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

• Main Authors: Aurélie Hurtevent (Author), Morgan Le Naour (Author), Veronique Leclerc (Author), Pascal Carato (Author), Patricia Melnyk (Author), Nathalie Hennuyer (Author), Bart Staels (Author), Monique Beucher-Gaudin (Author), Daniel-Henri Caignard (Author), Catherine Dacquet (Author), Nicolas Lebegue (Author)
• Format: Book
• Published: Taylor & Francis Group, 2020-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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).

Item Description

1475-6366
1475-6374
10.1080/14756366.2020.1713771