Prof P Steel
No more applications being accepted
Funded PhD Project (UK Students Only)
About the Project
Fragment Based Drug Discovery (FBDD), is a popular medicinal chemistry strategy in which new drug structures are built up through the combination smaller weakly binding units (fragments). Whilst FBDD has been successfully applied to a number of studies this has been achieved using a relatively limited set of heteroaromatic scaffolds. Preliminary studies have shown that whilst theoretical chemotherapeutic space is diverse in terms of structure and physico-chemical properties, most heterocyclic structures are located in small islands of structural similarity with medicinal chemists being unable to explore unoccupied and therefore unprecedented regions. In this collaborative project we propose build on this analysis and establish a set of new previously undescribed heterocyclic systems as a new tool box for FBDD with a specific application for the generation of novel inhibitors of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme in the de novo biosynthetic pathway of pyrimidines, with considerable current interest as new anti-parasitic (Leishmania and T.Cruzi) and antiviral (Dengue, SARS- CoV2) chemotherapies. A particular challenge for FBDD is functionalising heterocyclic fragments to enable desired connections to be established, with alternative substituents requiring de novo and often challenging synthesis. Consequently, a specific goal of the studentship will be to develop generic complementary methods for late stage functionalisation of each heterocycle that can be applied in a sequential and vectorially diverse manner. This will build on specific expertise within the consortium and explore approaches based on C-H borylation, direct metalation and fluorination.
Eligibility: The position is only open to applicants from the UK for fees purposes. Early applications are strongly encouraged as the position will be filled when a suitable candidate is identified.
For informal enquiries please contact Prof Patrick Steel ([Email Address Removed]).