Biologically Relevant Chemical Space Navigator: From Patent and Structure–Activity Relationship Analysis to Library Acquisition and Design

A new and versatile visualization tool, based on a descriptor
accounting
for ligand–receptor interactions (LiRIf), is introduced for
guiding medicinal chemists in analyzing the R-groups from a congeneric
series. Analysis is performed in a reference-independent scenario
where the whole biologically relevant chemical space (BRCS) is represented.
Using a real project-based data set, we show the impact of this tool
on four key navigation strategies for the drug discovery process.
First, this navigator analyzes competitors’ patents, including
a comparison of patents coverage and the identification of the most
frequent fragments. Second, the tool analyzes the structure–activity
relationship (SAR) leading to the representation of reference-independent
activity landscapes that enable the identification not only of critical
ligand–receptor interactions (LRI) and substructural features
but also of activity cliffs. Third, this navigator enables comparison
of libraries, thus selecting commercially available molecules that
complement unexplored spaces or areas of interest. Finally, this tool
also enables the design of new analogues, which is based on reaction
types and the exploration purpose (focused or diverse), selecting
the most appropriate reagents.