Substituted N-Benzylpyrazine-2-carboxamides: Synthesis and Biological Evaluation †

A series of twelve amides was synthesized via aminolysis of substituted pyrazinecarboxylic acid chlorides with substituted benzylamines. Compounds were characterized with analytical data and assayed in vitro for their antimycobacterial, antifungal, antibacterial and photosynthesis-inhibiting activity. 5-tert-Butyl-6-chloro-N-(4-methoxybenzyl)pyrazine-2-carboxamide (12) has shown the highest antimycobacterial activity against Mycobacterium tuberculosis (MIC = 6.25 µg/mL), as well as against other mycobacterial strains. The highest antifungal activity against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for 5-chloro-N-(3-trifluoromethylbenzyl)-pyrazine-2-carboxamide (2, MIC = 15.62 µmol/L). None of the studied compounds exhibited any activity against the tested bacterial strains. Except for 5-tert-butyl-6-chloro-N-benzylpyrazine-2-carboxamide (9, IC50 = 7.4 µmol/L) and 5-tert-butyl-6-chloro-N-(4-chlorobenzyl)pyrazine-2-carboxamide (11, IC50 = 13.4 µmol/L), only moderate or weak photosynthesis-inhibiting activity in spinach chloroplasts (Spinacia oleracea L.) was detected.

• Publication year

  2012

• Venue

  Molecules

• Publication date

  2012-11-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.3390/molecules171113183PMID 23132136PMCID 6268022
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Antimycobacterial evaluation of pyrazinoic acid reversible derivatives.

  2011cited by this paper
• Pyrazinamide, but not pyrazinoic acid, is a competitive inhibitor of NADPH binding to Mycobacterium tuberculosis fatty acid synthase I.

  2011cited by this paper
• Pirazinamida: Um Fármaco Essencial no Tratamento da Tuberculose

  2011cited by this paper
• Synthesis and Evaluation of Pyrazine Derivatives with Herbicidal Activity

  2011cited by this paper
• Synthesis and antimycobacterial properties of N-substituted 6-amino-5-cyanopyrazine-2-carboxamides.

  2011cited by this paper
• Pyrazinamide Inhibits Trans-Translation in Mycobacterium tuberculosis

  2011cited by this paper
• Synthesis, Antimycobacterial, Antifungal and Photosynthesis-Inhibiting Activity of Chlorinated N-phenylpyrazine-2-carboxamides †

  2010cited by this paper
• Synthesis and antimycobacterial evaluation of substituted pyrazinecarboxamides.

  2008cited by this paper
• Inhibition of Isolated Mycobacterium tuberculosis Fatty Acid Synthase I by Pyrazinamide Analogs

  2007cited by this paper
• Substituted N-phenylpyrazine-2-carboxamides, their synthesis and evaluation as herbicides and abiotic elicitors.

  2007cited by this paper
• Pyrazinoic Acid and Its n-Propyl Ester Inhibit Fatty Acid Synthase Type I in Replicating Tubercle Bacilli

  2006cited by this paper
• 5-(3-Bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine: structure-activity relationships of 7-substituted heteroaryl analogs as non-nucleoside adenosine kinase inhibitors.

  2005cited by this paper
• Approaches to Measuring Plant Photosynthetic Activity

  2005influential reference
• The curious characteristics of pyrazinamide: a review.

  2003cited by this paper
• Mode of action of pyrazinamide: disruption of Mycobacterium tuberculosis membrane transport and energetics by pyrazinoic acid.

  2003cited by this paper
• Substituted 5-aroylpyrazine-2-carboxylic acid derivatives: synthesis and biological activity.

  2003cited by this paper
• Effects of Pyrazinamide on Fatty Acid Synthesis by Whole Mycobacterial Cells and Purified Fatty Acid Synthase I

  2002cited by this paper
• Pyrazinamide inhibits the eukaryotic-like fatty acid synthetase I (FASI) of Mycobacterium tuberculosis

  2000cited by this paper
• Inhibitory Effects of Substituted Benzanilides on Photosynthetic Electron Transport in Spinach Chloroplasts.

  2000cited by this paper
• Synthesis and Photosynthesis‐Inhibiting Activity of Some Anilides of Substituted Pyrazine‐2‐carboxylic Acids.

  1999cited by this paper
• Effect of Mycobacterium tuberculosis on HIV replication. Role of immune activation.

  1996cited by this paper
• Mutations in pncA, a gene encoding pyrazinamidase/nicotinamidase, cause resistance to the antituberculous drug pyrazinamide in tubercle bacillus

  1996influential reference
• Sixty-Three Years Since Kautsky: Chlorophyll a Fluorescence

  1995cited by this paper
• Optimal dilution susceptibility testing conditions, recommendations for MIC interpretation, and quality control guidelines for the ampicillin-sulbactam combination

  1987cited by this paper
• Biochemistry and Physiology of Herbicide Action

  1982cited by this paper
• Pyrazinamide susceptibility and amidase activity of tubercle bacilli.

  1967influential reference

• Design, Synthesis, Antibacterial Activity, and Mechanism of Action of Coumarin Derivatives Containing Benzylamine

  2025cites this paper
• Pyrazine derivative synthesis in a continuous-flow system: a green synthesis of pyrazinamide from pyrazine esters and amines catalyzed by Lipozyme® TL IM from Thermomyces lanuginosus

  2024cites this paper
• Antibacterial Activity and Mechanism of Action of New Benzylamine-Containing Coumarin Derivatives

  2024cites this paper
• Effects of Novel Photosynthetic Inhibitor [CuL2]Br2 Complex on Photosystem II Activity in Spinach

  2022influential citation
• Pyrazinamide Analogs Designed for Rational Drug Designing Strategies against Resistant Tuberculosis

  2022cites this paper
• Characterization and applications of Thermomonas hydrothermalis isolated from Jordan's hot springs for biotechnological and medical purposes

  2021cites this paper
• Synthesis and molecular docking study of 6-chloropyrazine-2-carboxylic acid derivatives

  2020cites this paper
• Concentration of metabolites from Phoma sp. using microfiltration membrane for increasing bioherbicidal activity

  2019cites this paper
• Development of new antituberculosis drugs among of 1,3- and 1,4-diazines. Highlights and perspectives

  2019cites this paper
• Zlúčeniny kombinujúce fragment pyrazínamidu a 4-aminobenzoovej kyseliny ako potencionálne antituberkulotiká

  2018cites this paper
• Design, synthesis and antimycobacterial activity of hybrid molecules combining pyrazinamide with a 4-phenylthiazol-2-amine scaffold.

  2018cites this paper
• Antimycobacterial N-alkoxyphenylhydroxynaphthalenecarboxamides affecting photosystem II.

  2017cites this paper
• 3-Substituted N-Benzylpyrazine-2-carboxamide Derivatives: Synthesis, Antimycobacterial and Antibacterial Evaluation

  2017influential citation
• Chapter 7 References

  2017cites this paper
• Synthesis of Novel Pyrazinamide Derivatives Based on 3-Chloropyrazine-2-carboxamide and Their Antimicrobial Evaluation

  2017cites this paper
• Halogenated 1-Hydroxynaphthalene-2-Carboxanilides Affecting Photosynthetic Electron Transport in Photosystem II

  2017cites this paper
• Synthesis and Antifungal Screening of 2-{[1-(5-Alkyl/arylalkylpyrazin-2-yl)ethylidene]hydrazono}-1,3-thiazolidin-4-ones †

  2016cites this paper
• New Synthetic Pyrazine Carboxamide Derivatives as Potential Elicitors in Production of Secondary Metabolite in In vitro Cultures

  2016cites this paper
• Ring-substituted 8-hydroxyquinoline-2-carboxanilides as photosystem II inhibitors.

  2016cites this paper
• Alkylamino derivatives of N-benzylpyrazine-2-carboxamide: synthesis and antimycobacterial evaluation

  2015cites this paper
• Synthesis and Biological Evaluation of N-Alkoxyphenyl-3-hydroxynaphthalene-2-carboxanilides

  2015cites this paper
• Synthesis and Biological Evaluation of N-Alkyl-3-(alkylamino)-pyrazine-2-carboxamides

  2015cites this paper
• Synthesis, antimycobacterial and antifungal evaluation of some new 1-ethyl-5-(hetero)aryl-6-styryl-1,6-dihydropyrazine-2,3-dicarbonitriles.

  2015cites this paper
• Synthesis and biological evaluation of T-OA analogues as the cytotoxic agents

  2015cites this paper
• Design, synthesis and anti-mycobacterial evaluation of some new N-phenylpyrazine-2-carboxamides

  2015cites this paper
• A REVIEW OF BIOLOGICAL POTENTIAL OF PYRAZINE AND RELATED HETEROCYCLIC COMPOUNDS

  2014cites this paper
• Functional tetranuclear square grids synthesized by in situ oxidation of ligand

  2014cites this paper
• New Potentially Active Pyrazinamide Derivatives Synthesized Under Microwave Conditions

  2014cites this paper
• Synthesis and Antimycobacterial and Photosynthesis-Inhibiting Evaluation of 2-[(E)-2-Substituted-ethenyl]-1,3-benzoxazoles

  2014cites this paper
• Amino Acid Derivatives of Ligustrazine-Oleanolic Acid as New Cytotoxic Agents

  2014cites this paper
• N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological Properties

  2014cites this paper
• Interactions with selected drug renal transporters and transporter-mediated cytotoxicity in antiviral agents from the group of acyclic nucleoside phosphonates.

  2013cites this paper
• Synthesis, Antimycobacterial Activity and In Vitro Cytotoxicity of 5-Chloro-N-phenylpyrazine-2-carboxamides

  2013cites this paper
• 5-Bromo- and 3,5-dibromo-2-hydroxy-N-phenylbenzamides — inhibitors of photosynthesis

  2013cites this paper
• Antimycobacterial and Photosynthetic Electron Transport Inhibiting Activity of Ring-Substituted 4-Arylamino-7-Chloroquinolinium Chlorides

  2013cites this paper
• Antibacterial and Herbicidal Activity of Ring-Substituted 2-Hydroxynaphthalene-1-carboxanilides

  2013cites this paper
• Synthesis and antimycobacterial evaluation of N-substituted 5-chloropyrazine-2-carboxamides.

  2013cites this paper