title: Synthesis and antimycobacterial evaluation of N-substituted 5-chloropyrazine-2-carboxamides.
abstract: To develop new potential antimycobacterial drugs, a series of pyrazinamide derivatives was designed, synthesized and tested for their ability to inhibit the growth of selected mycobacterial strains (Mycobacterium tuberculosis H37Rv, Mycobacterium kansasii and two strains of Mycobacterium avium). This Letter is focused on binuclear pyrazinamide analogues containing the -CONH-CH2- bridge, namely on N-benzyl-5-chloropyrazine-2-carboxamides with various substituents on the phenyl ring and their comparison with some analogously substituted 5-chloro-N-phenylpyrazine-2-carboxamides. Compounds from the N-benzyl series exerted lower antimycobacterial activity against M. tuberculosis H37Rv then corresponding anilides, however comparable with pyrazinamide (12.5-25 μg/mL). Remarkably, 5-chloro-N-(4-methylbenzyl)pyrazine-2-carboxamide (8, MIC=3.13 μg/mL) and 5-chloro-N-(2-chlorobenzyl)pyrazine-2-carboxamide (1, MIC=6.25 μg/mL) were active against M. kansasii, which is naturally unsusceptible to PZA. Basic structure-activity relationships are presented.
authors: Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové 500 05, Czech Republic. barbora.servusova@faf.cuni.cz
authors: Barbora
authors: B
authors: Servusová
authors: Jana
authors: J
authors: Vobicková
authors: Pavla
authors: P
authors: Paterová
authors: Vladimír
authors: V
authors: Kubíček
authors: Jiří
authors: J
authors: Kuneš
authors: Martin
authors: M
authors: Doležal
authors: Jan
authors: J
authors: Zitko
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D011719:Pyrazines