2. Academic Validation
  3. Alkylamino derivatives of pyrazinamide: synthesis and antimycobacterial evaluation

Alkylamino derivatives of pyrazinamide: synthesis and antimycobacterial evaluation

  • Bioorg Med Chem Lett. 2014 Jan 15;24(2):450-3. doi: 10.1016/j.bmcl.2013.12.054.
Barbora Servusová 1,  Pavla Paterová 2,  Jana Mandíková 2,  Vladimír Kubíček 2,  Radim Kučera 2,  Jiří Kuneš 2,  Martin Doležal 2,  Jan Zitko 3
Affiliations

Affiliations

  • 1 Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové 500 05, Czech Republic. Electronic address: barbora.servusova@faf.cuni.cz.
  • 2 Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové 500 05, Czech Republic.
  • 3 Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové 500 05, Czech Republic. Electronic address: jan.zitko@faf.cuni.cz.
PMID: 24388809 DOI: 10.1016/j.bmcl.2013.12.054
Abstract

A series of pyrazinamide derivatives with alkylamino substitution was designed, synthesized and tested for their ability to inhibit the growth of selected mycobacterial, Bacterial and Fungal strains. The target structures were prepared from the corresponding 5-chloro (1) or 6-chloropyrazine-2-carboxamide (2) by nucleophilic substitution of chlorine by various non-aromatic amines (alkylamines). To determine the influence of alkyl substitution, corresponding amino derivatives (1a, 2a) and compounds with phenylalkylamino substitution were prepared. Some of the compounds exerted antimycobacterial activity against Mycobacterium tuberculosis H37Rv significantly better than standard pyrazinamide and corresponding starting compounds (1 and 2). Basic structure-activity relationships are presented. Only weak Antibacterial and no Antifungal activity was detected.

Keywords

5-Chloropyrazine-2-carboxamide; 6-Chloropyrazine-2-carboxamide; Alkylamines; Antimycobacterial activity; Cytotoxicity.

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