Current fragment sets tend to be dominated by flatter molecules, and their shape diversity does not reflect that of the fragments that are theoretically possible. The design and synthesis of a set of bridged fragments containing a bridgehead nitrogen is described. Many of these fragments contain twisted lactams whose modulated electronic properties may present unusual opportunities for interaction with target proteins. The demonstrated novelty, three-dimensionality and molecular properties of the set of 22 fragments may provide valuable, and highly distinctive, starting points for fragment-based drug discovery
