Compound diversity, as illustrated in Figure Figure presents a 2D visual representation of the chemical space based on molecular structures, using Tanimoto's coefficient (MACCS keys, 166-bits) to visualize the structural expansion of 1000 randomly selected compounds from each designed library. The overlap between INDDS, DIADS, and PYRDS with STADS indicates that transformation rules expand the structural space from parent compounds 2-4. Furthermore, the PMI plot confirmed that the molecular shape of the generated compounds is mostly preserved, exhibiting a preference for rod and disk-like shapes, consistent with STADS in Figure . In Figure , the similarity principle was applied to each focused library relative to parent structures 2-4, which were used to expand the chemical space via transformation rules. Additionally, ppIC50 values obtained using SVR, RR, and RFR were compared to assess the linear relationship between ML model predictions (Xaxis) and the structure similarity (Y-axis). The INDDS library (first row in Figure ), where the Pearson correlation between similarity scores and ppIC50 was 0.38 for SVR and 0.41 for RR. A stronger correlation of 0.64 was observed for RFR, indicating a higher relationship between ppIC50 predictions and structure similarity.