Design and Synthesis of Highly Active Peroxisome Proliferator‐Activated Receptor (PPAR) β/δ Inverse Agonists with Prolonged Cellular Activity | Zendy

Toth Philipp M. | Zendy; Lieber Sonja | Zendy; Scheer Frithjof M. | Zendy; Schumann Tim | Zendy; Schober Yvonne | Zendy; Nockher Wolfgang A. | Zendy; Adhikary Till | Zendy; MüllerBrüsselbach Sabine | Zendy; Müller Rolf | Zendy; Diederich Wibke E. | Zendy

Premium

Design and Synthesis of Highly Active Peroxisome Proliferator‐Activated Receptor (PPAR) β/δ Inverse Agonists with Prolonged Cellular Activity

Author(s) -

Toth Philipp M.,

Lieber Sonja,

Scheer Frithjof M.,

Schumann Tim,

Schober Yvonne,

Nockher Wolfgang A.,

Adhikary Till,

MüllerBrüsselbach Sabine,

Müller Rolf,

Diederich Wibke E.

Publication year - 2016

Publication title -

chemmedchem

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.817

H-Index - 100

eISSN - 1860-7187

pISSN - 1860-7179

DOI - 10.1002/cmdc.201500594

Subject(s) - peroxisome , inverse agonist , peroxisome proliferator activated receptor , chemistry , agonist , receptor , biological activity , carboxylate , stereochemistry , biochemistry , pharmacology , biology , in vitro

Based on 3‐(((4‐(hexylamino)‐2‐methoxyphenyl)amino)sulfonyl)‐2‐thiophenecarboxylic acid methyl ester (ST247, compound 2 ), a recently described peroxisome proliferator‐activated receptor (PPAR)β/δ‐selective inverse agonist, we designed and synthesized a series of structurally related ligands. The structural modifications presented herein ultimately resulted in a series of ligands that display increased cellular activity relative to 2 . Moreover, with methyl 3‐( N ‐(2‐(2‐ethoxyethoxy)‐4‐(hexylamino)phenyl)sulfamoyl)thiophene‐2‐carboxylate (PT‐S264, compound 9 u ), biologically relevant plasma concentrations in mice were achieved. The compounds presented in this study will provide useful novel tools for future investigations addressing the role of PPARβ/δ in physiological and pathophysiological processes.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here

Accelerating Research