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

Result code in 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>

Alternative codes found

RIV/00216208:11160/16:10328655

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FR - Pharmacology and apothecary chemistry

OECD FORD branch

—

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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

Publication year

2016

Confidentiality

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

Name of the periodical

Chemical Papers

ISSN

0366-6352

e-ISSN

—

Volume of the periodical

70

Issue of the periodical within the volume

5

Country of publishing house

SK - SLOVAKIA

Number of pages

9

Pages from-to

649-657

UT code for WoS article

000376512000014

EID of the result in the Scopus database

2-s2.0-84959199726