Substituted 5-aroylpyrazine-2-carboxylic acid derivatives: synthesis and biological activity.
Homolytic aroylation of pyrazine nucleus with various substituted aromatic carbaldehydes afforded a series of 5-aroylpyrazine-2-carboxylic acid derivatives. The synthetic approach, analytical and spectroscopic data of all compounds synthesized, their preliminary in vitro evaluation of antituberculotic and antifungal activities, cytotoxicity data and subsequent SAR studies are presented. Among all derivatives prepared, only 5-(4-chlorobenzoyl)-pyrazine-2-carbothioamide (3d) showed promising activity (90% inhibition) against Mycobacterium tuberculosis. The highest antifungal effect (MIC<1.95 microM ml(-1)) against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for 5-benzoylpyrazine-2-carbothioamide (3a). Thioamides exhibited higher in vitro antimicrobial activity than the corresponding amides.
Dolezal
M
M
Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 50005 Hradec Králové, Czech Republic. dolezalm@faf.cuni.cz
Jampílek
J
J
Osicka
Z
Z
Kunes
J
J
Buchta
V
V
Víchová
P
P
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D018938:Caco-2 Cells; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D002264:Carboxylic Acids; D011719:Pyrazines