Title :

Effect of 6-Benzoyl-benzothiazol-2-one scaffold on the pharmacological profile of α-alkoxyphenylpropionic acid derived PPAR agonists

Author(s) :

Hurtevent, Aurélie [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 [JPArc]
Le Naour, Morgan [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 [JPArc]
Leclerc, Veronique [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 [JPArc]
Carato, Pascal [Auteur]
CIC - Poitiers
Melnyk, Patricia [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 [JPArc]
Hennuyer, Nathalie [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires [RNMCD - U1011]
Staels, Bart [Auteur]
Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD]
Beucher-Gaudin, Monique [Auteur]
Institut de Recherches SERVIER [IRS]
Caignard, Daniel-Henri [Auteur]
Institut de Recherches SERVIER [IRS]
Dacquet, Catherine [Auteur]
Institut de Recherches SERVIER [IRS]
Lebegue, Nicolas [Auteur]
Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U1172 Inserm - U837 [JPArc]

Publisher :

Informa Healthcare

Publication date :

2020

English keyword(s) :

Type 2 diabetes
PPAR
SPPARM
benzothiazol-2-one
body weight gain

HAL domain(s) :

Chimie/Chimie thérapeutique
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Endocrinologie et métabolisme

English abstract : [en]

A series of nitrogen heterocycles containing α–ethoxyphenylpropionic acid derivatives were designed as dual PPARα/γ agonist ligands for the treatment of type 2 diabetes (T2D) and its complications. 6-Benzoyl-benzothiazol-2-one ...
Show more >A series of nitrogen heterocycles containing α–ethoxyphenylpropionic acid derivatives were designed as dual PPARα/γ agonist ligands for the treatment of type 2 diabetes (T2D) and its complications. 6-Benzoyl-benzothiazol-2-one was the most tolerant of the tested heterocycles in which incorporation of O-methyl oxime ether and trifluoroethoxy group followed by enantiomeric resolution led to the (S)-stereoisomer 44 b displaying the best in vitro pharmacological profile. Compound 44 b acted as a very potent full PPARγ agonist and a weak partial agonist on the PPARα receptor subtype. Compound 44 b showed high efficacy in an ob/ob mice model with significant decreases in serum triglyceride, glucose and insulin levels but mostly with limited body-weight gain and could be considered as a selective PPARγ modulator (SPPARγM).Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Non spécifiée

Popular science :

Non

Collections :

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

Source :

Harvested from HAL

Submission date :

2021-06-12T03:00:58Z