UK pharmaceutical chemists reveal significant gaps in drug making processes worldwide. 

John Carey from pharmaceutical firm GlaxoSmithKline, UK, and colleagues from drug companies AstraZeneca, UK, and Pfizer, UK, carried out a survey on the syntheses of 128 drug candidates in early development in the process chemistry research and development departments of the three companies.  The study covered all therapeutic and geographic areas in which the companies have interests. The survey revealed that the three companies were taking surprisingly similar approaches to drug development, said Carey.

Common reactions for making drug candidates are based on discoveries made many years ago and often involve unnecessarily complicated multi-step processes, according to Carey's team. Carey and colleagues recognised potential for improvement in several reactions, for example, new alkylating agents could be used, chemoselectivity could be improved for modifying reactions, and a mild catalytic hydrogenation could be developed to effect certain reduction transformations. 

Paul Clarke, senior lecturer in organic chemistry at the University of York, UK, is experienced in the synthesis of biologically active molecules. 'One fifth of all reactions are heteroatom alkylations or arylations and a further 12% are acylations' said Clarke. 'This simply leads to the same types of molecules being prepared as drug candidates by each company. One wonders if a change of strategy is not urgently required if progress is to be made in the treatment of disease in the next 100 years.' 

Pharmaceutical manufacturing processes are subjected to strict regulations. These regulations govern product quality, patient safety and environmental considerations, and influence the synthetic routes chosen by drug companies. This is likely to be a challenge to future research in the area, said Carey.   

'The long term goal would be to have catalytic methods developed to carry out the common transformations,' said Carey. He suggests this survey will 'act as a stimulus to researchers wishing to develop methods that would have general application in the area of pharmaceutical synthesis'. 

Katherine Vickers