Factors Determining the Selection of Organic Reactions by Medicinal Chemists and the Use of These Reactions in Arrays (Small Focused Libraries)

Synthetic organic reactions are a fundamental enabler of small-molecule drug discovery, and the vast majority of medicinal chemists are initially trained-either at universities or within industry-as synthetic organic chemists. The sheer breadth of synthetic methodology available to the medicinal chemist represents an almost endless source of innovation. But what reactions do medicinal chemists use in drug discovery? And what criteria do they use in selecting synthetic methodology? Why are arrays (small focused libraries) so powerful in the lead-optimization process? In this Minireview, we suggest some answers to these questions and also describe how we have tried to expand the number of robust reactions available to the medicinal chemist. Helping chemists help chemists: What reactions do medicinal chemists use in drug discovery? (The pie chart shows a snapshot from one unit at GlaxoSmith-Kline.) What criteria do they use to select synthetic methodology? Why are arrays (small focused libraries) so powerful in the lead-optimization process? These questions are considered in this Minireview, which also describes attempts to expand the number of robust reactions available to medicinal chemists. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.