Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros




Base de datos
Asunto de la revista
Intervalo de año de publicación
1.
Mol Divers ; 26(1): 73-96, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33385288

RESUMEN

N-furfuryl piperazine ureas disclosed by scientists at GSK Tres Cantos were chosen as antimycobacterial hits from a phenotypic whole-cell screen. Bioisosteric replacement of the furan ring in the GSK Tres Cantos molecules with a phenyl ring led to molecule (I) with an MIC of 1 µM against Mtb H37Rv, low cellular toxicity (HepG2 IC50 ~ 80 µM), good DMPK properties and specificity for Mtb. With the aim of delineating the SAR associated with (I), fifty-five analogs were synthesized and screened against Mtb. The SAR suggests that the piperazine ring, benzyl urea and piperonyl moieties are essential signatures of this series. Active compounds in this series are metabolically stable, have low cellular toxicity and are valuable leads for optimization. Molecular docking suggests these molecules occupy the Q0 site of QcrB like Q203. Bioisosteric replacement of N-furfuryl piperazine-1-carboxamides yielded molecule (I) a novel lead with satisfactory PD, metabolism, and toxicity profiles.


Asunto(s)
Mycobacterium tuberculosis , Antituberculosos/farmacología , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Estructura Molecular , Piperazinas/farmacología , Relación Estructura-Actividad , Urea/farmacología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA