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1-(1-Arylethylpiperidin-4-yl)thymine analogs as antimycobacterial TMPK inhibitors

(2020) MOLECULES. 25(12).
Author
Organization
Abstract
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).
Keywords
Organic Chemistry, tuberculosis, Mycobacterium tuberculosis, MtbTMPK, 1-(1-arylethylpiperidin-4-yl)thymine, TUBERCULOSIS THYMIDYLATE KINASE, BACTERIAL RNA-POLYMERASE, MYCOBACTERIUM-TUBERCULOSIS, POTENT INHIBITORS, DISCOVERY, THYMIDINE, RESISTANCE, CHIMERA

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Citation

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MLA
Jian, Yanlin, et al. “1-(1-Arylethylpiperidin-4-Yl)Thymine Analogs as Antimycobacterial TMPK Inhibitors.” MOLECULES, vol. 25, no. 12, 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, 25(12). 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 25 (12). 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 25 (12). 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;25(12).
IEEE
[1]
Y. Jian et al., “1-(1-Arylethylpiperidin-4-yl)thymine analogs as antimycobacterial TMPK inhibitors,” MOLECULES, vol. 25, no. 12, 2020.
@article{8667352,
  abstract     = {{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).}},
  articleno    = {{2805}},
  author       = {{Jian, Yanlin and Hulpia, Fabian and Risseeuw, Martijn and Forbes, He Eun and Caljon, Guy and Munier-Lehmann, Hélène and Boshoff, Helena I. M. and Van Calenbergh, Serge}},
  issn         = {{1420-3049}},
  journal      = {{MOLECULES}},
  keywords     = {{Organic Chemistry,tuberculosis,Mycobacterium tuberculosis,MtbTMPK,1-(1-arylethylpiperidin-4-yl)thymine,TUBERCULOSIS THYMIDYLATE KINASE,BACTERIAL RNA-POLYMERASE,MYCOBACTERIUM-TUBERCULOSIS,POTENT INHIBITORS,DISCOVERY,THYMIDINE,RESISTANCE,CHIMERA}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{21}},
  title        = {{1-(1-Arylethylpiperidin-4-yl)thymine analogs as antimycobacterial TMPK inhibitors}},
  url          = {{http://dx.doi.org/10.3390/molecules25122805}},
  volume       = {{25}},
  year         = {{2020}},
}

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