Synthesis of 4-(3-biaryl)quinoline sulfones as potent liver X receptor agonists.

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Ullrich JW, Morris R, Bernotas RC, Travins JM, Jetter J, Unwalla R, Quinet E, Nambi P, Feingold I, Huselton C, Enroth C, Wilhelmsson A, Goos-Nilsson A, Wrobel J

Synthesis of 4-(3-biaryl)quinoline sulfones as potent liver X receptor agonists.

Bioorg Med Chem Lett. 2010 May 1;20(9):2903-7. doi: 10.1016/j.bmcl.2010.03.031. Epub 2010 Mar 9.

PubMed ID

20382019 [ View in PubMed

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Abstract

A series of 4-(3-biaryl)quinolines with sulfone substituents on the terminal aryl ring (8) was prepared as potential LXR agonists. High affinity LXRbeta ligands with generally modest binding selectivity over LXRalpha and excellent agonist potency in LXR functional assays were identified. Many compounds had LXRbeta binding IC(50) values <10 nM while the most potent had EC(50) values <1.0 nM in an ABCA1 mRNA induction assay in J774 mouse cells with efficacy comparable to T0901317. Sulfone 8a was further evaluated in LDL (-/-) mice and shown to reduce atherosclerotic lesion progression.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
TO-901317	Oxysterols receptor LXR-alpha	IC 50 (nM)	13	N/A	N/A	Details