Статья

7-Hydroxy-benzopyran-4-one Derivatives: A Novel Pharmacophore of Peroxisome Proliferator-Activated Receptor α and -γ (PPARα and γ) Dual Agonists

Azadeh MatinFaculty of Pharmacy, The University of Sydney, NSW 2006, Sydney, AustraliaNavnath S. GavandeFaculty of Pharmacy, The University of Sydney, NSW 2006, Sydney, AustraliaMoon S. KimFaculty of Pharmacy, The University of Sydney, NSW 2006, Sydney, AustraliaNancy X. YangFaculty of Pharmacy, The University of Sydney, NSW 2006, Sydney, AustraliaNoeris K. SalamFaculty of Pharmacy, The University of Sydney, NSW 2006, Sydney, AustraliaJane R. HanrahanFaculty of Pharmacy, The University of Sydney, NSW 2006, Sydney, AustraliaRebecca H. RoubinFaculty of Pharmacy, The University of Sydney, NSW 2006, Sydney, AustraliaDavid E. HibbsFaculty of Pharmacy, The University of Sydney, NSW 2006, Sydney, Australia

2009en

ABI

Аннотация

Design, synthesis, and in vitro bioevaluation of a new class of potential dual PPARalpha and gamma agonists discovered through a structure-driven design paradigm are described. The 7-hydroxy-benzopyran-4-one moiety (includes flavones, flavanones, and isoflavones) is the key pharmacophore of these novel molecules, exhibiting similarity to the core structure of both fibrates and thiazolidinediones. New lead PPAR ligands were identified from "natraceuticals" and synthetic analogues. In total, 77 molecules, including chalcones, flavones, flavanones, isoflavones, and pyrazole derivatives, were screened and structure-activity relationship studies of the dual agonists undertaken. Compounds 68, 70, 72, and 76 were identified as novel and potent dual PPARalpha and gamma agonists. These novel molecules may have the potential to be the future leads in PPAR-related disorders, including type II diabetes mellitus and metabolic syndrome.

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Идентификаторы

DOI: 10.1021/jm900964r

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