Antiobesity designed multiple ligands: Synthesis of pyrazole fatty acid amides and evaluation as hypophagic agents

Searching for new antiobesity agents, a new series of fatty acid amide derivatives of 1,5-diarylpyrazole have been synthesized as dual peroxisome proliferator activated receptor alpha (PPARα)/cannabinoid receptor ligands. The compounds have been evaluated in vivo and in vitro as PPARα activators and as cannabinoids in two tests of the mouse tetrad. In vivo, food intake studies have been performed with all the compounds. No significant cannabinoid activity has been found but some compounds behaved as potent PPARα activators. Several compounds showed anorexigenic properties reducing food intake in rats.

Pyrazole fatty acid amides have been synthesized from suitable pyrazole esters, and oleyl and hexadecyl amines. The compounds reduce food intake in rats. The oleyl derivatives are PPARα activators.Figure optionsDownload as PowerPoint slide