Substituted N-Phenylpyrazine-2-carboxamides: synthesis and antimycobacterial evaluation.
The condensation of chlorides of substituted pyrazinecarboxylic acids with ringsubstituted anilines yielded twelve substituted pyrazinecarboxylic acid amides. The synthetic approach, analytical, and lipophilicity data of the newly synthesized compounds are presented. Two antituberculosis assays were used. Firstly, the antimycobacterial activity against four different Mycobacterium strains in a series of pyrazine derivatives was investigated. Secondly, the antimycobacterial evaluation was performed at the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) program. Interesting in vitro antimycobacterial activity was found, N-(3-iodo-4-methylphenyl) pyrazine-2-carboxamide (9) was most active derivative compound against M. tuberculosis (MIC < 2.0 micromol/L), while another iodo derivative 5-tert-butyl-6-chloro-N-(3-iodo-4-methyl-phenyl)pyrazine-2-carboxamide (12) was the most active compound in the TAACF antituberculosis screening program (IC(90) = 0.819 microg/mL).
Dolezal
Martin
M
Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, Hradec Králové, 500 05, Czech Republic. martin.dolezal@faf.cuni.cz
Zitko
Jan
J
Kesetovicová
Diana
D
Kunes
Jirí
J
Svobodová
Michaela
M
D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009162:Mycobacterium avium / Q000187:drug effects*; D019909:Mycobacterium kansasii / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011718:Pyrazinamide / Q000737:chemistry; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
C546531:5-tert-butyl-6-chloro-N-(3-iodo-4-methyl-phenyl)pyrazine-2-carboxamide; D000995:Antitubercular Agents; C546530:N-(3-iodo-4-methylphenyl)pyrazine-2-carboxamide; D011719:Pyrazines; D011718:Pyrazinamide