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

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Kher S, Lake K, Sircar I, Pannala M, Bakir F, Zapf J, Xu K, Zhang SH, Liu J, Morera L, Sakurai N, Jack R, Cheng JF

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

Bioorg Med Chem Lett. 2007 Aug 15;17(16):4442-6. Epub 2007 Jun 10.

PubMed ID

17587573 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
TO-901317	Oxysterols receptor LXR-alpha	EC 50 (nM)	40	7.5	22	Details