Compound optimization through data set-dependent chemical transformations

We have searched for chemical transformations that improve drug development-relevant properties within a given class of active compounds, regardless of the compounds they are applied to. For different compound data sets, varying numbers of frequently occurring data set-dependent transformations were identified that consistently induced favorable changes of selected molecular properties. Sequences of compound pairs representing such transformations were determined that formed pathways leading from unfavorable to favorable regions of property space. Data set-dependent transformations were then applied to predict a series of compounds with increasingly favorable property values. By database searching the desired biological activity was detected for several designed molecules or compounds that were very similar to these molecules. Taken together our findings indicate that data set-dependent transformations can be applied to predict compounds that map to favorable regions of molecular property space and retain their biological activity.