1-(Piperidin-3-yl)thymine amides as inhibitors of M. tuberculosis thymidylate kinase

A series of readily accessible 1-(piperidin-3-yl)thymine amides was designed, synthesised and evaluated as Mycobacterium tuberculosis TMPK (MtbTMPK) inhibitors. In line with the modelling results, most inhibitors showed reasonable MtbTMPK inhibitory activity. Compounds 4b and 4i were slightly more p...

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Autores principales: Jian, Yanlin, Risseeuw, Martijn D. P., Froeyen, Mathy, Song, Lijun, Cappoen, Davie, Cos, Paul, Munier-Lehmann, Hélène, van Calenbergh, Serge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920704/
https://www.ncbi.nlm.nih.gov/pubmed/31822127
http://dx.doi.org/10.1080/14756366.2019.1662790
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author Jian, Yanlin
Risseeuw, Martijn D. P.
Froeyen, Mathy
Song, Lijun
Cappoen, Davie
Cos, Paul
Munier-Lehmann, Hélène
van Calenbergh, Serge
author_facet Jian, Yanlin
Risseeuw, Martijn D. P.
Froeyen, Mathy
Song, Lijun
Cappoen, Davie
Cos, Paul
Munier-Lehmann, Hélène
van Calenbergh, Serge
author_sort Jian, Yanlin
collection PubMed
description A series of readily accessible 1-(piperidin-3-yl)thymine amides was designed, synthesised and evaluated as Mycobacterium tuberculosis TMPK (MtbTMPK) inhibitors. In line with the modelling results, most inhibitors showed reasonable MtbTMPK inhibitory activity. Compounds 4b and 4i were slightly more potent than the parent compound 3. Moreover, contrary to the latter, amide analogue 4g was active against the avirulent M. tuberculosis H37Ra strain (MIC(50)=35 µM). This finding opens avenues for future modifications.
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spelling pubmed-69207042020-01-02 1-(Piperidin-3-yl)thymine amides as inhibitors of M. tuberculosis thymidylate kinase Jian, Yanlin Risseeuw, Martijn D. P. Froeyen, Mathy Song, Lijun Cappoen, Davie Cos, Paul Munier-Lehmann, Hélène van Calenbergh, Serge J Enzyme Inhib Med Chem Research Paper A series of readily accessible 1-(piperidin-3-yl)thymine amides was designed, synthesised and evaluated as Mycobacterium tuberculosis TMPK (MtbTMPK) inhibitors. In line with the modelling results, most inhibitors showed reasonable MtbTMPK inhibitory activity. Compounds 4b and 4i were slightly more potent than the parent compound 3. Moreover, contrary to the latter, amide analogue 4g was active against the avirulent M. tuberculosis H37Ra strain (MIC(50)=35 µM). This finding opens avenues for future modifications. Taylor & Francis 2019-12-11 /pmc/articles/PMC6920704/ /pubmed/31822127 http://dx.doi.org/10.1080/14756366.2019.1662790 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Paper
Jian, Yanlin
Risseeuw, Martijn D. P.
Froeyen, Mathy
Song, Lijun
Cappoen, Davie
Cos, Paul
Munier-Lehmann, Hélène
van Calenbergh, Serge
1-(Piperidin-3-yl)thymine amides as inhibitors of M. tuberculosis thymidylate kinase
title 1-(Piperidin-3-yl)thymine amides as inhibitors of M. tuberculosis thymidylate kinase
title_full 1-(Piperidin-3-yl)thymine amides as inhibitors of M. tuberculosis thymidylate kinase
title_fullStr 1-(Piperidin-3-yl)thymine amides as inhibitors of M. tuberculosis thymidylate kinase
title_full_unstemmed 1-(Piperidin-3-yl)thymine amides as inhibitors of M. tuberculosis thymidylate kinase
title_short 1-(Piperidin-3-yl)thymine amides as inhibitors of M. tuberculosis thymidylate kinase
title_sort 1-(piperidin-3-yl)thymine amides as inhibitors of m. tuberculosis thymidylate kinase
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920704/
https://www.ncbi.nlm.nih.gov/pubmed/31822127
http://dx.doi.org/10.1080/14756366.2019.1662790
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