Discovery and SAR of cinnolines/quinolines as liver X receptor (LXR) agonists with binding selectivity for LXRbeta.

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Hu B, Unwalla R, Collini M, Quinet E, Feingold I, Goos-Nilsson A, Wihelmsson A, Nambi P, Wrobel J

Discovery and SAR of cinnolines/quinolines as liver X receptor (LXR) agonists with binding selectivity for LXRbeta.

Bioorg Med Chem. 2009 May 15;17(10):3519-27. doi: 10.1016/j.bmc.2009.04.012. Epub 2009 Apr 12.

PubMed ID
19394832 [ View in PubMed
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Abstract

A series of cinnolines/quinolines was prepared and it was found that 4-phenyl-cinnoline/quinolines with either a 2',3' or 2',5'-disubstituted benzyloxy moiety or the 1-Me-7-indole methoxy moiety on the meta position of the 4-phenyl ring showed good binding selectivity for LXRbeta over LXRalpha. The LXRbeta binding selective modulators displayed good activity for inducing ABCA1 gene expression in J774 macrophage cell line and poor efficacy in the LXRalpha Gal4 functional assay. 26, 37 and 41 were examined for their ability to induce SREBP-1c gene expression in Huh-7 liver cell line and they were weak partial agonists.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
TO-901317Oxysterols receptor LXR-alphaEC 50 (nM)135N/AN/ADetails
TO-901317Oxysterols receptor LXR-alphaIC 50 (nM)14000N/AN/ADetails