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

Authors :
Giuliana Baronissi
Adriana Carino
Valentina Sepe
Francesco Saverio Di Leva
Silvia Marchianò
Vittorio Limongelli
Claudia Finamore
Maria Chiara Monti
Stefano Fiorucci
Angela Zampella
Finamore, Claudia
Baronissi, Giuliana
Marchianò, Silvia
Di Leva, Francesco Saverio
Carino, Adriana
Chiara Monti, Maria
Limongelli, Vittorio
Zampella, Angela
Fiorucci, Stefano
Sepe, Valentina
Source :
Molecules, Volume 24, Issue 6, Molecules, Vol 24, Iss 6, p 1043 (2019)
Publication Year :
2019
Publisher :
Multidisciplinary Digital Publishing Institute, 2019.

Abstract

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.

Details

Language :
English
ISSN :
14203049
Database :
OpenAIRE
Journal :
Molecules
Accession number :
edsair.doi.dedup.....c24c0b58de091b4b0daa58dc1e34a1ce
Full Text :
https://doi.org/10.3390/molecules24061043