148673-71-6Relevant articles and documents
Substituted amides of pyrazine-2-carboxylic acids: Synthesis and biological activity
Dolezal, Martin,Miletin, Miroslav,Kunes, Jiri,Kralova, Katarina
, p. 363 - 373 (2002)
Condensation of 6-chloro-, 5-tert-butyl- or 6-chloro-5-tert-butylpyrazine- 2-carboxylic acid chloride with ring substituted anilines yielded a series of amides, which were tested for their in vitro antimycobacterial, antifungal and photosynthesis-inhibiting activities. The highest antituberculotic activity (72% inhibition) against Mycobacterium tuberculosis and the highest lipophilicity (log P = 6.85) were shown by the 3,5-bis-trifluoromethylphenyl amide of 5-tert-butyl-6-chloropyrazine-2-carboxylic acid (2o). The 3-methylphenyl amides of 6-chloro- and 5-tert-butyl-6-chloro-pyrazine-2-carboxylic acid (2d and 2f) exhibited only a poor in vitro (antifungal effect (MIC = 31.25-500 μmol·dm-3) against all strains tested, although the latter was the most active antialgal compound (IC50 = 0.063 mmol·dm-3). The most active inhibitor of oxygen evolution rate in spinach chloroplasts was the (3,5-bis-trifluoromethylphenyl)amide of 6-chloropyrazine-2-carboxylic acid (2m, IC50 = 0.026 mmol·dm-3).
Vibrational spectroscopic studies and ab initio calculations of a substituted amide of pyrazine-2-carboxylic acid-C12H10ClN3O
Mary, Y. Sheeena,Varghese, Hema Tresa,Panicker, C. Yohannan,Dolezal, Martin
, p. 725 - 730 (2008)
A substituted amide of pyrazine-2-carboxylic acid was prepared and the IR spectrum is recorded and analysed. The vibrational frequencies and corresponding vibrational assignments are examined theoretically using the Gaussian03 set of quantum chemistry cod
Substituted pyrazinecarboxamides: Synthesis and biological evaluation
Dolezal, Martin,Palek, Lukas,Vinsova, Jarmila,Buchta, Vladimir,Jampilek, Josef,Kralova, Katarina
, p. 242 - 256 (2006)
Condensation of the corresponding chlorides of some substituted pyrazine-2-carboxylic acids (pyrazine-2-carboxylic acid, 6-chloropyrazine-2- carboxylic acid, 5-tertbutylpyrazine-2-carboxylic acid or 5-tert-butyl-6- chloropyrazine-2-carboxylic acid) with various ring-substituted aminothiazoles or anilines yielded a series of amides. The syntheses, analytical and spectroscopic data of thirty newly prepared compounds are presented. Structure-activity relationships between the chemical structures and the antimycobacterial, antifungal and photosynthesis-inhibiting activity of the evaluated compounds are discussed. 3,5-Bromo-4-hydroxyphenyl derivatives of substituted pyrazinecarboxylic acid, 16-18, have shown the highest activity against Mycobacterium tuberculosis H37Rv (54-72% inhibition). The highest antifungal effect against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for 5-tert-butyl-6-chloro-N-(4- methyl-1,3-thiazol-2-yl)pyrazine-2-carboxamide (8, MIC = 31.25 μmol·mL-1). The most active inhibitors of oxygen evolution rate in spinach chloroplasts were the compounds 5-tert-butyl-6-chloro-N-(5- bromo-2-hydroxyphenyl)-pyrazine-2-carboxamide (27, IC50 = 41.9 μmol·L-1) and 5-tert-butyl-6-chloro-N-(1,3-thiazol-2-yl)- pyrazine-2-carboxamide (4, IC50 = 49.5 μmol·L -1).
Synthesis and Antimicrobial Evaluation of 6-Alkylamino-N-phenylpyrazine-2-carboxamides
Servusova-Vanaskova, Barbora,Paterova, Pavla,Garaj, Vladimir,Mandikova, Jana,Kunes, Jiri,Naesens, Lieve,Jílek, Petr,Dolezal, Martin,Zitko, Jan
, p. 674 - 681 (2015)
This work presents synthesis and antimicrobial evaluation of nineteen 6-alkylamino-N-phenylpyrazine-2-carboxamides. Antimycobacterial activity was determined against Mycobacterium tuberculosis H37Rv, M. kansasii and two strains of M. avium. Generally, the antimycobacterial activity increased with prolongation of simple alkyl chain and culminated in compounds with heptylamino substitution (3e, 4e) with MIC = 5-10 μm against M. tuberculosis H37Rv. On the contrary, derivatives with modified alkyl chain (containing e.g. terminal methoxy or hydroxy group) as well as phenylalkylamino derivatives were mainly inactive. The most active compounds (with hexyl to octylamino substitution) were evaluated for their in vitro activity against drug-resistant strains of M. tuberculosis and possessed activity comparable to that of the reference drug isoniazid. None of the tested compounds were active against M. avium. Some derivatives exhibited activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (best MIC = 7.8 μm), while Gram-negative strains as well as tested fungal strains were completely unsusceptible. Active compounds were tested for in vitro toxicity on various cell lines and in most cases were non-toxic up to 100 μm.
Design, synthesis and antimycobacterial activity of hybrid molecules combining pyrazinamide with a 4-phenylthiazol-2-amine scaffold
Zitko, Jan,Jand'Ourek, Ond?ej,Paterová, Pavla,Navrátilová, Lucie,Kune?, Ji?í,Vin?ová, Jarmila,Dole?al, Martin
, p. 685 - 696 (2018)
Hybrid compounds based on a combination of the first-line antitubercular pyrazinamide (PZA) and a formerly identified antimycobacterial scaffold of 4-arylthiazol-2-amine were designed. Eighteen compounds were prepared, characterized and tested for in vitro growth inhibition activity against M. tuberculosis H37Rv, M. kansasii, M. avium and M. smegmatis by Microplate Alamar Blue Assay at neutral pH. Active compounds were tested for in vitro cytotoxicity in the human hepatocellular carcinoma cell line (HepG2). The most active 6-chloro-N-[4-(4-fluorophenyl)thiazol-2-yl]pyrazine-2-carboxamide (9b) also had the broadest spectrum of activity and inhibited M. tuberculosis, M. kansasii, and M. avium with MIC = 0.78 μg mL-1 (2.3 μM) and a selectivity index related to HepG2 cells of SI > 20. Structure-activity relationships within the series are discussed. Based on its structural similarity to known inhibitors and the results of a molecular docking study, we suggest mycobacterial beta-ketoacyl-(acyl-carrier-protein) synthase III (FabH) as a potential target.
Substituted N-phenylpyrazine-2-carboxamides, their synthesis and evaluation as herbicides and abiotic elicitors
Dolezal, Martin,Tumova, Lenka,Kesetovicova, Diana,Tuma, Jiri,Kral'ova, Katarina
, p. 2589 - 2598 (2007)
The condensation of substituted pyrazine-2-carboxylic acid chlorides with ring-substituted anilines yielded five substituted pyrazine-2-carboxylic acid amides. The synthesis, and analytical, lipophilicity and biological data of the newly synthesized compo
SUBSTITUTED 2,4-DIHYDRO-3H-1,2,4-TRIAZOL-3-ONES AND USE OF SAME
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Paragraph 0614-0615, (2020/12/13)
The invention relates to prolyl endopeptidase (PREP) inhibitors which contain a condensed 2,4-dihydro-3H-1,2,4-triazol-3-one ring system, methods for producing same, the use thereof alone or in combinations for treating and/or preventing diseases, and the
Synthesis and in vitro evaluation of diverse heterocyclic diphenolic compounds as inhibitors of DYRK1A
Zhou, Qingqing,Reekie, Tristan A.,Abbassi, Ramzi H.,Indurthi Venkata, Dinesh,Font, Josep S.,Ryan, Renae M.,Munoz, Lenka,Kassiou, Michael
, p. 5852 - 5869 (2018/11/10)
Dual-specificity tyrosine phosphorylation-related kinase 1A (DYRK1A) is a dual-specificity protein kinase that catalyses phosphorylation and autophosphorylation. Higher DYRK1A expression correlates with cancer, in particular glioblastoma present within the brain. We report here the synthesis and biological evaluation of new heterocyclic diphenolic derivatives designed as novel DYRK1A inhibitors. The generation of these heterocycles such as benzimidazole, imidazole, naphthyridine, pyrazole-pyridines, bipyridine, and triazolopyrazines was made based on the structural modification of the lead DANDY and tested for their ability to inhibit DYRK1A. None of these derivatives showed significant DYRK1A inhibition but provide valuable knowledge around the importance of the 7-azaindole moiety. These data will be of use for developing further structure-activity relationship studies to improve the selective inhibition of DYRK1A.
Design, synthesis and anti-mycobacterial evaluation of some new N-phenylpyrazine-2-carboxamides
Zitko, Jan,Barbora, Servusova-Vanaskova,Paterova, Pavla,Navratilova, Lucie,Trejtnar, Frantisek,Kunes, Jiri,Dolezal, Martin
, p. 649 - 657 (2016/03/05)
N-Phenylpyrazine-2-carboxamides (anilides of pyrazinoic acids with simple substituents in various positions) were previously shown to possess significant biological activities in vitro, markedly anti-mycobacterial and photosynthesis-inhibiting activity. Based on structure-activity relationships (SAR) extracted from previously published series, 25 new anilides of non-substituted pyrazinoic acid (POA), 5-CH3-POA, 6-Cl-POA, 5-tert-butyl-POA and 5-tert-butyl-6-Cl-POA were designed and synthesised. The phenyl part was substituted with simple hydrophobic substituents chosen from methyl and halogens. 5-tert-Butyl-N-(5-fluoro-2-methylphenyl)pyrazine-2-carboxamide (9), N-(3-chloro-4-methylphenyl)-5-methylpyrazine-2-carboxamide (12), 6-chloro-N-(3-chloro-4-methylphenyl)pyrazine-2-carboxamide (13) and 6-chloro-N-(5-iodo-2-methylphenyl)pyrazine-2-carboxamide (18) possessed whole cell anti-mycobacterial activity in vitro against Mycobacterium tuberculosis H37Rv with minimum inhibitory concentration (MIC) of around 10 μM. Importantly, no cytotoxicity in the HepG2 model was detected in vitro at the concentrations tested and the estimated IC50 values were in hundreds of μM, indicating promising selectivity. N-(3-Chloro-4-methylphenyl)pyrazine-2-carboxamide (11) and N-(4-chloro-2-iodophenyl)pyrazine-2-carboxamide (21) exerted significant activity against Mycobacterium kansasii with MIC 12.6 μM and 8.7 μM, respectively. No activity was detected against Mycobacterium avium. SAR were in accordance with those observed for the derivatives previously published.
Alkylamino derivatives of N-benzylpyrazine-2-carboxamide: synthesis and antimycobacterial evaluation
Servusova-Vanaskova, Barbora,Jandourek, Ondrej,Paterova, Pavla,Kordulakova, Jana,Plevakova, Magdalena,Kubicek, Vladimir,Kucera, Radim,Garaj, Vladimir,Naesens, Lieve,Kunes, Jiri,Dolezal, Martin,Zitko, Jan
supporting information, p. 1311 - 1317 (2015/07/15)
A series of alkylamino derivatives of N-benzylpyrazine-2-carboxamide was designed, synthesized and assayed in vitro for their antimycobacterial, antibacterial, antifungal as well as antiviral activities. Final structures were prepared from 6-chloro (1), 5-chloro (2) or 3-chloro (3) derivatives of N-benzylpyrazine-2-carboxamide by nucleophilic substitution of chlorine with n-alkylamines in the range from butylamine to octylamine (labelled a-e). Series 1a-e and 2a-e exerted higher activity against Mycobacterium tuberculosis H37Rv compared to the corresponding pattern compounds and the reference compound pyrazinamide. The most active derivatives reached an activity MIC = 4.6-10 μM (M. tbc H37Rv). More importantly, activity was also observed against other tested mycobacterial strains (including drug-resistant strains). Substitution of 3-chlorine was disadvantageous and led to completely inactive compounds 3a-e. Some compounds showed activity against Gram-positive bacterial strains (including MRSA) or influenza virus, but no antifungal activity was observed.
