1-(1-Arylethylpiperidin-4-yl)thymine Analogs as Antimycobacterial TMPK Inhibitors.
Molecules
; 25(12)2020 Jun 17.
Article
em En
| MEDLINE
| ID: mdl-32560578
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).
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Timina
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Proteínas de Bactérias
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Núcleosídeo-Fosfato Quinase
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Inibidores Enzimáticos
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Mycobacterium tuberculosis
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Antituberculosos
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article