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Researchers at the University of Oxford’s Department of Chemistry have developed methods for the rapid synthesis of compounds used in medicinal chemistry and drug discovery. These compounds feature in the core of several drug candidates currently in phase II and phase III clinical trials for various types of cancer.

A variety of tablets and injections

The technology, developed by Dr Stephen Fletcher and his team, is a method allowing rapid synthesis of organic molecules from simple and readily available starting materials. Their technology is the first to allow boronic acids to be used in asymmetric cross-coupling methods, which have been in high demand in industry for years. Cross-coupling reactions combine two different starting materials with the aid of a metal catalyst. Some reactions may lead to multiple products (e.g. ones that are mirror images of each other). Asymmetric reactions produce unequal proportions of the possible products.

Such methods provide access to compounds that are normally inaccessible and have the potential to become part of the standard repertoire in the synthesis of complex molecules.

An EPSRC IAA project built on previous EPSRC-funded research to demonstrate the scalability of their methods, and to synthesise the drug candidate Niraparib. Niraparib has shown great potential in anti-tumoral activity in breast and ovarian cancer. Dr Fletcher and his team were able to develop three different routes to Niraparib, each of which are shorter and more straightforward than MERCK, a US pharmaceutical company, had previously reported. The drug has recently been approved for ovarian cancer, and is in numerous phase II and III trial for other forms of cancer.

Late stage intermediates from the synthesis have been sent out for biological testing. The team aims to use these results to engage with industry and is in the early stages of developing a consulting and contract research spin-out. The spinout will aim to assist industry in developing the chemistry required for their own research projects.

Dr Fletcher and his team are currently working on larger-scale reactions and mechanistic studies of the reactions so that their efficiency can be improved and they can be applied to other target compounds. An additional major goal is to identify other targets and devise useful routes to them. The team have a patent application covering the technology, and are working with Oxford University Innovation to identify the best route to engage with end-users and partners. The ability to make new drugs and derivatives in a straightforward way will have a significant impact on the pharmaceutical industry.