1.
Bioorg Med Chem Lett
; 16(24): 6328-33, 2006 Dec 15.
Article
in English
| MEDLINE
| ID: mdl-17005394
ABSTRACT
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.
Subject(s)
Cinnamates/chemical synthesis , Cinnamates/pharmacokinetics , Peroxisome Proliferator-Activated Receptors/physiology , Humans , Hypoglycemic Agents/therapeutic use , Ligands , PPAR alpha/physiology , PPAR gamma/physiology , Structure-Activity Relationship , Thiazolidinediones/chemical synthesis , Thiazolidinediones/therapeutic use
2.
Bioorg Med Chem Lett
; 15(1): 51-5, 2005 Jan 03.
Article
in English
| MEDLINE
| ID: mdl-15582409
ABSTRACT
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.