’This has really heightened awareness of the need for medicinal chemists to achieve high selectivity and safety in the compounds we design.’ While one can never legislate for unexpected events in trials, there are tactics chemists can employ to ensure the compounds they put forward for development are more likely to succeed.
’The success or failure of a molecule is embodied in it when it’s made,’ Leeson says.
One explanation is that by making a compound larger to increase its affinity for a target, you also make it more lipophilic, and thus less stable in an aqueous environment.
’This is where the extra potency really comes from - [the molecule] is driven out of the water and onto the receptor.
’We can make 1000 compounds - or more - in a discovery programme, and only a few of them are actually worth making.’ Wood agrees.