Imagen de Portada
Código QR

Synthesis of benzopyran derivatives as PPARα and/or PPARγ activators

We describe the synthesis of 26 compounds, small polycerasoidol analogs, that are Lipinski’s rule-of-five compliant. In order to confirm key structural features to activate PPARα and/or PPARγ, we have adopted structural modifications in the following parts: (i) the benzopyran core (hydrophobic nucle...

Descripción completa

Autores principales: Bermejo, Almudena, Barrachina, Isabel, El Aouad, Noureddine, Franck, Xavier, Chahboune, Nadia, Andreu, Inmaculada, Figadère, Bruno, Vila, Laura, hennuyer, Nathalie, Staels, Bart, Dacquet, Catherine, Caignard, Daniel H., Sanz, María-Jesús, Cortés, Diego, Cabedo, Nuria
Formato: article
Lenguaje:Inglés
Publicado: Elsevier 2020
Materias:
Polycerasoidol
PPARα agonism
PPARγ agonism
F60 Plant physiology and biochemistry
Benzopyrene
Acceso en línea:http://hdl.handle.net/20.500.11939/6461
https://www.sciencedirect.com/science/article/pii/S0968089619316505
Sumario:We describe the synthesis of 26 compounds, small polycerasoidol analogs, that are Lipinski’s rule-of-five compliant. In order to confirm key structural features to activate PPARα and/or PPARγ, we have adopted structural modifications in the following parts: (i) the benzopyran core (hydrophobic nucleus) by benzopyran-4-one, dihydrobenzopyran or benzopyran-4-ol; (ii) the side chain at 2-position by shortening to C3, C4 and C5-carbons versus C-9-carbons of polycerasoidol; (iii) the carboxylic group (polar head) by oxygenated groups (hydroxyl, acetoxy, epoxide, ester, aldehyde) or non-oxygenated motifs (allyl and alkyl). Benzopyran-4-ones 6, 12, 13 and 17 as well as dihydrobenzopyrans 22, 24 and 25 were able to activate hPPARα, whereas benzopyran-4-one (7) with C5-carbons in the side chain exhibited hPPARγ agonism. According to our previous docking studies, SAR confirm that the hydrophobic nucleus (benzopyran-4-one or dihydrobenzopyran) is essential to activate PPARα and/or PPARγ, and the flexible linker (side alkyl chain) should containg at least C5-carbon atoms to activate PPARγ. By contrast, the polar head (“carboxylic group”) tolerated several oxygenated groups but also non-oxygenated motifs. Taking into account these key structural features, small polycerasoidol analogs might provide potential active molecules useful in the treatment of dyslipidemia and/or type 2 diabetes.

Ejemplares similares