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

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• 作者：Sunil Kher ; 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
• 关键词：Liver X receptor ; LXR agonist ; Indole ; ABCA1 ; SREBP-1c
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2007
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：15 August 2007
• 卷：17
• 期：16
• 页码：4442-4446
• 文件大小：275 K

摘要

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 LXRβ agonist with an EC₅₀ of 12 nM in the cofactor recruitment assay.