ABSTRACT
A series of esters of the 3-aminopyrazine-2-carboxylic acid as potential antimycobacterial drugs was synthesized. A CEM Discover microwave reactor with an autosampler Explorer 24 which served to accelerate the reaction was used for synthesis. The prepared products were characterized by IR, 1H NMR, 13C NMR spectra, elementary analysis and melting points. Log P and ClogP values were calculated. Final products were evaluated in vitro for their antimycobacterial activity. The most active compound was hexyl 3-aminopyrazine-2-carboxylate (7), whose antimycobacterial activity (MIC) against M. tuberculosis H37Rv was 6.25 µg/mL.
Subject(s)
Antitubercular Agents/pharmacology , Mycobacterium tuberculosis/drug effects , Pyrazines/pharmacology , Antitubercular Agents/chemical synthesis , Esters , Microbial Sensitivity Tests , Mycobacterium tuberculosis/growth & development , Pyrazines/chemical synthesisABSTRACT
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.
