Focussed and Targeted Library Design: an example using the SEAL method

When searching for active analogs of a lead-compound a balance between similarity and diversity is often needed. Assessing the similarity by molecular fingerprint will often result in topologically closely related compounds. With our 3D electronic descriptor based SEAL method we can identify functionally equivalent but chemically very diverse compounds. The SEAL method also allows for matching of substructures. Below is an example of a tuneable library where a number of 1-step reaction products is ranked by 3-D similarity to the lead in the lower left corner. The rows and columns show the synthesis starting materials.


targeted library design example
An example of a (very small) library with a defined similarity relationship to a chosen target. The target is depicted in the lowerleftcorner. Only the target molecule is needed for the design process. The reactants as well as reactions that constitute a library are automatically generated.



virtual hight throughput screening example
Similarity of a part of one of the relevant chemical spaces to the target molecule. Various libraries can be extracted from the chemical spaces uncovered; this space was used to extract the library exemplified in the figure above. The virtual reaction products are coloured according to similarity, red denoting the highest similarity score.