JOURNAL OF THE CZECH PHARMACEUTICAL SOCIETY AND THE SLOVAK PHARMACEUTICAL SOCIETY

Čes. slov. farm. 2013, 62(2):84-88

Aminopyrazinoic acid esters as potential antimycobacterial drugs

Martin Doležal1,*, Jana Vobicková1, Barbora Servusová1, Pavla Paterová2
1 Charles University in Prague, Faculty of Pharmacy, Department of Pharmaceutical Chemistry and Drug Control, Hradec Králové, Czech Republic
2 Department of Clinical Microbiology, University Hospital, Hradec Králové, Czech Republic

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.

Keywords: prodrugs; pyrazinoic acid esters; lipophilicity calculation; in vitro antimycobacterial activity
Grants and funding:

This work was financially supported by GAUK B-CH/710312, and IGA NT 13346. The publication is a result of the project implementation: Support of establishment, development, and mobility of quality research teams at the Charles University, Project Number CZ.1.07/2.3.00/30.20.0235, supported by The Education for Competitiveness Operational Programme (ECOP) and co-financed by the European Social Fund and the state budget of the Czech Republic. Authors wish to thank Ida Dufková for performing in vitro antifungal and antibacterial screening, and Assoc. Prof. Jiří Kuneš for recording of NMR spectra.

Received: February 14, 2013; Accepted: March 5, 2013; Published: February 1, 2013  Show citation

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Doležal M, Vobicková J, Servusová B, Paterová P. Aminopyrazinoic acid esters as potential antimycobacterial drugs. Čes. slov. farm. 2013;62(2):84-88.
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