Abstract : 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).
https://hal.univ-lille.fr/hal-02464519
Contributeur : Lilloa Université de Lille
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Soumis le : lundi 3 février 2020 - 11:47:30
Dernière modification le : vendredi 21 février 2020 - 01:01:19
Aurélie Hurtevent, Morgan Le Naour, Veronique Leclerc, Pascal Carato, Patricia Melnyk, et al.. Effect of 6-Benzoyl-benzothiazol-2-one scaffold on the pharmacological profile of α-alkoxyphenylpropionic acid derived PPAR agonists. Journal of Enzyme Inhibition and Medicinal Chemistry, Informa Healthcare, 2020, Journal of Enzyme Inhibition and Medicinal Chemistry, 35 (1), pp.524-538. ⟨10.1080/14756366.2020.1713771⟩. ⟨hal-02464519⟩
