Ring systems in medicinal chemistry: A cheminformatics analysis of ring popularity in drug discovery over time

Abstract

Rings are the most important structural component of bioactive molecules. They determine molecule shape, keep substituents in their proper positions and also influence key pharmacokinetic and pharmacodynamic properties. Heterocycles in particular are prevalent in a majority of small-molecule drugs, serving as hydrogen bond donors or acceptors and exerting conformational constraints that enhance target activity and selectivity. Advances in synthetic methodologies have greatly expanded the accessible chemical space of ring systems, enabling the rapid generation of novel interesting rings. This article explores the occurrence of various ring systems in molecules described in the medicinal chemistry literature and shows how their development and utilization has varied over time. Various factors influencing these patterns, including introduction of new synthetic methods, novel techniques and strategies applied in drug discovery and better knowledge of molecular properties affecting success of drug development candidates are discussed.

Keywords: Chemical space; Cheminformatics; Heterocyclic rings; Rings; Scaffolds.