- 3-substituted N-benzylpyrazine-2-carboxamide derivatives: Synthesis, antimycobacterial and antibacterial evaluation
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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-(3,4-dichlorobenzyl)-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 μ·M. 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.
- Semelková, Lucia,Jand'ourek, Ond?ej,Kone?ná, Klára,Paterová, Pavla,Navrátilová, Lucie,Trejtnar, Franti?ek,Kubí?ek, Vladimír,Kune?, Ji?í,Dole?al, Martin,Zitko, Jan,McPhee, Derek J.
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- Synthesis and biological evaluation of N-alkyl-3-(alkylamino)-pyrazine-2-carboxamides
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A series of N-alkyl-3-(alkylamino)pyrazine-2-carboxamides and their N-alkyl-3-chloropyrazine-2-carboxamide precursors were prepared. All compounds were characterized by analytical methods and tested for antimicrobial and antiviral activity. The antimycobacterial MIC values against Mycobacterium tuberculosis H37Rv of the most effective compounds, 3-(hexylamino)-, 3-(heptylamino)- and 3-(octylamino)-N-methylpyrazine-2-carboxamides 14-16, was 25 μg/mL. The compounds inhibited photosystem 2 photosynthetic electron transport (PET) in spinach chloroplasts. This activity was strongly connected with the lipophilicity of the compounds. For effective PET inhibition longer alkyl chains in the 3-(alkylamino) substituent in the N-alkyl-3-(alkylamino)pyrazine-2-carboxamide molecule were more favourable than two shorter alkyl chains.
- Semelkova, Lucia,Konecna, Klara,Paterova, Pavla,Kubicek, Vladimir,Kunes, Jiri,Novakova, Lucie,Marek, Jan,Naesens, Lieve,Pesko, Matus,Kralova, Katarina,Dolezal, Martin,Zitko, Jan
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- Derivatives of pyrazinecarboxylic acid: 1H, 13C and 15N NMR spectroscopic investigations
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NMR spectroscopic studies are undertaken with derivatives of 2-pyrazinecarboxylic acid. Complete and unambiguous assignment of chemical shifts (1H, 13C, 15N) and coupling constants (1H,1H; 13C,1H; 15N,1H) is achieved by combined application of various 1D and 2D NMR spectroscopic techniques. Unequivocal mapping of13C,1H spin coupling constants is accomplished by 2D (S,J) long-range INEPT spectra with selective excitation. Phenomena such as the tautomerism of 3-hydroxy-2-pyrazinecarboxylic acid are discussed.
- Holzer, Wolfgang,Eller, Gernot A.,Datterl, Barbara,Habicht, Daniela
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scheme or table
p. 617 - 624
(2010/07/05)
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- A New Route to 2,3-Disubstituted Pyrazines; Regioselective Metalation of Chloropyrazine
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Chloropyrazine is regioselectively metalated by lithium amides in tetrahydrofuran to give 3-chloro-2-lithiopyrazine.The reaction of this lithio derivative with electrophiles can either be performed in situ (with the electrophile, e.g., chlorotrimethylsila
- Turck, A.,Mojovic, L.,Queguiner, G.
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p. 881 - 884
(2007/10/02)
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- SYNTHESIS OF 9H-PYRROLO-1,4-DIAZAINDOL-9-ONE
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The synthesis of 9H-pyrrolo-1,4-diazaindol-9-one was achieved either by an intramolecular electrophilic substitution of 2-chlorocarbonyl-3-N-pyrrolopyrazine 7 and 2-N-pyrrolidinocarbonyl-3-N-pyrrolopyrazine 8 or by the intramolecular nucleophilic substitution of 2-chloro-3-(2-pyrrolyl)pyrazine 12.
- Laduree, Daniel,Kashef, Hussein El,Robba, Max
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p. 299 - 301
(2007/10/02)
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