Canna~Fangled Abstracts

Discovery of Potent Dual PPARα Agonists/CB1 Ligands.

By September 16, 2011 No Comments
2011 Sep 16;2(11):793-7. doi: 10.1021/ml200091q. eCollection 2011.

pm1Discovery of Potent Dual PPARα 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 cannabinoidreceptor 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 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.

KEYWORDS:

Dual ligands; PPARα; cannabinoids; fibrates; neuroprotective; rimonabant

PMID:

 24936232
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