1.
Bioorg Med Chem Lett
; 20(3): 881-6, 2010 Feb 01.
Artículo
en Inglés
| MEDLINE
| ID: mdl-20064717
RESUMEN
Structure-guided drug design led to the identification of a class of spirocyclic ureas which potently inhibit human 11beta-HSD1 in vitro. Lead compound 10j was shown to be orally bioavailable in three species, distributed into adipose tissue in the mouse, and its (R) isomer 10j2 was efficacious in a primate pharmacodynamic model.
Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/antagonistas & inhibidores , Diseño de Fármacos , Urea/administración & dosificación , Urea/farmacocinética , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/metabolismo , Administración Oral , Animales , Sitios de Unión/fisiología , Disponibilidad Biológica , Células CHO , Cricetinae , Cricetulus , Humanos , Macaca fascicularis , Ratones , Ratas , Relación Estructura-Actividad , Urea/análogos & derivados
2.
Bioorg Med Chem Lett
; 19(13): 3541-5, 2009 Jul 01.
Artículo
en Inglés
| MEDLINE
| ID: mdl-19457666
RESUMEN
Structure-based drug design led to the identification of a novel class of potent, low MW alkylamine renin inhibitors. Oral administration of lead compound 21l, with MW of 508 and IC(50) of 0.47nM, caused a sustained reduction in mean arterial blood pressure in a double transgenic rat model of hypertension.