Towards the realisation of lead-oriented synthesis

Sourcing large numbers of lead-like molecules - compounds that would serve as good starting points for drug discovery programmes - is currently very challenging. The concept of lead-oriented synthesis has recently been articulated to capture the specific problem of preparing diverse small molecules with lead-like molecular properties. In this Feature, some methods that might be used to prepare lead-like molecular scaffolds are described, and presented in the context of diversity-oriented synthetic strategies that allow wide variation in molecular scaffold. It is concluded that the development of a wider toolkit of reactions that is reliable with more polar substrates will be required to allow genuine combination of molecular scaffold within lead-like chemical space.