| abstract |
Compounds which are antagonists of strong PPAR-gamma agonists, such as rosiglitazone, and are also partial agonists of the PPAR-gamma receptor, are active agents for correcting or reducing obesity. For example, 1-(p- chlorobenzyl)-5-chloro-3-thiophenylindole-2-carboxylic acid, is characterize d as being a potent and selective ligand for PPAR-gamma which has partial agonist (<30 % maximal effects relative to rosiglitazone) and antagonist activity in cell-free and cell-based assays for the PPAR-gamma receptor. The compound is a potent agent for reducing obesity and insulin resistance in fa t- fed C57BL/6J mice. This compound and other PPAR-gamma antagonists/partial agonists and pharmaceutically acceptable salts are effective in the treatmen t of obesity and/or diabetes and/or insulin resistance. |