2-Aryl-N-acyl indole derivatives as liver X receptor (LXR) agonists

  • Bioorg Med Chem Lett. 2007 Aug 15;17(16):4442-6. doi: 10.1016/j.bmcl.2007.06.017.
Sunil Kher  1 ,  Kirk Lake ,  Ila Sircar ,  Madhavi Pannala ,  Farid Bakir ,  James Zapf ,  Kui Xu ,  Shao-Hui Zhang ,  Juping Liu ,  Lisa Morera ,  Naoki Sakurai ,  Rick Jack ,  Jie-Fei Cheng
Affiliations
  • 1. Department of Chemistry, Tanabe Research Laboratories USA, Inc., 4540 Towne Centre Court, San Diego, CA 92121, USA.
PMID: 17587573 DOI: 10.1016/j.bmcl.2007.06.017
Abstract

Structure-activity relationship studies on a series of Boc-indole derivatives as LXR agonists are described. Compound 1 was identified as an LXR agonist through structure-based virtual screening followed by high-throughput gene profiling. Replacement of the indan linker portion in 1 with an open-chain linker resulted in compounds with similar or improved in vitro potency and cellular functional activity. The Boc group at the N-1 position of the indole moiety can be replaced with a benzoyl group. The SAR studies led to the identification of compound 8, a potent LXRbeta agonist with an EC50 of 12 nM in the cofactor recruitment assay.