Title :

Synthesis of benzopyran derivatives as PPARα and/ or PPARγ activators

Author(s) :

Bermejo, Almudena [Auteur]
Universitat de València [UV]
Barrachina, Isabel [Auteur]
Universitat de València [UV]
El Aouad, Noureddine [Auteur]
Universitat de València [UV]
Franck, Xavier [Auteur]
Chimie Organique et Bioorganique : Réactivité et Analyse [COBRA]
Chahboune, Nadia [Auteur]
Universitat de València [UV]
Andreu, Inmaculada [Auteur]
Universitat de València [UV]
Figadère, Bruno [Auteur]
Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique [Châtenay-Malabry] [LabEx LERMIT]
Vila, Laura [Auteur]
Universitat de València [UV]
Hennuyer, Nathalie [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Staels, Bart [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Dacquet, Catherine [Auteur]
Institut de Recherches Internationales Servier [Suresnes] [IRIS]
Caignard, Daniel [Auteur]
Institut de Recherches Internationales Servier [Suresnes] [IRIS]
Sanz, María-Jesús [Auteur]
Universitat de València [UV]
Cortes, Diego [Auteur]
Universitat de València [UV]
Cabedo, Nuria [Auteur]
Universitat de València [UV]

Journal title :

Bioorganic and Medicinal Chemistry Letters

Pages :

115162

Publisher :

Elsevier

Publication date :

2019-10

ISSN :

0960-894X

HAL domain(s) :

Chimie

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (EGID) - U1011

Source :

Harvested from HAL