1.
Bioorg Med Chem Lett
; 14(4): 1039-42, 2004 Feb 23.
Artículo
en Inglés
| MEDLINE
| ID: mdl-15013019
RESUMEN
The SAR from our peptide libraries was exploited to design a series of potent deoxybenzoin PTP-1B inhibitors. The introduction of an ortho bromo substituent next to the difluoromethylphosphonate warhead gave up to 20-fold increase in potency compared to the desbromo analogues. In addition, these compounds were orally bioavailable and active in the animal models of non-insulin dependent diabetes mellitus (NIDDM).
Asunto(s)
Benzoína/farmacología , Inhibidores Enzimáticos/farmacología , Proteínas Tirosina Fosfatasas/antagonistas & inhibidores , Administración Oral , Animales , Benzoína/análogos & derivados , Benzoína/síntesis química , Disponibilidad Biológica , Línea Celular , Supervivencia Celular/efectos de los fármacos , Diabetes Mellitus/enzimología , Diabetes Mellitus/metabolismo , Diseño de Fármacos , Inhibidores Enzimáticos/síntesis química , Insectos , Ratones , Ratones Noqueados , Modelos Animales , Proteína Tirosina Fosfatasa no Receptora Tipo 1 , Relación Estructura-Actividad
2.
Bioorg Med Chem Lett
; 14(4): 1043-8, 2004 Feb 23.
Artículo
en Inglés
| MEDLINE
| ID: mdl-15013020
RESUMEN
A series of benzotriazole phenyldifluoromethylphosphonic acids were found to be potent PTP-1B inhibitors. Molecular modeling on the X-ray crystal structure of the lead structure led to the design of potent PTP-1B inhibitors that show moderate selectivity against TC-PTP, a very closely related protein tyrosine phosphatase.