Inhibition of M. tuberculosis in vitro in monocytes and in mice by aminomethylene pyrazinamide analogs

Synthesis and antimycobacterial properties of N-substituted 6-amino-5-cyanopyrazine-2-carboxamides

“…The previously mentioned interesting and unique properties of pyrazinamide and/or its derivatives (sterilizing activity, multiple mechanisms of action) motivate further research in this field. Recently, promising results were published by Chung et al 7 (aminomethylene pyrazinamide analogues) and Ancizu et al 8 (quinoxaline-2-carboxamide 1,4-di-N-oxide derivatives). Other ongoing studies are concerned with the pharmacokinetics, bioavailability and dosage regimen of PZA as reported in the review by Mitchison et al 9 This study is focused on non-aromatically N-substituted 6-amino-5-cyanopyrazine-2-carboxamides.…”

Seeking potent anti-tubercular agents: design and synthesis of substituted-N-(6-(4-(pyrazine-2-carbonyl)piperazine/homopiperazine-1-yl)pyridin-3-yl)benzamide derivatives as anti-tubercular agents

“…1 Reports reveal that the analogues of pyrazine and pyrazinamide can exhibit higher anti-TB activity against MTB. [3][4][5][6][7][8][9][10][11][12][13][14][15][16] Substituted N-phenylpyrazine-2-carboxamides synthesized by Dolezal et al were evaluated in vitro for antimycobacterial activity. It was shown that compound N-(4-(triuoromethyl)phenyl)pyrazine-2-carboxamide (A), N-(2bromo-3-methylphenyl)pyrazine-2-carboxamide (B) and N-(3iodo-4-methylphenyl)pyrazine-2-carboxamide (C) exhibited four times higher activity (MIC # 2 mg L À1 ) than the standard drug PZA (¼8 mg L À1 ).…”

“…al., and Chandran et. al., reported several piperazine based active antitubercular agents of which 4-(2-(7-methoxy-2-oxo-1,5-naphthyridin-1-(2H)-yl)ethyl)-N-(4-nitrophenyl)piperazine-1-carboxamide 21 and N-(4-chlorophenyl)-4-(6-nitro-4-oxo-4H-benzo[e] [1,3]thiazin-2-yl)piperazine-1-carbothioamide 18 were the most active compounds with IC 50 0.29 mM and 0.51 mM in the DNA supercoiling assay and MTB MIC 3.45 mM and 4.41 mM respectively. 21,22 In our previous work, we linked a piperazine moiety to the pyridine nucleus of phenanthridine and these compounds were shown to exhibit good to excellent anti-TB activity with MICs ranging from 1.56 mg mL À1 to 50 mg mL À1 .…”

Pyrazinecarboxylic Acid Derivatives with Antimycobacterial Activity

“…Novel aminomethylene analogues of PZA (see Fig. 4, general structure IV) were tested (Chung et al, 2008). The activity of N -(pyrrolidin-1-ylmethyl)pyrazine-2-carboxamide was higher than that of PZA when administered with rifalazil or RIF in a mouse model of infection.…”