1.
Bioorg Med Chem Lett
; 17(4): 1056-61, 2007 Feb 15.
Article
in English
| MEDLINE
| ID: mdl-17157013
ABSTRACT
Modulation of PPAR activities represents an attractive approach for the treatment of diabetes with associated cardiovascular complications. The indanylacetic acid structural motif has proven useful in the generation of potent and tunable PPAR ligands. Modification of the substituents on the linker and the heterocycle tail group allowed for the modulation of the selectivity at the different receptor subtypes. Compound 33 was evaluated in vivo, where it displayed the desired reduction of glucose levels and increase in HDL levels in various animal models.
Subject(s)
Acetates/chemical synthesis , Acetates/pharmacology , Hypoglycemic Agents/chemical synthesis , Hypoglycemic Agents/pharmacology , Indans/chemical synthesis , Indans/pharmacology , PPAR alpha/agonists , PPAR delta/agonists , PPAR gamma/agonists , Animals , Area Under Curve , Blood Glucose/metabolism , Cells, Cultured , Cholesterol/blood , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/genetics , Dose-Response Relationship, Drug , Humans , Hydrolysis , Hypoglycemic Agents/pharmacokinetics , Indicators and Reagents , Lipoproteins, HDL/blood , Mice , Rats , Rats, Zucker , Rosiglitazone , Structure-Activity Relationship , Thiazolidinediones/therapeutic use
2.
Bioorg Med Chem Lett
; 14(12): 3155-9, 2004 Jun 21.
Article
in English
| MEDLINE
| ID: mdl-15149665
ABSTRACT
A series of (5-(2H)-isoxazolonyl) ureas were developed as nanomolar inhibitors of hormone-sensitive lipase, an enzyme of potential importance in the treatment of diabetes.
