Pharmaceuticals for treating obesity

A - Human Necessities – 61 – K

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A61K 31/40 (2006.01)

Patent

CA 2386750

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 characterized 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 fat- fed C57BL/6J mice. This compound and other PPAR-gamma antagonists/partial agonists and pharmaceutically acceptable salts are effective in the treatment of obesity and/or diabetes and/or insulin resistance.

L'invention concerne des composés qui sont antagonistes des agonistes PPAR-gamma forts, tels que la rosiglitazone, et qui sont également des agonistes partiels du récepteur PPAR-gamma. Ces composés sont des agents actifs permettant de corriger ou de réduire l'obésité. Par exemple, le 1-(p-chlorobenzyle)-5-chloro-3-thiophenylindole-2-acide carboxylique, est considéré comme étant un ligand puissant et sélectif pour le PPAR-gamma lequel présente un agoniste partiel (effets maximum <30 % par rapport à la rosiglitazone) et une activité antagoniste dans des dosages acellulaires et des dosages à base de cellules pour le récepteur PPAR-gamma. Le composé est un agent puissant permettant de réduire l'obésité et l'insulinorésistance chez des souris C57BL/6J engraissées. Ce composé et d'autres antagonistes/agonistes partiels PPAR-gamma ainsi que des sels pharmaceutiquement acceptables sont efficaces dans le traitement de l'obésité et/ou des diabètes et/ou de l'insulinorésistance.

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