Table 2. ADME/T Properties of the Ligands Compared to Those of the Cocrystal Ligand and Interpreting ADME/T and Lipinski’s Filters Using the QikProp Module of Schrödingera.
| (A) ADME/T properties | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| compound | MW | dipole | SASA | FOSA | FISA | PISA | WPSA | volume | donorHB | accptHB | HOA |
| cocrystal ligand | 429.219 | 7.039 | 660.251 | 72.19 | 404.148 | 178.256 | 5.658 | 1098.776 | 9 | 9.1 | high |
| ZINC000000509440 | 302.843 | 2.131 | 437.358 | 252.59 | 115.998 | 0 | 68.77 | 824.153 | 4 | 6.4 | high |
| ChEMBL1236395 | 342.299 | 5.293 | 520.068 | 210.852 | 309.216 | 0 | 0 | 952.581 | 8 | 18.7 | high |
| ChEMBL2104398 | 344.315 | 4.852 | 561.224 | 244.013 | 317.211 | 0 | 0 | 987.386 | 9 | 18.7 | high |
| ChEMBL3427435 | 706.615 | 4.742 | 1158.078 | 392.293 | 553.143 | 162.421 | 50.222 | 2086.721 | 7.5 | 20 | high |
| (B) ADME/T properties | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| compound | QPlogPo/w | QPlogS | CIQPlogS | QPlogHERG | QPPCaco | QPlogBB | QPPMDCK | QPlogKp | QPlogKhsa | PSA |
| cocrystal ligand | 1.179 | –2.391 | –4.253 | 3.095 | 0.024 | –4.635 | 0.001 | –7.092 | –1.854 | 230.238 |
| ZINC000000509440 | 0.059 | –0.008 | –0.4 | –3.437 | 48.943 | 0.59 | 55.277 | –7.591 | –0.256 | 63.272 |
| ChEMBL1236395 | –3.635 | –0.983 | 0.117 | –3.146 | 11.577 | –2.703 | 3.993 | –6.066 | –1.195 | 193.968 |
| ChEMBL2104398 | –3.83 | –0.664 | 0.109 | –3.887 | 9.723 | –3.358 | 3.307 | –5.734 | –1.567 | 192.794 |
| ChEMBL3427435 | 0.898 | –3.726 | –4.237 | 4.333 | 0 | –8.811 | 0 | –8.646 | –2.562 | 358.379 |
Minimal ranges: MW = molecular weight (130.0/725.0), accPthB = acceptor—hydrogen bonds (2.0/20.0), rotor = no. of rotatable bonds (0.0/15.0), log P o/w = log P for octanol/water (−2.0/6.5), dipole = dipole moment (1.0/12.5), log S = log S for aqueous solubility (−6.5/0.5), SASA = total solvent accessible surface area (300.0/1000.0), CI log S = log S—conformation-independent (−6.5/0.5), FOSA = hydrophobic solvent accessible surface area (0.0/750.0), log BB = log BB for brain/blood (−3.0/1.2), FISA = hydrophilic solvent accessible surface area (7.0/330.0), log Kp = log Kp for skin permeability (Kp in cm/h), PISA = carbon Pi solvent accessible surface area (0.0/450.0), log Khsa = log Khsa serum protein binding (−1.5/1.5), WPSA = weakly polar solvent accessible surface area (0.0/175.0), Lipinski Rule of 5 Violations-RO5 (maximum is 4), PSA = vdW polar surface area (7.0/200.0), human oral absorption in GI (low/high) (<25% is poor), volume = molecular volume (Â3) (500.0/2000.0), apparent Caco-2 permeability (nm/s) (<25 poor, >500 excellent), donorHB = donor—hydrogen bonds (0.0/6.0), and apparent MDCK permeability (nm/s) (<25 poor, >500 excellent).