A conceptual framework for analysing and planning synthetic approaches to diverse lead-like scaffolds

Historically, chemists' exploration of chemical space has been exceptionally uneven and unsystematic. This feature article outlines a comprehensive conceptual framework that may be used to capture, analyse and plan synthetic approaches that may address this historically uneven exploration. Illustrative examples of synthetic approaches that target, or have potential to target, broad tracts of lead-like chemical space are presented within the context of this conceptual framework. Particular emphasis is placed on synthetic approaches that enable the combinatorial variation of molecular scaffold, particularly within the boundaries of lead-like chemical space.