Directed R-Group Combination Graph: A Methodology To Uncover Structure–Activity Relationship Patterns in a Series of Analogues
Anne Mai Wassermann, Jürgen Bajorath · Journal of Medicinal Chemistry · 2012
A graphical method is introduced to study details of structure-activity relationships (SARs) in analogue series that further extends conventional analysis of analogues using R-group tables or related approaches and that provides additional and more differentiated SAR information. The newly designed graph structure represents entire series of analogues in a consistent manner, regardless of their size and complexity of substitution patterns. The approach is specifically tailored toward a systematic exploration and intuitive interpretation of SAR features involving different R-groups and their combinations. Analogues and their potency information are systematically organized on the basis of R-group combinations that are present in a series. This organization scheme results in graph components that represent well-defined SAR patterns. Analysis of these patterns provides an immediate access to critical substitution sites and R-group combinations, favorable and unfavorable R-groups, or nonadditive potency effects of multisite substitutions. Furthermore, the data structure makes it possible to design new analogues by combining favorable R-group combinations derived from different compounds.