1.
Bioorg Med Chem Lett
; 17(10): 2869-73, 2007 May 15.
Artículo
en Inglés
| MEDLINE
| ID: mdl-17400452
RESUMEN
Modulation of cAMP levels has been linked to insulin secretion in preclinical animal models and in humans. The high expression of PDE-10A in pancreatic islets suggested that inhibition of this enzyme may provide the necessary modulation to elicit increased insulin secretion. Using an HTS approach, we have identified quinoline-based PDE-10A inhibitors as insulin secretagogues in vitro. Optimized compounds were evaluated in vivo where improvements in glucose tolerance and increases in insulin secretion were measured.
Asunto(s)
Insulina/metabolismo , Islotes Pancreáticos/efectos de los fármacos , Inhibidores de Fosfodiesterasa/farmacología , Hidrolasas Diéster Fosfóricas/metabolismo , Quinolinas/farmacología , Diseño de Fármacos , Humanos , Secreción de Insulina , Islotes Pancreáticos/metabolismo , Estructura Molecular , Inhibidores de Fosfodiesterasa/síntesis química , Hidrolasas Diéster Fosfóricas/efectos de los fármacos , Quinolinas/síntesis química , Quinolinas/química , Relación Estructura-Actividad
2.
Bioorg Med Chem Lett
; 16(2): 297-301, 2006 Jan 15.
Artículo
en Inglés
| MEDLINE
| ID: mdl-16275080
RESUMEN
A series of oxazole-substituted indanylacetic acids were prepared which show a spectrum of activity as ligands for PPAR nuclear receptor subtypes.