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

Abstract

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 (PPARa)/cannabinoid receptor ligands. The compounds have been evaluated in vivo and in vitro as PPARa activators and as can- nabinoids 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 PPARa activators. Several compounds showed anorexigenic properties reducing food intake in rats.This work has been supported by Grants from Proyectos de Excelencia de la Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía, Instituto de Salud Carlos III (FIS PI04/ 0834, CP04/0039, FIS 07/1226, Redes Temáticas RD06/001), Fun- dación Eugenio Rodríguez Pascual and Fundació Marató TV3. MCyT, proyectos: MAT2006-01997, SAF2006-13391-C03-02 and ‘‘Factoría de Cristalización” Consolider Ingenio 2010. M. Alva- rado is also grateful to the Xunta de Galicia (Spain) for a post- doctoral fellowship.Peer reviewe