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Discovery of Potent Dual PPAR? Agonists/CB1 Ligands.

ABSTRACT: This letter describes the synthesis and in vitro and in vivo evaluation of dual ligands targeting the cannabinoid and peroxisome proliferator-activated receptors (PPAR). These compounds were obtained from fusing the pharmacophores of fibrates and the diarylpyrazole rimonabant, a cannabinoid receptor antagonist. They are the first examples of dual compounds with nanomolar affinity for both PPAR? and cannabinoid receptors. Besides, lead compound 2 proved to be CB1 selective. Unexpectedly, the phenol intermediates tested were equipotent (compound 1 as compared to 2) or even more potent (compound 3 as compared with 4). This discovery opens the way to design new dual ligands.

SUBMITTER: Perez-Fernandez R

PROVIDER: S-EPMC4056814 | biostudies-other | 2011 Nov

REPOSITORIES: biostudies-other

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Discovery of Potent Dual PPARα Agonists/CB1 Ligands.

Pérez-Fernández Ruth R Fresno Nieves N Macías-González Manuel M Elguero José J Decara Juan J Girón Rocío R Rodríguez-Álvarez Ana A Martín María Isabel MI Rodríguez de Fonseca Fernando F Goya Pilar P

ACS medicinal chemistry letters 20110916 11

This letter describes the synthesis and in vitro and in vivo evaluation of dual ligands targeting the cannabinoid and peroxisome proliferator-activated receptors (PPAR). These compounds were obtained from fusing the pharmacophores of fibrates and the diarylpyrazole rimonabant, a cannabinoid receptor antagonist. They are the first examples of dual compounds with nanomolar affinity for both PPARα and cannabinoid receptors. Besides, lead compound 2 proved to be CB1 selective. Unexpectedly, the phen ...[more]

PMID: 24936232

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