The ligand library for the prospective PDE2 inhibitor study in the Part II of the manuscript was constructed around a modified core from the 4D09 PDB entry . A manual examination of the dataset explored in Part I revealed that chlorination of the cyclohexene ring at different positions and addition of a methyl or a difluoromethyl to the tricycle led to better binding affinities, a single combination of these features was chosen as the core of the current library and chemical space exploration was restricted to the remaining R-group (Fig. ). The various Rgroups were built up from fragments present in the dataset from Part I to increase the likelihood of synthetic accessibility of the ligands.