The University of Southampton
University of Southampton Institutional Repository

The synthesis of bioactive fluorinated bile acid analogues

The synthesis of bioactive fluorinated bile acid analogues
The synthesis of bioactive fluorinated bile acid analogues
Bile acids are naturally occurring steroidal compounds found within the bile of humans and other mammals. They have key physiological functions including the absorption of dietary lipids and hydrophobic drug molecules and they also are responsible for the regulation of cholesterol levels.

Bile acids have recently emerged also as signalling molecules and are agonists at the FXR nuclear receptor and TGR5 membrane-bound receptor, both of which are found in a multitude of human tissue types. Because of this, natural and semi-synthetic bile acids have steadily been gaining traction over recent decades as drug candidates. Pharmaceutical companies are investigating selective bile acid receptor agonists for a broad range of diseases including cancer, Parkinson’s disease, diabetes, metabolic disorder and liver disease, with some progressing well through clinical trials.

Fluorine is widely used during drug discovery to selectively modify a myriad of physiochemical properties including acidity, lipophilicity and hydrogen bond donating capacity. Therefore, the introduction of fluorine to potential bile acid drug candidates is of great interest. This thesis describes the synthesis of a number of fluorinated bile acid analogues, with a particular focus on targeting non-alcoholic steatohepatitis (NASH), a prominent condition underlying liver disease. A brief summary of preliminary biological data is also presented.
University of Southampton
Evans, David
30179541-a36b-4fd5-8988-38d59a7a97cd
Evans, David
30179541-a36b-4fd5-8988-38d59a7a97cd
Linclau, Bruno
19b9cacd-b8e8-4c65-af36-6352cade84ba

Evans, David (2020) The synthesis of bioactive fluorinated bile acid analogues. University of Southampton, Doctoral Thesis, 281pp.

Record type: Thesis (Doctoral)

Abstract

Bile acids are naturally occurring steroidal compounds found within the bile of humans and other mammals. They have key physiological functions including the absorption of dietary lipids and hydrophobic drug molecules and they also are responsible for the regulation of cholesterol levels.

Bile acids have recently emerged also as signalling molecules and are agonists at the FXR nuclear receptor and TGR5 membrane-bound receptor, both of which are found in a multitude of human tissue types. Because of this, natural and semi-synthetic bile acids have steadily been gaining traction over recent decades as drug candidates. Pharmaceutical companies are investigating selective bile acid receptor agonists for a broad range of diseases including cancer, Parkinson’s disease, diabetes, metabolic disorder and liver disease, with some progressing well through clinical trials.

Fluorine is widely used during drug discovery to selectively modify a myriad of physiochemical properties including acidity, lipophilicity and hydrogen bond donating capacity. Therefore, the introduction of fluorine to potential bile acid drug candidates is of great interest. This thesis describes the synthesis of a number of fluorinated bile acid analogues, with a particular focus on targeting non-alcoholic steatohepatitis (NASH), a prominent condition underlying liver disease. A brief summary of preliminary biological data is also presented.

Text
The Synthesis of Bioactive Fluorinated Bile Acid Analogues - Version of Record
Available under License University of Southampton Thesis Licence.
Download (14MB)

More information

Published date: January 2020

Identifiers

Local EPrints ID: 441967
URI: http://eprints.soton.ac.uk/id/eprint/441967
PURE UUID: 0981628a-bd48-448b-8405-af20567733a1
ORCID for Bruno Linclau: ORCID iD orcid.org/0000-0001-8762-0170

Catalogue record

Date deposited: 03 Jul 2020 16:30
Last modified: 17 Mar 2024 05:22

Export record

Contributors

Author: David Evans
Thesis advisor: Bruno Linclau ORCID iD

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×