N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological Properties (original) (raw)
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2014
In this work a series of 15 N-benzylamine substituted 5-amino-6-methylpyrazine-2,3-dicarbonitriles was prepared by the aminodehalogenation reactions using microwave assisted synthesis with experimentally set and proven conditions. This approach for the aminodehalogenation reaction was chosen due to its higher yields and shorter reaction times. The products of this reaction were characterized by IR, NMR and other analytical data. The compounds were evaluated for their antibacterial, antifungal and herbicidal activity. Compounds 3 (R = 3,4-Cl), 9 (R = 2-Cl) and 11 (R = 4-CF 3) showed good antimycobacterial activity against Mycobacterium tuberculosis (MIC = 6.25 µg/mL). It was found that the lipophilicity is important for antimycobacterial activity and the best
Synthesis and antimycobacterial properties of N-substituted 6-amino-5-cyanopyrazine-2-carboxamides
Bioorganic & Medicinal Chemistry, 2011
A series of fifteen new compounds related to pyrazinamide (PZA) were synthesized, characterized with analytical data and screened for antimycobacterial, antifungal and antibacterial activity. The series consists of 6-chloro-5-cyanopyrazine-2-carboxamide and N-substituted 6-amino-5-cyanopyrazine-2carboxamides, derived from the previous by nucleophilic substitution with various non-aromatic amines (alkylamines, cycloalkylamines, heterocyclic amines). Some of the compounds exerted antimycobacterial activity against Mycobacterium tuberculosis equal to pyrazinamide (12.5-25 lg/mL). More importantly, 6-chloro-5-cyanopyrazine-2-carboxamide and 5-cyano-6-(heptylamino)pyrazine-2-carboxamide were active against Mycobacterium kansasii and Mycobacterium avium, which are unsusceptible to PZA. Basic structure-activity relationships are presented. Only weak antifungal and no antibacterial activity was detected.
Journal of Heterocyclic Chemistry, 2018
In the present investigation, a series of 4-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)benzenamine analogs 6a-o were synthesized and characterized by IR, NMR (1 H and 13 C), and mass spectra. All newly synthesized compounds 6a-o were prepared under conventional and microwave irradiation methods. These compounds obtained in higher yields and in shorter reaction times in the microwave irradiation method when compared with the conventional method. Synthesized compounds 6a-o were inspected for their in vitro antitubercular activity against Mycobacterium tuberculosis H 37 Ra using an established XTT reduction menadione assay. Among the screened compounds, 6i (IC 50 : 1.82 μg/mL), 6j (IC 50 : 1.02 μg/mL), and 6k (IC 50 : 1.59 μg/mL) showed excellent activity. Furthermore, compound 6i showed MIC 90 value of 16.02 μg/mL. In summary, the results indicate the identification of some novel, selective, and specific inhibitors against M. tuberculosis that can be explored further for the potential antitubercular drug.
Molecules
A series of substituted N-benzyl-3-chloropyrazine-2-carboxamides were prepared as positional isomers of 5-chloro and 6-chloro derivatives, prepared previously. During the aminolysis of the acyl chloride, the simultaneous substitution of chlorine with benzylamino moiety gave rise to N-benzyl-3-(benzylamino)pyrazine-2-carboxamides as side products, in some cases. Although not initially planned, the reaction conditions were modified to populate this double substituted series. The final compounds were tested against four mycobacterial strains. N-(2-methylbenzyl)-3-((2-methylbenzyl)amino)pyrazine-2-carboxamide (1a) and N-(3,4dichlorobenzyl)-3-((3,4-dichlorobenzyl)amino)pyrazine-2-carboxamide (9a) proved to be the most effective against Mycobacterium tuberculosis H37Rv, with MIC = 12.5 µg•mL −1. Compounds were screened for antibacterial activity. The most active compound was 3-chloro-N-(2-chlorobenzyl) pyrazine-2-carboxamide (5) against Staphylococcus aureus with MIC = 7.81 µM, and Staphylococcus epidermidis with MIC = 15.62 µM. HepG2 in vitro cytotoxicity was evaluated for the most active compounds; however, no significant toxicity was detected. Compound 9a was docked to several conformations of the enoyl-ACP-reductase of Mycobacterium tuberculosis. In some cases, it was capable of H-bond interactions, typical for most of the known inhibitors.
2018
N'-[-1-phenylethylidene] pyridine-4-carbohydrazide (3a-f) were prepared by reacting with substituted acetophenone and iso-nicotinic acid hydrazide and were reacted with Phosphorous oxy chloride and Dimethyl formamide to yield 3-phenyl-1-(pyridin-4-ylcarbonyl)-1H-pyrazole-4-carbaldehyde (4a-f). Solution of substituted acetophenone and Pyrazole-4-carbaldehyde were reacted to obtain 1-phenyl-3-[3phenyl-1-(pyridin-4-ylcarbonyl)-1H-pyrazol-4-yl] prop-2-en-1-one (5a-f). To Synthesize 5, 3'-diphenyl-1', 2-diisonicotinoyl-3, 4-dihydro-1'H, 2H-3, 4'-bipyrazole (6a-f), 1-phenyl-3-[3-phenyl-1-(pyridin-4ylcarbonyl)-1H-pyrazol-4-yl] prop-2-en-1-one was reacted with iso-nicotinic acid hydrazide. Moreover, the compounds revealed antimicrobial activity together with significant antifungal activities to some extent. Compound 6f with methoxy substitution, was found to be the most potent compound of the series with antifungal activity comparable to the standard drug, Fluconazole, a...
Bioorganic & Medicinal Chemistry Letters, 2009
a b s t r a c t 2- [1]indoloacetyl)-3-(1-benzofuran-2-yl)-4,5-dihydro-1H-pyrazol-5-yl] phenyl derivatives were synthesized from 2- (5,8-dihydro quinoxalino[2,3-b]indol-5-yl) acetohydrazide and (2E)-1-(1-benzofuran-2-yl)-4-phenylbut-2-en-1-ones derivatives using microwave-assisted route. The structures of all the compounds have been established on the basis of analytical and spectral data. Among the 14 compounds IPB-1, IPB-5, IPB-10, IPB-11 and IPB-12 were found good antibacterial activity and MICs were found bellow 10 lg/mL against Escherichia coli, Pseudomonas aeruginosa and Streptococcus aureus, which can compared with sparfloxacin and norfloxacin.
Chemical science transactions, 2012
Synthesis of series of [benzo-(5,6-e)-1,3-diphenyl-2-arylimino-[1,3]-diazepine]-4,7-dione hydrochlorides have been achieved by the interaction of N,N-diphenyl phthalamide with N-aryl isocyanodichlorides by irradiation in a domestic microwave oven for specified time using little chloroform as a solvent along with potassium carbonate. The hydrochlorides were then basified with dilute ammonium hydroxide solution. The parent compound N,N-diphenyl phthalamide was obtained by refluxing the mixture of phthalic anhydride and aniline in toluene. The structures of synthesized compounds were established on the basis of chemical transformation, elemental analysis, IR, 1 H NMR and Mass spectral studies. The synthesized compounds have been assayed for their antimicrobial activity against gram-positive as well as gram-negative microorganisms.