2.3.2. Chemical Space

The calculated molecular descriptors (MW (molecular weight), log *P* (water-octanol partition coefficient), HD (hydrogen bond donors), HA (hydrogen bond acceptors), PSA (polar surface area), and RB (rotatable bonds)) are given in Table S3. The log *P* values range from 4.4 and 6.3, lying between the drug-like and Known Drug Space (KDS), while the HD and PSA values are within the lead-like space (for the definition of lead-like, drug-like, and KDS regions, see [72] and Table S4). The molecular weight of the ligands is between 326.4 and 453.4 g·mol−<sup>1</sup> , falling in the drug-like chemical space. The main issue with these ligands is their relatively high lipophilicity, with Log *P* values reaching into the KDS.

The Known Drug Indexes (KDIs) of each ligand were calculated to gauge the balance of the molecular descriptor of the ligands (Table S5, Supplementary Information). This method is based on the statistical analysis of drugs in clinical use (KDS) and a weighted index for each of the six molecular descriptors used; both the summation (KDI2a) and multiplication (KDI2b) methods were used [73]. The KDI2a values range from 4.7 to 5.3, with a theoretical maximum of 6 and an average of 4.08 for known drugs. KDI2b ranges from 0.2 to 0.5, with a theoretical maximum of 1 and a KDS average of 0.18. This indicates that the majority of the ligands are well balanced. The most potent ligand **3ba** has KDI2a of 4.90 and KDI2b of 0.27, while drugs with high bioavailability (>50%) have average KDI2a of 4.43 and KDI2b of 0.21, which shows that **3ba** has a very good balance of physicochemical properties for bioavailability.
