The concept of activity cliffs has gained popularity as a means to identify and understand discontinuous SAR, i.e., regions of SAR where minor changes in structure have unpredictably large effects on biological activity. To the best of our knowledge, activity cliffs have been invariably evaluated using global measures of molecular similarity that do not take into account the presence of finer substructure among a series of related analogs. In this talk, we look at activity cliffs within a congeneric series, by decomposing them into R-groups and analyzing how activity is affected by changes in a single variation site. The analysis is greatly enhanced by R-group-aware visualization tools such as the SAR maps, which have been enhanced to specifically highlight such discontinuities.

R-Cliffs: Activity cliffs within a single analog series

240th National Meeting (2010)

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