SAR studies: Designing potent and selective LXR agonists

Counterscreening compounds from a Merck PPAR program discovered lead 1, as a nanomolar LXR/PPAR dual agonist. SAR optimization developed a series of heterocyclic LXR agonists having excellent selectivity over all PPAR isoforms and possessing high LXR affinity and strong in vivo potency.

Graphical abstractLead screening at Merck identified a potent, dual LXR/PPAR agonist. SAR optimization developed a series of LXR specific heterocyclic agonists having excellent LXR affinity, good in vivo, potency and high selectivity versus other nuclear hormone receptors.Figure optionsDownload full-size imageDownload as PowerPoint slide