Introduction of Nonacidic Side Chains on 6-Ethylcholane Scaffolds in the Identification of Potent Bile Acid Receptor Agonists with Improved Pharmacokinetic Properties

Finamore, Claudia; Baronissi, Giuliana; Marchianò, Silvia; Di Leva, Francesco; Carino, Adriana; Monti, Maria; Limongelli, Vittorio; Zampella, Angela; Fiorucci, Stefano; Sepe, Valentina

doi:10.3390/molecules24061043

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Journal article

Introduction of Nonacidic Side Chains on 6-Ethylcholane Scaffolds in the Identification of Potent Bile Acid Receptor Agonists with Improved Pharmacokinetic Properties

2019-3-16

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Molecules. - MDPI AG. - 2019, vol. 24, no. 6, p. 1043

Organic Chemistry

English As a cellular bile acid sensor, farnesoid X receptor (FXR) and the membrane G-coupled receptor (GPBAR1) participate in maintaining bile acid, lipid, and glucose homeostasis. To date, several selective and dual agonists have been developed as promising pharmacological approach to metabolic disorders, with most of them possessing an acidic conjugable function that might compromise their pharmacokinetic distribution. Here, guided by docking calculations, nonacidic 6-ethyl cholane derivatives have been prepared. In vitro pharmacological characterization resulted in the identification of bile acid receptor modulators with improved pharmacokinetic properties.

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English

Open access status

gold

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DOI 10.3390/molecules24061043
ISSN 1420-3049

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https://sonar.ch/global/documents/186160

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