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Molecules 2014, 19(1), 651-671; doi:10.3390/molecules19010651
Article

N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological Properties

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Received: 2 December 2013; in revised form: 29 December 2013 / Accepted: 31 December 2013 / Published: 7 January 2014
(This article belongs to the Section Medicinal Chemistry)
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Abstract: In this work a series of 15 N-benzylamine substituted 5-amino-6-methyl-pyrazine-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-CF3) 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 substitution on the benzyl moiety of the compounds is a halogen or trifluoromethyl group according to Craig’s plot. The activities against bacteria or fungi were insignificant. The presented compounds also inhibited photosynthetic electron transport in spinach chloroplasts and the IC50 values of the active compounds varied in the range from 16.4 to 487.0 µmol/L. The most active substances were 2 (R = 3-CF3), 3 (R = 3,4-Cl) and 11 (R = 4-CF3). A linear dependence between lipophilicity and herbicidal activity was observed.
Keywords: pyrazinamide derivatives; in vitro biological evaluation; microwave-assisted synthesis; tuberculosis; lipophilicity pyrazinamide derivatives; in vitro biological evaluation; microwave-assisted synthesis; tuberculosis; lipophilicity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Jandourek, O.; Dolezal, M.; Paterova, P.; Kubicek, V.; Pesko, M.; Kunes, J.; Coffey, A.; Guo, J.; Kralova, K. N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological Properties. Molecules 2014, 19, 651-671.

AMA Style

Jandourek O, Dolezal M, Paterova P, Kubicek V, Pesko M, Kunes J, Coffey A, Guo J, Kralova K. N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological Properties. Molecules. 2014; 19(1):651-671.

Chicago/Turabian Style

Jandourek, Ondrej; Dolezal, Martin; Paterova, Pavla; Kubicek, Vladimir; Pesko, Matus; Kunes, Jiri; Coffey, Aidan; Guo, Jiahui; Kralova, Katarina. 2014. "N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological Properties." Molecules 19, no. 1: 651-671.


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