Synthesis and Biological Evaluation of N-Alkyl-3-(alkylamino)-pyrazine-2-carboxamides

Molecules

Lucia Semelkova⁴  Klara Konecna⁴  Pavla Paterova⁴  Vladimir Kubicek⁴  Jiri Kunes⁴  Lucie Novakova⁴  Jan Marek⁴  Lieve Naesens¹  Matus Pesko³  Katarina Kralova²  Martin Dolezal⁴  Jan Zitko⁴ 

[1] Laboratory of Virology and Chemotherapy, Rega Institute KU Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium; E-Mail:;Institute of Chemistry, Faculty of Natural Sciences, Comenius University, Mlynska Dolina CH-2, Bratislava 84215, Slovakia; E-Mail:;Department of Environmental Ecology, Faculty of Natural Sciences, Comenius University, Mlynska Dolina CH-2, Bratislava 84215, Slovakia; E-Mail:;Faculty of Pharmacy, Charles University in Prague, Heyrovskeho 1203, Hradec Kralove 50005, Czech Republic; E-Mails:

关键词: pyrazinamide;    pyrazine;    alkylation;    aminodehalogenation;    antimycobacterial activity;    inhibition of photosynthetic electron transport;    structure-activity relationships;   

DOI  :  10.3390/molecules20058687

来源: mdpi

【 摘 要 】

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-methyl-pyrazine-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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.