RESUMEN
A new series of coumarin inhibitors of DNA gyrase B bearing a N-propargyloxycarbamate at C-3' of various 5',5'-dialkylnoviose, including RU79115, were synthesised and their antibacterial activities have been delineated. Introduction of dialkyl substituents at 5'5'-position of noviose leads to coumarin analogues with improved in vitro and in vivo antibacterial activity.
Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Antiinfecciosos/química , Antiinfecciosos/farmacología , Cumarinas/química , Cumarinas/farmacología , Hexosas/farmacología , Hexosas/química , Pruebas de Sensibilidad MicrobianaRESUMEN
The design, synthesis, and in vitro biological activity of a series of 2-carboxy quinolone antagonists selective for the endothelin A receptor are presented. Introduction of a second acid group in position 3 of the quinolone ring increases dramatically the selectivity for ET(A).
Asunto(s)
Antagonistas de los Receptores de Endotelina , Quinolonas/química , Quinolonas/farmacología , Animales , Bioensayo , Ciclización , Diseño de Fármacos , Femenino , Humanos , Masculino , Ratones , Estructura Molecular , Ratas , Ratas Sprague-Dawley , Receptor de Endotelina A , Receptores de Endotelina/metabolismo , Relación Estructura-ActividadRESUMEN
The synthesis and biological profile in vitro of a series of coumarin inhibitors of gyrase B bearing a N-propargyloxycarbamate at C-3' of noviose is presented. Replacement of the 5-methylpyrrole-2-carboxylate of coumarin drugs with an N-propargyloxycarbamate bioisostere leads to analogues with improved antibacterial activity. Analysis of crystal structures of coumarin antibiotics with the 24 kDa N-terminal domain of the gyrase B protein provides a rational for the excellent inhibitory potency of C-3' N-alkoxycarbamates.
