SOLUTION-PHASE COMBINATORIAL CHEMISTRY IN LEAD DISCOVERY

Solution-phase approaches in combinatorial chemistry complement solid- phase approaches and each can be used to advantage in particular circu mstances. Solution-phase synthesis of pools of compounds, whilst allow ing successful identification of a selection of good lead structures f or medicinal chemistry programmes, also reinforced a number of the dis advantages of such an approach. Solution-phase parallel synthesis of d iscrete compounds has, however, proved to be a very useful and popular approach both for lead generation and in lead optimisation work. The range of chemistry suitable for use in such approaches is expanding ra pidly and some of these chemistries are discussed. The current focus i s on enhancing the quality of compounds prepared in array formats, and we describe a number of useful approaches which are being developed t o that end.