Systematic mapping of R-group space enables the generation of an R-group replacement system for medicinal chemistry

Selection of R-groups (substituents, functional groups) is of critical importance for the generation of analogues during hit-to-lead and lead optimization. In the practice of medicinal chemistry, R-group selection is mostly driven by chemical experience and intuition taking synthetic criteria into account. However, systematic analyses of substituents are currently rare. In this work, we have computationally isolated R-groups from more than...