Lead optimization in 12 months? True confessions of a chemistry team

In 1998 GlaxoWellcome embarked upon a new enzyme-inhibitor programme. This programme featured an aggressive timeframe of seven years, from the start o f medicinal chemistry through to drug launch. This period, dominated as it was by the constraints of the clinical programme, translated into a lead-op timization phase of no more than 12 months. In this article, we describe ou r attempts to meet this target, examining not only what we did and what wor ked, but also what didn't work and, most importantly, what we learnt as a r esult. At a time of considerable upheaval and challenge to the traditional model of drug discovery, we hope our experiences might stimulate interest, empathy and further discussion.