SAR studies: designing potent and selective LXR agonists

  • Bioorg Med Chem Lett. 2006 Jun 1;16(11):3055-60. doi: 10.1016/j.bmcl.2006.02.050.
Jason W Szewczyk  1 ,  Shaei Huang ,  Jayne Chin ,  Jenny Tian ,  Lyndon Mitnaul ,  Raymond L Rosa ,  Larry Peterson ,  Carl P Sparrow ,  Alan D Adams
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. [email protected]
PMID: 16529931 DOI: 10.1016/j.bmcl.2006.02.050
Abstract

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.