Conformationally constrained farnesoid X receptor (FXR) agonists: heteroaryl replacements of the naphthalene.

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Bass JY, Caravella JA, Chen L, Creech KL, Deaton DN, Madauss KP, Marr HB, McFadyen RB, Miller AB, Mills WY, Navas F 3rd, Parks DJ, Smalley TL Jr, Spearing PK, Todd D, Williams SP, Wisely GB

Conformationally constrained farnesoid X receptor (FXR) agonists: heteroaryl replacements of the naphthalene.

Bioorg Med Chem Lett. 2011 Feb 15;21(4):1206-13. doi: 10.1016/j.bmcl.2010.12.089. Epub 2010 Dec 23.

PubMed ID
21256005 [ View in PubMed
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Abstract

To improve on the drug properties of GSK8062 1b, a series of heteroaryl bicyclic naphthalene replacements were prepared. The quinoline 1c was an equipotent FXR agonist with improved drug developability parameters relative to 1b. In addition, analog 1c lowered body weight gain and serum glucose in a DIO mouse model of diabetes.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AtorvastatinCytochrome P450 3A4IC 50 (nM)5100N/AN/ADetails
MidazolamCytochrome P450 3A4IC 50 (nM)>33000N/AN/ADetails
NifedipineCytochrome P450 3A4IC 50 (nM)11000N/AN/ADetails