title: Synthesis and biological activity of 5-alkyl-6-(alkylsulfanyl)- or 5-alkyl-6-(arylsulfanyl)pyrazine-2-carboxamides and corresponding thioamides.
abstract: Nucleophilic substitution of chlorine in 5-alkyl-6-chloropyrazine-2-carboxamides with various alkyl and arylthiolates afforded 20 5-alkyl-6-(alkylsulfanyl)- and 5-alkyl-6-(arylsulfanyl)pyrazine-2-carboxamides. The reaction of the amides with Lawesson's reagent yielded the corresponding thioamides. The assessment of in vitro antimycobacterial and antifungal activity of the compounds was carried out. In both series, the antimycobacterial activity increases with increasing molecular weight of the alkylsulfanyl group in position 6 of the pyrazine ring. Thioamides exhibited higher activity than the corresponding amides. 5-Butyl-6-(phenylsulfanyl)pyrazine-2-carbothioamide (2j) possessed the highest activity (91% inhibition) against Mycobacterium tuberculosis and also the highest lipophilicity (log P = 4.95). Only a poor in vitro antifungal effect was noted in 5-butyl-6-(butylsulfanyl)pyrazine-2-carboxamide (1i) and 6-(ethylsulfanyl)-5-isobutylpyrazine-2-carbothioamide (2q) against Trichophyton mentagrophytes and Absidia corymbifera.
authors.affiliation: Department of Pharmaceutical Chemistry and Drug Control, Charles University in Prague, Faculty of Pharmacy, Hradec Králové, Czech Republic. krinkova@faf.cuni.cz
authors.forename: Jana
authors.initials: J
authors.lastname: Krinková
authors.forename: Martin
authors.initials: M
authors.lastname: Dolezal
authors.forename: Jirí
authors.initials: J
authors.lastname: Hartl
authors.forename: Vladimír
authors.initials: V
authors.lastname: Buchta
authors.forename: Milan
authors.initials: M
authors.lastname: Pour
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011719:Pyrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013854:Thioamides / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D000935:Antifungal Agents; D011719:Pyrazines; D013854:Thioamides