Synthesis of fluorinated bioactive compounds

Lead Research Organisation: University of Southampton
Department Name: School of Chemistry

Abstract

Fluorination of organic molecules causes modification of a wide range of properties. In our group we study the influence of fluorination on hydrogen bonding properties of adjacent functional groups, on lipophilicity and on conformation. Hydrogen bonding (H-bonding) is one of the main transient intermolecular interactions involved in biological recognition events, and lipophilicity is regarded as one of the most important physical properties relevant to drug efficacy (next to potency).
We are currently particularly interested in hydroxylated substrates. In this project, we propose to investigate a series of fluorinated analogues of a number of lead molecules that are of interest in research towards treating Parkinson's disease. We will introduce unique fluorination patterns that are predicted to reduce their lipophilicity, without having to introduce polar groups that would potentially interfere in binding. In addition, the proposed modifications will introduce the potential for hydrogen bond interactions, which is expected to be beneficial for affinity.
Hence, the student will embark on the synthesis, isolation and characterisation of these analogues, and will be trained to understand the multitude of effects that result from fluorination. The analogues thus synthesised will be tested by an industrial collaborator.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509747/1 01/10/2016 30/09/2021
1940689 Studentship EP/N509747/1 28/09/2017 30/09/2021 Simon Holland
 
Title FLUORINATED BILE ACID DERIVATIVES 
Description Compounds of general formula (I): wherein R2a, R2b, R3a, R3b, R5, Y and R7 are as defined herein are selective agonists at the FXR receptor and are useful for the treatment or prevention of diseases and conditions including nonalcoholic steatohepatitis (NASH); primary biliary cirrhosis; primary sclerosing cholangitis; biliary atresia; cholestatic liver disease; hepatitis C infection; alcoholic liver disease; fibrosis; or liver damage arising from fibrosis. 
IP Reference WO2020025942 
Protection Patent application published
Year Protection Granted 2020
Licensed Commercial In Confidence
Impact in progress
 
Description Dextra Update Meetings 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Industry/Business
Results and Impact Update meetings and presentations with industrial collaborators and colleague on the same research project several times a year. The presentations detailed the work that had been carried out, the future work and included discussions of targets to synthesise as well as potential routes.
Year(s) Of Engagement Activity 2017,2018,2019,2020