title: N-substituted 5-amino-6-methylpyrazine-2,3-dicarbonitriles: microwave-assisted synthesis and biological properties.
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.
authors.affiliation: Department of Medicinal Chemistry and Drug Analysis, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. jando6aa@faf.cuni.cz.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Jandourek
authors.affiliation: Department of Medicinal Chemistry and Drug Analysis, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. dolezalm@faf.cuni.cz.
authors.forename: Martin
authors.initials: M
authors.lastname: Dolezal
authors.affiliation: Department of Medicinal Chemistry and Drug Analysis, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. pavla.paterova@fnhk.cz.
authors.forename: Pavla
authors.initials: P
authors.lastname: Paterova
authors.affiliation: Department of Medicinal Chemistry and Drug Analysis, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. kubicek@faf.cuni.cz.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kubicek
authors.affiliation: Department of Medicinal Chemistry and Drug Analysis, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. matus.pesko@gmail.com.
authors.forename: Matus
authors.initials: M
authors.lastname: Pesko
authors.affiliation: Department of Medicinal Chemistry and Drug Analysis, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. kunes@faf.cuni.cz.
authors.forename: Jiri
authors.initials: J
authors.lastname: Kunes
authors.affiliation: Department of Medicinal Chemistry and Drug Analysis, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. aidan.coffey@cit.ie.
authors.forename: Aidan
authors.initials: A
authors.lastname: Coffey
authors.affiliation: Department of Medicinal Chemistry and Drug Analysis, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. gjh0517@yahoo.com.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Medicinal Chemistry and Drug Analysis, Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic. kata.kralova@gmail.com.
authors.forename: Katarina
authors.initials: K
authors.lastname: Kralova
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002736:Chloroplasts / Q000187:drug effects / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D054879:Halogenation; D006540:Herbicides / Q000138:chemical synthesis / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D008872:Microwaves; D020102:Mycobacterium smegmatis / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009570:Nitriles / Q000138:chemical synthesis / Q000494:pharmacology*; D010788:Photosynthesis / Q000187:drug effects; D011719:Pyrazines / Q000138:chemical synthesis / Q000494:pharmacology*; D018724:Spinacia oleracea / Q000187:drug effects / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D006540:Herbicides; D009570:Nitriles; D011719:Pyrazines