Research

Organocatalysis

 

The devolpment of small metal-free molecules capable of catalysing chemical reaction is (in our opinion) one of the most challenging and rewarding fields in contemporary organic chemistry.

 

 

New synthetic methodology

 

We are interested in the development of new organocatalytic reactions and processes of high synthetic utility. Representative examples of recent projects are shown below.

 

 

Medicinal chemistry: anti-cancer drug design

 

Paullones are tetracyclic indole-based compounds that have been demonstrated to act as powerful cyclin-dependent kinase (CDK) inhibitors with potential anti-tumour properties. These relatively new drug candidates have yet to be fully developed as targets for anti-cancer drug design. We (in collaboration with Prof. D. H. Grayson) are engaged in the design of a range of paullone derivatives, with the dual aim of both maximising CDK1 binding selectivity and in vivo activity. A study to evaluate the inhibitory activity of these compounds against a range of kinases indentified 9-azapuallone N-oxide as a selective inhibitor of CDK9/cyclin T. The potential significance of the function of CDK9/cyclin T in a range of medicinally relevant domains such as cell cycle/transcription regulation, HIV-1 replication and cardiovascular disease is only beginning to be understood, thus the development of highly selective inhibitors of this complex is a goal of considerable interest.