Extending SAR of bile acids as FXR ligands: discovery of 23-N-(carbocinnamyloxy)-3alpha,7alpha-dihydroxy-6alpha-ethyl-24-nor-5beta-cholan- 23-amine.

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Gioiello A, Macchiarulo A, Carotti A, Filipponi P, Costantino G, Rizzo G, Adorini L, Pellicciari R

Extending SAR of bile acids as FXR ligands: discovery of 23-N-(carbocinnamyloxy)-3alpha,7alpha-dihydroxy-6alpha-ethyl-24-nor-5beta-cholan- 23-amine.

Bioorg Med Chem. 2011 Apr 15;19(8):2650-8. doi: 10.1016/j.bmc.2011.03.004. Epub 2011 Mar 10.

PubMed ID
21459580 [ View in PubMed
]
Abstract

Within our efforts in the discovery of novel potent and selective ligands for the FXR receptor, 23-N-(carbocinnamyloxy)-3alpha,7alpha-dihydroxy-6alpha-ethyl-24-nor-5beta-cholan- 23-amine was synthesized and evaluated for its ability to activate and modulate the biological response of the receptor. Alphascreen and RT-PCR revealed that the 6alpha-ethyl-24-norcholanyl-23-amine derivate behaves as full FXR agonist endowed with high binding affinity and efficacy, representing a promising lead candidate for further optimization. In addition, docking studies provide new insights into the molecular basis governing the partial and full agonist activity at FXR.

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Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
Chenodeoxycholic acidBile acid receptorEC 50 (nM)21000N/AN/ADetails