title: Synthesis and antimycobacterial properties of N-substituted 6-amino-5-cyanopyrazine-2-carboxamides.
abstract: A series of fifteen new compounds related to pyrazinamide (PZA) were synthesized, characterized with analytical data and screened for antimycobacterial, antifungal and antibacterial activity. The series consists of 6-chloro-5-cyanopyrazine-2-carboxamide and N-substituted 6-amino-5-cyanopyrazine-2-carboxamides, derived from the previous by nucleophilic substitution with various non-aromatic amines (alkylamines, cycloalkylamines, heterocyclic amines). Some of the compounds exerted antimycobacterial activity against Mycobacterium tuberculosis equal to pyrazinamide (12.5-25 μg/mL). More importantly, 6-chloro-5-cyanopyrazine-2-carboxamide and 5-cyano-6-(heptylamino)pyrazine-2-carboxamide were active against Mycobacterium kansasii and Mycobacterium avium, which are unsusceptible to PZA. Basic structure-activity relationships are presented. Only weak antifungal and no antibacterial activity was detected.
authors.affiliation: Faculty of Pharmacy, Charles University, Heyrovskeho 1203, Hradec Kralove 500 05, Czech Republic. jan.zitko@faf.cuni.cz
authors.forename: Jan
authors.initials: J
authors.lastname: Zitko
authors.forename: Martin
authors.initials: M
authors.lastname: Dolezal
authors.forename: Michaela
authors.initials: M
authors.lastname: Svobodova
authors.forename: Marcela
authors.initials: M
authors.lastname: Vejsova
authors.forename: Jiri
authors.initials: J
authors.lastname: Kunes
authors.forename: Radim
authors.initials: R
authors.lastname: Kucera
authors.forename: Petr
authors.initials: P
authors.lastname: Jilek
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000588:Amines / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D050296:Microbial Viability / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011719:Pyrazines / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000588:Amines; D000900:Anti-Bacterial Agents; D011719:Pyrazines; C066548:cyanopyrazine