1.
Bioorg Med Chem Lett
; 16(24): 6328-33, 2006 Dec 15.
Artículo
en Inglés
| MEDLINE
| ID: mdl-17005394
RESUMEN
PPAR ligands with varied subtype selectivity have been synthesized using an achiral aminomethyl dihydrocinnamate template. Several compounds in this series have demonstrated potent plasma glucose and triglyceride lowering capability in rodent models of type 2 diabetes.
Asunto(s)
Cinamatos/síntesis química , Cinamatos/farmacocinética , Receptores Activados del Proliferador del Peroxisoma/fisiología , Humanos , Hipoglucemiantes/uso terapéutico , Ligandos , PPAR alfa/fisiología , PPAR gamma/fisiología , Relación Estructura-Actividad , Tiazolidinedionas/síntesis química , Tiazolidinedionas/uso terapéutico
2.
Bioorg Med Chem Lett
; 15(1): 51-5, 2005 Jan 03.
Artículo
en Inglés
| MEDLINE
| ID: mdl-15582409
RESUMEN
Herein we describe a series of potent and selective PPARgamma agonists with moderate PPARalpha affinity and little to no affinity for other nuclear receptors. In vivo studies in a NIDDM animal model (ZDF rat) showed that these compounds are efficacious at low doses in glucose normalization and plasma triglyceride reduction. Compound 1b (LY519818) was selected from our SAR studies to be advanced to clinical evaluation for the treatment of type II diabetes.