize important differences among the various FLT3 inhibitors that are currently approved or under development and highlight areas of ongoing research. : Gilteritinib has been shown to improve survival compared to salvage chemotherapy in relapsed and/or refractory -mutated AML. Gilteritinib is orally available with a favorable toxicity profile and as such is quickly becoming the standard of care for this patient population. Ongoing clinical trials are evaluating gilteritinib in combination with frontline chemotherapy, in combination with other agents such as venetoclax and azacitidine for patients who are ineligible for standard induction therapy, and as a maintenance agent.
Topics: Aniline Compounds; Antineoplastic Agents; Humans; Leukemia, Myeloid, Acute; Mutation; Prognosis; Protein Kinase Inhibitors; Pyrazines; Recurrence; Survival; fms-Like Tyrosine Kinase 3
PubMed: 31454267
DOI: 10.1080/17512433.2019.1657009 -
Expert Review of Anti-infective Therapy Apr 2022The role of favipiravir (FVP) as a COVID-19 treatment is recognized but not fully elucidated. We aimed to evaluate whether FVP has definite clinical efficacy and safety... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of favipiravir (FVP) as a COVID-19 treatment is recognized but not fully elucidated. We aimed to evaluate whether FVP has definite clinical efficacy and safety in the treatment of COVID-19.
METHODS
International and Chinese databases were searched for randomized controlled clinical trials evaluating FVP for the treatment of COVID-19. A meta-analysis was performed and published literature was synthesized to evaluate the corresponding therapeutic effects.
RESULTS
We included 13 studies (1430 patients in total). Meta-analysis showed that patients with mild-to-moderate disease treated with FVP had a significantly higher viral clearance rate than those in the control group 10 and 14 days after initiation of treatment [RR: 1.13 (95% CI: 1.00, 1.28), P = 0.04; I = 39% for day 10 and RR: 1.16 (95% CI: 1.04, 1.30), P = 0.008; I = 38% for day 14] and a significantly shorter hospital stay [MD: -1.52 (95% CI: -2.82, -0.23), P = 0.02; I = 0%].
CONCLUSIONS
FVP significantly promotes viral clearance and reduces the hospitalization duration in mild-to-moderate COVID-19 patients, which can reduce the risk of severe disease outcomes in patients. However, more importantly, the results showed no benefit of FVP in severe patients, and caution should be taken regarding the treatment options of FVP in severe patients.
Topics: Amides; Humans; Pyrazines; Randomized Controlled Trials as Topic; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34846960
DOI: 10.1080/14787210.2022.2012155 -
Molecules (Basel, Switzerland) May 2020The incorporation of the trifluoromethoxy group into organic molecules has become very popular due to the unique properties of the named substituent that has a...
The incorporation of the trifluoromethoxy group into organic molecules has become very popular due to the unique properties of the named substituent that has a "pseudohalogen" character, while the chemical properties of the synthesized compound, especially heterocycles with such a group, are less studied. As trifluoromethoxy-substituted pyrazines are still unknown, we have developed efficient and scalable methods for 2-chloro-5-trifluoromethoxypyrazine synthesis, showing the synthetic utility of this molecule for Buchwald-Hartwig amination and the Kumada-Corriu and Suzuki and Sonogashira coupling reactions. Some comparisons of chlorine atom and trifluoromethoxy group stability in these transformations have been carried out.
Topics: Amination; Halogenation; Molecular Structure; Proton Magnetic Resonance Spectroscopy; Pyrazines
PubMed: 32397388
DOI: 10.3390/molecules25092226 -
Expert Review of Anti-infective Therapy Aug 2021At this time, there is no specific therapeutic or vaccine for treatment of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, available drugs for... (Review)
Review
INTRODUCTION
At this time, there is no specific therapeutic or vaccine for treatment of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Hence, available drugs for treatment of other viral infections may be useful to treat COVID-19.
AREAS COVERED
The focus of the current review was studying the main characteristics of favipiravir and its usefulness to treat COVID-19. An electronic search was done by using Pubmed and Google scholar.
EXPERT OPINION
Based on the mechanism of action and safety of favipiravir, the drug may be a promising candidate for compassionate use against the SARS-CoV-2 infection. Favipiravir has a wide range of activity against many single-stranded RNA viruses, is well tolerated in humans and has a high barrier to resistance. However, high doses of the agent are necessary to obtain an efficient antiviral activity. Favipiravir is teratogen in pregnant women and associated with the hyperuricemia. Therefore, the administration of the drug should be well controlled. Investigating the antiviral prophylactic potency of favipiravir and search for its pro-drugs and/or analogs showing improved activity and/or safety are critical.
Topics: Adult; Amides; Antiviral Agents; Female; Humans; Pregnancy; Pyrazines; COVID-19 Drug Treatment
PubMed: 33372567
DOI: 10.1080/14787210.2021.1866545 -
Pharmacology & Therapeutics Jun 2020Chemoresistance, radioresistance, and the challenge of achieving complete resection are major driving forces in the search for more robust and targeted anticancer... (Review)
Review
Chemoresistance, radioresistance, and the challenge of achieving complete resection are major driving forces in the search for more robust and targeted anticancer therapies. Targeting the DNA damage response has recently attracted research interest, as these processes are enhanced in tumour cells. The major replication stress responder is ATM and Rad3-related (ATR) kinase, which is attracting attention worldwide with four drug candidates currently in phase I/II clinical trials. This review addresses a potent and selective small-molecule ATR inhibitor, which is known as VX-970 (also known as berzosertib or M6620), and summarizes the existing preclinical data to provide deep insight regarding its real potential. We also outline the transition from preclinical to clinical studies, as well as its relationships with other clinical candidates (AZD6738, VX-803 [M4344], and BAY1895344). The results suggest that VX-970 is indeed a promising anticancer drug that can be used both as monotherapy and in combination with either chemotherapy or radiotherapy strategies. Based on patient anamnesis and biomarker identification, VX-970 could become a valuable tool for oncologists in the fight against cancer.
Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Ataxia Telangiectasia Mutated Proteins; Drug Discovery; Drug Synergism; Humans; Isoxazoles; Molecular Targeted Therapy; Neoplasms; Protein Kinase Inhibitors; Pyrazines; Signal Transduction; Sulfones; Treatment Outcome
PubMed: 32109490
DOI: 10.1016/j.pharmthera.2020.107518 -
Expert Review of Respiratory Medicine May 2021: Pulmonary arterial hypertension (PAH) is a rare pulmonary vasculopathy. This review focuses on selexipag, a prostacyclin receptor agonist validated for the treatment... (Review)
Review
INTRODUCTION
: Pulmonary arterial hypertension (PAH) is a rare pulmonary vasculopathy. This review focuses on selexipag, a prostacyclin receptor agonist validated for the treatment of PAH.
AREAS COVERED
We review the structure, mechanisms of action, pharmacokinetics, and pharmacodynamics of selexipag. Clinical efficacy and tolerability are discussed using the main clinical trial published for selexipag (GRIPHON) and its post-hoc analysis.
EXPERT OPINION
Selexipag should be added as a triple oral combination therapy in case of insufficient response to oral combination therapy with endothelin receptor antagonist and phosphodiesterase 5 inhibitor. However, selexipag should not replace parenteral prostacyclin in high-risk patients.
Topics: Acetamides; Administration, Oral; Antihypertensive Agents; Humans; Pulmonary Arterial Hypertension; Pyrazines
PubMed: 33382345
DOI: 10.1080/17476348.2021.1866990 -
Bioscience, Biotechnology, and... Oct 2022The relationship between volatile compounds of vinegar and microorganisms is not clear, especially pyrazine, a trace component. In order to reveal their potential...
The relationship between volatile compounds of vinegar and microorganisms is not clear, especially pyrazine, a trace component. In order to reveal their potential relationship, high throughput sequencing, solid-phase microextraction-gas chromatography-mass spectrometry (SPME-GC-MS) and Spearman's correlation analysis were used. Results showed that Acetobacter and Lactobacillus with opposite abundance trends were the predominant bacteria, and the total abundance of them exceeds 98%, while the predominant fungal genera were Aspergillus and Malassezia, their highest abundances are 75.4% and 81.5%, respectively. In the whole process of microbial community succession, 6 pyrazines were detected including trimethylpyrazine and tetramethylpyrazine, etc., and Spearman's correlation analysis showed that they were positively correlated with the presence of Vibrionimonas, Paraburkholderia, Paucibacter, Komagataeibacter, Acinetobacter, and Slinibacter. In general, this study further revealed more species related to pyrazines, it will be helpful to understand the formation of pyrazines and promote the improvement of vinegar quality.
Topics: Acetic Acid; Fermentation; Microbiota; Gas Chromatography-Mass Spectrometry; Pyrazines
PubMed: 35998319
DOI: 10.1093/bbb/zbac143 -
Proceedings of the National Academy of... Sep 2019Marine polychaetes , commonly known as fireworms, emit bright blue-green bioluminescence. Until the recent identification of the luciferase enzyme, little progress had...
Marine polychaetes , commonly known as fireworms, emit bright blue-green bioluminescence. Until the recent identification of the luciferase enzyme, little progress had been made toward characterizing the key components of this bioluminescence system. Here we present the biomolecular mechanisms of enzymatic (leading to light emission) and nonenzymatic (dark) oxidation pathways of newly described luciferin. Spectral studies, including 1D and 2D NMR spectroscopy, mass spectrometry, and X-ray diffraction, of isolated substances allowed us to characterize the luciferin as an unusual tricyclic sulfur-containing heterocycle. luciferin does not share structural similarity with any other known luciferins. The structures of the bioluminescent system's low molecular weight components have enabled us to propose chemical transformation pathways for the enzymatic and nonspecific oxidation of luciferin.
Topics: Animals; Biosynthetic Pathways; Color; Indoles; Luminescent Agents; Luminescent Measurements; Luminescent Proteins; Molecular Structure; Oxidation-Reduction; Polychaeta; Pyrazines
PubMed: 31462497
DOI: 10.1073/pnas.1902095116 -
Nature Mar 2023Pyridines and related N-heteroarenes are commonly found in pharmaceuticals, agrochemicals and other biologically active compounds. Site-selective C-H functionalization...
Pyridines and related N-heteroarenes are commonly found in pharmaceuticals, agrochemicals and other biologically active compounds. Site-selective C-H functionalization would provide a direct way of making these medicinally active products. For example, nicotinic acid derivatives could be made by C-H carboxylation, but this remains an elusive transformation. Here we describe the development of an electrochemical strategy for the direct carboxylation of pyridines using CO. The choice of the electrolysis setup gives rise to divergent site selectivity: a divided electrochemical cell leads to C5 carboxylation, whereas an undivided cell promotes C4 carboxylation. The undivided-cell reaction is proposed to operate through a paired-electrolysis mechanism, in which both cathodic and anodic events play critical roles in altering the site selectivity. Specifically, anodically generated iodine preferentially reacts with a key radical anion intermediate in the C4-carboxylation pathway through hydrogen-atom transfer, thus diverting the reaction selectivity by means of the Curtin-Hammett principle. The scope of the transformation was expanded to a wide range of N-heteroarenes, including bipyridines and terpyridines, pyrimidines, pyrazines and quinolines.
Topics: Hydrogen; Pyrazines; Pyridines; Pyrimidines; Electrochemistry; Carbon Dioxide; Quinolines; Pharmaceutical Preparations
PubMed: 36603811
DOI: 10.1038/s41586-022-05667-0