Design, synthesis and anti-mycobacterial evaluation of some new N-phenylpyrazine-2-carboxamides

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F16%3A10328655" target="_blank" >RIV/00179906:_____/16:10328655 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11160/16:10328655

Výsledek na webu

<a href="http://www.degruyter.com/view/j/chempap.2016.70.issue-5/chempap-2015-0246/chempap-2015-0246.xml" target="_blank" >http://www.degruyter.com/view/j/chempap.2016.70.issue-5/chempap-2015-0246/chempap-2015-0246.xml</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1515/chempap-2015-0246" target="_blank" >10.1515/chempap-2015-0246</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Design, synthesis and anti-mycobacterial evaluation of some new N-phenylpyrazine-2-carboxamides

Popis výsledku v původním jazyce

N-Phenylpyrazine-2-carboxamides (anilides of pyrazinoic acids with simple substituents in various positions) were previously shown to possess significant biological activities in vitro, markedly anti-mycobacterial and photosynthesis-inhibiting activity. Based on structure-activity relationships (SAR) extracted from previously published series, 25 new anilides of non-substituted pyrazinoic acid (POA), 5-CH3-POA, 6-Cl-POA, 5-tert-butyl-POA and 5-tert-butyl-6-Cl-POA were designed and synthesised. The phenyl part was substituted with simple hydrophobic substituents chosen from methyl and halogens. 5-tert-Butyl-N-(5-fluoro-2-methylphenyl) pyrazine-2-carboxamide (9), N-(3-chloro-4-methylphenyl)-5-methylpyrazine-2-carboxamide (12), 6-chloro-N-(3-chloro-4-methylphenyl) pyrazine-2-carboxamide (13) and 6-chloro-N-(5-iodo-2-methylphenyl) pyrazine- 2-carboxamide (18) possessed whole cell anti-mycobacterial activity in vitro against Mycobacterium tuberculosis H37Rv with minimum inhibitory concentration (MIC) of around 10 mu M. Importantly, no cytotoxicity in the HepG2 model was detected in vitro at the concentrations tested and the estimated IC50 values were in hundreds of mu M, indicating promising selectivity. N-(3-Chloro-4-methylphenyl) pyrazine-2-carboxamide (11) and N-(4-chloro-2-iodophenyl) pyrazine-2-carboxamide (21) exerted significant activity against Mycobacterium kansasii with MIC 12.6 mu M and 8.7 mu M, respectively. No activity was detected against Mycobacterium avium. SAR were in accordance with those observed for the derivatives previously published.

Název v anglickém jazyce

Design, synthesis and anti-mycobacterial evaluation of some new N-phenylpyrazine-2-carboxamides

Popis výsledku anglicky

N-Phenylpyrazine-2-carboxamides (anilides of pyrazinoic acids with simple substituents in various positions) were previously shown to possess significant biological activities in vitro, markedly anti-mycobacterial and photosynthesis-inhibiting activity. Based on structure-activity relationships (SAR) extracted from previously published series, 25 new anilides of non-substituted pyrazinoic acid (POA), 5-CH3-POA, 6-Cl-POA, 5-tert-butyl-POA and 5-tert-butyl-6-Cl-POA were designed and synthesised. The phenyl part was substituted with simple hydrophobic substituents chosen from methyl and halogens. 5-tert-Butyl-N-(5-fluoro-2-methylphenyl) pyrazine-2-carboxamide (9), N-(3-chloro-4-methylphenyl)-5-methylpyrazine-2-carboxamide (12), 6-chloro-N-(3-chloro-4-methylphenyl) pyrazine-2-carboxamide (13) and 6-chloro-N-(5-iodo-2-methylphenyl) pyrazine- 2-carboxamide (18) possessed whole cell anti-mycobacterial activity in vitro against Mycobacterium tuberculosis H37Rv with minimum inhibitory concentration (MIC) of around 10 mu M. Importantly, no cytotoxicity in the HepG2 model was detected in vitro at the concentrations tested and the estimated IC50 values were in hundreds of mu M, indicating promising selectivity. N-(3-Chloro-4-methylphenyl) pyrazine-2-carboxamide (11) and N-(4-chloro-2-iodophenyl) pyrazine-2-carboxamide (21) exerted significant activity against Mycobacterium kansasii with MIC 12.6 mu M and 8.7 mu M, respectively. No activity was detected against Mycobacterium avium. SAR were in accordance with those observed for the derivatives previously published.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

—

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chemical Papers

ISSN

0366-6352

e-ISSN

—

Svazek periodika

70

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

SK - Slovenská republika

Počet stran výsledku

9

Strana od-do

649-657

Kód UT WoS článku

000376512000014

EID výsledku v databázi Scopus

2-s2.0-84959199726