N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological Properties
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...
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MDPI AG
2014-01-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/19/1/651 |
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| author | Ondrej Jandourek Martin Dolezal Pavla Paterova Vladimir Kubicek Matus Pesko Jiri Kunes Aidan Coffey Jiahui Guo Katarina Kralova |
| author_facet | Ondrej Jandourek Martin Dolezal Pavla Paterova Vladimir Kubicek Matus Pesko Jiri Kunes Aidan Coffey Jiahui Guo Katarina Kralova |
| author_sort | Ondrej Jandourek |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T06:42:48Z |
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| id | doaj.art-4dbea44fdabe4fd38e3a262c46e5f149 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T06:42:48Z |
| publishDate | 2014-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-4dbea44fdabe4fd38e3a262c46e5f1492022-12-22T02:57:41ZengMDPI AGMolecules1420-30492014-01-0119165167110.3390/molecules19010651molecules19010651N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological PropertiesOndrej Jandourek0Martin Dolezal1Pavla Paterova2Vladimir Kubicek3Matus Pesko4Jiri Kunes5Aidan Coffey6Jiahui Guo7Katarina Kralova8Department of Medicinal Chemistry and Drug Analysis, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech RepublicDepartment of Medicinal Chemistry and Drug Analysis, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech RepublicDepartment of Biological and Medical Sciences, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech RepublicDepartment of Biophysics and Physical Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech RepublicDepartment of Environmental Ecology, Faculty of Natural Sciences, Comenius University, Mlynska Dolina CH-2, Bratislava 842 15, SlovakiaDepartment of Inorganic and Organic Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech RepublicDepartment of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork, IrelandDepartment of Biological Sciences, Cork Institute of Technology, Bishopstown, Cork, IrelandInstitute of Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska Dolina CH-2, Bratislava 842 15, SlovakiaIn 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.http://www.mdpi.com/1420-3049/19/1/651pyrazinamide derivatives in vitro biological evaluationmicrowave-assisted synthesistuberculosislipophilicity |
| spellingShingle | Ondrej Jandourek Martin Dolezal Pavla Paterova Vladimir Kubicek Matus Pesko Jiri Kunes Aidan Coffey Jiahui Guo Katarina Kralova N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological Properties Molecules pyrazinamide derivatives in vitro biological evaluation microwave-assisted synthesis tuberculosis lipophilicity |
| title | N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological Properties |
| title_full | N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological Properties |
| title_fullStr | N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological Properties |
| title_full_unstemmed | N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological Properties |
| title_short | N-Substituted 5-Amino-6-methylpyrazine-2,3-dicarbonitriles: Microwave-Assisted Synthesis and Biological Properties |
| title_sort | n substituted 5 amino 6 methylpyrazine 2 3 dicarbonitriles microwave assisted synthesis and biological properties |
| topic | pyrazinamide derivatives in vitro biological evaluation microwave-assisted synthesis tuberculosis lipophilicity |
| url | http://www.mdpi.com/1420-3049/19/1/651 |
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