Inside Cover: Design and Biological Evaluation of Novel, Balanced Dual PPARα/γ Agonists (ChemMedChem 6/2009)

✍ Scribed by Uwe Grether; Agnes Bénardeau; Jörg Benz; Alfred Binggeli; Denise Blum; Hans Hilpert; Bernd Kuhn; Hans Peter Märki; Markus Meyer; Peter Mohr; Kurt Püntener; Susanne Raab; Armin Ruf; Daniel Schlatter

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 439 KB
• Volume: 4
• Category: Article
• ISSN: 1860-7179
• DOI: 10.1002/cmdc.200990027

✦ Synopsis

Abstract

The inside cover picture shows the X‐ray‐determined binding of an α‐ethoxy‐phenyl‐propionic acid‐derived dual PPARα/γ agonist in complex with PPARα (yellow) and PPARγ (blue). The high α‐selectivity of this phenylthiazole (IC~50~ γ/α = 37; EC~50~ γ/α = 7) can be rationalized mainly by a single residue difference, Cys 275 (α) vs. Gly 284 (γ), leading to three additional interactions with the terminal p‐Cl‐Ph group. In addition, its binding site is highlighted in a surface representation of the PPARα protein. For more details, see the Communication by U. Grether et al. on p. 951 ff.magnified image