This paper describes preparation and biological evaluation of pyrazinamide analogues. Pyrazinamide with its simple structure gives a good opportunity for further modification regarding an increase of its antimycobacterial activity. We prepared a series of compounds derived from pyrazine-2,5-dicarbonitrile with arylamino substitution in position 3. All compounds were assayed in vitro against major Mycobacterium and various Fungi species. The best activity was found in 3-{[3-(trifluoromethyl)phenyl]amino}pyrazine-2,5-dicarbonitrile 11 with the value of 6.25 micromol(-1) against M. tuberculosis H(37)Rv and moderate activity against minor Mycobacterium pathogens.
- MeSH
- Absidia účinky léků MeSH
- antifungální látky farmakologie chemická syntéza MeSH
- antituberkulotika farmakologie chemická syntéza MeSH
- Aspergillus fumigatus účinky léků MeSH
- Candida účinky léků MeSH
- financování organizované MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium účinky léků MeSH
- nitrily farmakologie chemická syntéza MeSH
- pyrazinamid analogy a deriváty farmakologie chemická syntéza MeSH
- pyraziny farmakologie chemická syntéza MeSH
- Trichosporon účinky léků MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- vztahy mezi strukturou a aktivitou MeSH
Unsubstituted, halogenated and/or alkylated pyrazine-2-carboxylic acid amides connected via -CONH- bridge with substituted anilines were synthesized using currently known synthetic pathways. The synthetic approach, analytical, spectroscopic, lipophilicity and biological data of 20 newly synthesized compounds are presented. Structure-activity relationships among the chemical structures, the antimycobacterial, antifungal, photosynthesis inhibiting and antialgal activity of the evaluated substituted N-phenylpyrazine-2-carboxamides are discussed. 5-tert-Butyl-6-chloro-N-(3-trifluoromethylphenyl)pyrazine-2-carboxamide (19) has shown the highest activity against Mycobacterium tuberculosis H(37)Rv (MIC=3.13 microg/mL). The highest antifungal effect against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for N-(3-trifluoromethylphenyl)pyrazine-2-carboxamide (14, MIC=62.5 micromol/mL). The highest reduction of chlorophyll content in Chlorella vulgaris was found for pyrazine-2-carboxylic acid (3-trifluoromethylphenyl)amide (9, IC(50)=12.1 micromol/L).
- MeSH
- amidy farmakologie chemická syntéza chemie MeSH
- antibakteriální látky farmakologie chemická syntéza chemie MeSH
- antifungální látky farmakologie chemická syntéza chemie MeSH
- Cercopithecus aethiops MeSH
- Chlorella vulgaris metabolismus účinky léků MeSH
- chlorofyl metabolismus MeSH
- chloroplasty metabolismus účinky léků MeSH
- financování organizované MeSH
- herbicidy farmakologie chemická syntéza chemie MeSH
- mikrobiální testy citlivosti MeSH
- Mycobacterium tuberculosis účinky léků MeSH
- pyraziny farmakologie chemická syntéza chemie MeSH
- Spinacia oleracea metabolismus účinky léků MeSH
- Vero buňky MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
Condensation of the corresponding chlorides of some substituted pyrazine-2-carboxylic acids (pyrazine-2-carboxylic acid, 6-chloropyrazine-2-carboxylic acid, 5-tert-butylpyrazine-2-carboxylic acid or 5-tert-butyl-6-chloropyrazine-2-carboxylic acid) with various ring-substituted aminothiazoles or anilines yielded a series of amides. The syntheses, analytical and spectroscopic data of thirty newly prepared compounds are presented. Structure-activity relationships between the chemical structures and the anti-mycobacterial, antifungal and photosynthesis-inhibiting activity of the evaluated compounds are discussed. 3,5-Bromo-4-hydroxyphenyl derivatives of substituted pyrazinecarboxylic acid, 16-18, have shown the highest activity against Mycobacterium tuberculosis H(37)Rv (54-72% inhibition). The highest antifungal effect against Trichophyton mentagrophytes, the most susceptible fungal strain tested, was found for 5-tert-butyl-6-chloro-N-(4-methyl-1,3-thiazol-2-yl)pyrazine-2-carboxamide (8, MIC =31.25 micromol x mL(-1)). The most active inhibitors of oxygen evolution rate in spinach Molecules 2006, 11,243 chloroplasts were the compounds 5-tert-butyl-6-chloro-N-(5-bromo-2-hydroxyphenyl)- pyrazine-2-carboxamide (27, IC(50) = 41.9 micromol x L(-1)) and 5-tert-butyl-6-chloro-N-(1,3- thiazol-2-yl)-pyrazine-2-carboxamide (4, IC50 = 49.5 micromol x L(-1)).
- MeSH
- amidy chemická syntéza farmakologie MeSH
- antibakteriální látky farmakologie chemická syntéza MeSH
- antifungální látky farmakologie chemická syntéza MeSH
- financování organizované MeSH
- fotosyntéza účinky léků MeSH
- kyseliny karboxylové chemie MeSH
- Mycobacterium tuberculosis účinky léků MeSH
- pyraziny chemie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- MeSH
- pyrazinamid analogy a deriváty farmakologie chemie MeSH
- techniky in vitro MeSH
- tuberkulóza farmakoterapie MeSH
- Publikační typ
- kongresy MeSH
