1.
J Med Chem
; 47(16): 3934-7, 2004 Jul 29.
Artículo
en Inglés
| MEDLINE
| ID: mdl-15267232
RESUMEN
Glycogen synthase kinase-3 (GSK3) is involved in signaling from the insulin receptor. Inhibitors of GSK3 are expected to effect lowering of plasma glucose similar to insulin, making GSK3 an attractive target for the treatment of type 2 diabetes. Herein we report the discovery of a series of potent and selective GSK3 inhibitors. Compounds 7-12 show oral activity in an in vivo model of type II diabetes, and 9 and 12 have desirable PK properties.
Asunto(s)
Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Imidazoles/síntesis química , Piridinas/síntesis química , Pirroles/síntesis química , Administración Oral , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Glucógeno Sintasa Quinasa 3 beta , Humanos , Imidazoles/farmacocinética , Imidazoles/farmacología , Piridinas/farmacocinética , Piridinas/farmacología , Pirroles/farmacocinética , Pirroles/farmacología , Ratas , Ratas Zucker
2.
Bioorg Med Chem Lett
; 17(17): 4832-6, 2007 Sep 01.
Artículo
en Inglés
| MEDLINE
| ID: mdl-17624775
RESUMEN
SAR about the B-ring of a series of N(2)-aroyl anthranilamide factor Xa (fXa) inhibitors is described. B-ring o-aminoalkylether and B-ring p-amine probes of the S1' and S4 sites, respectively, afforded picomolar fXa inhibitors that performed well in in vitro anticoagulation assays.