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

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Affiliation

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.

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