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1-(1-Arylethylpiperidin-4-yl)thymine Analogs as Antimycobacterial TMPK Inhibitors

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Abstract
<jats:p>A series of Mycobacterium tuberculosis TMPK (MtbTMPK) inhibitors based on a reported compound 3 were synthesized and evaluated for their capacity to inhibit MtbTMPK catalytic activity and the growth of a virulent M. tuberculosis strain (H37Rv). Modifications of the scaffold of 3 failed to afford substantial improvements in MtbTMPK inhibitory activity and antimycobacterial activity. Optimization of the substitution pattern of the D ring of 3 resulted in compound 21j with improved MtbTMPK inhibitory potency (three-fold) and H37Rv growth inhibitory activity (two-fold). Moving the 3-chloro substituent of 21j to the para-position afforded isomer 21h, which, despite a 10-fold increase in IC50-value, displayed promising whole cell activity (minimum inhibitory concentration (MIC) = 12.5 μM).</jats:p>
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Organic Chemistry

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MLA
Jian, Yanlin, et al. “1-(1-Arylethylpiperidin-4-Yl)Thymine Analogs as Antimycobacterial TMPK Inhibitors.” Molecules, 2020, doi:10.3390/molecules25122805.
APA
Jian, Y., Hulpia, F., Risseeuw, M., Forbes, H. E., Caljon, G., Munier-Lehmann, H., … Van Calenbergh, S. (2020). 1-(1-Arylethylpiperidin-4-yl)thymine Analogs as Antimycobacterial TMPK Inhibitors. Molecules. https://doi.org/10.3390/molecules25122805
Chicago author-date
Jian, Yanlin, Fabian Hulpia, Martijn Risseeuw, He Eun Forbes, Guy Caljon, Hélène Munier-Lehmann, Helena I. M. Boshoff, and Serge Van Calenbergh. 2020. “1-(1-Arylethylpiperidin-4-Yl)Thymine Analogs as Antimycobacterial TMPK Inhibitors.” Molecules. https://doi.org/10.3390/molecules25122805.
Chicago author-date (all authors)
Jian, Yanlin, Fabian Hulpia, Martijn Risseeuw, He Eun Forbes, Guy Caljon, Hélène Munier-Lehmann, Helena I. M. Boshoff, and Serge Van Calenbergh. 2020. “1-(1-Arylethylpiperidin-4-Yl)Thymine Analogs as Antimycobacterial TMPK Inhibitors.” Molecules. doi:10.3390/molecules25122805.
Vancouver
1.
Jian Y, Hulpia F, Risseeuw M, Forbes HE, Caljon G, Munier-Lehmann H, et al. 1-(1-Arylethylpiperidin-4-yl)thymine Analogs as Antimycobacterial TMPK Inhibitors. Molecules. 2020;
IEEE
[1]
Y. Jian et al., “1-(1-Arylethylpiperidin-4-yl)thymine Analogs as Antimycobacterial TMPK Inhibitors,” Molecules, 2020.
@article{8667352,
  abstract     = {<jats:p>A series of Mycobacterium tuberculosis TMPK (MtbTMPK) inhibitors based on a reported compound 3 were synthesized and evaluated for their capacity to inhibit MtbTMPK catalytic activity and the growth of a virulent M. tuberculosis strain (H37Rv). Modifications of the scaffold of 3 failed to afford substantial improvements in MtbTMPK inhibitory activity and antimycobacterial activity. Optimization of the substitution pattern of the D ring of 3 resulted in compound 21j with improved MtbTMPK inhibitory potency (three-fold) and H37Rv growth inhibitory activity (two-fold). Moving the 3-chloro substituent of 21j to the para-position afforded isomer 21h, which, despite a 10-fold increase in IC50-value, displayed promising whole cell activity (minimum inhibitory concentration (MIC) = 12.5 μM).</jats:p>},
  articleno    = {2805},
  author       = {Jian, Yanlin and Hulpia, Fabian and Risseeuw, Martijn and Forbes, He Eun and Caljon, Guy and Munier-Lehmann, Hélène and I. M. Boshoff, Helena and Van Calenbergh, Serge},
  issn         = {1420-3049},
  journal      = {Molecules},
  keywords     = {Organic Chemistry},
  language     = {eng},
  title        = {1-(1-Arylethylpiperidin-4-yl)thymine Analogs as Antimycobacterial TMPK Inhibitors},
  url          = {http://dx.doi.org/10.3390/molecules25122805},
  year         = {2020},
}

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