Table 2. Predicted Pharmacokinetic Features of Compounds 1–7.
| property or descriptor | compounds |
||||||
|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | |
| #starsa | 1 | 1 | 0 | 1 | 0 | 1 | 1 |
| SASAa | 550.423 | 555.464 | 562.756 | 556.539 | 544.084 | 560.778 | 560.767 |
| CIQPlogSa | –5.439 | –6.351 | –5.058 | –4.948 | –5.023 | –4.948 | –4.948 |
| QPlogPo/wa | 3.913 | 3.990 | 3.514 | 3.992 | 3.709 | 4.016 | 4.016 |
| QPPCacoa | 2000.708 | 2000.703 | 2000.027 | 3633.470 | 2306.835 | 3641.325 | 3641.106 |
| QPlogBBa | –0.180 | –0.169 | –0.417 | –0.102 | –0.279 | –0.104 | –0.104 |
| QPPMDCKa | 2580.268 | 2774.474 | 1046.488 | 1995.223 | 1221.034 | 1999.885 | 1999.755 |
| QPlogKhsaa | 0.361 | 0.384 | 0.257 | 0.316 | 0.370 | 0.333 | 0.333 |
| human oral absorption %a | 100.000 | 100.000 | 100.000 | 100.000 | 100.000 | 100.000 | 100.000 |
| rule of fiveb | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| rule of threeb | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
#stars: number of property or descriptor values that fall outside the 95% range of similar values for known drugs (recommended range: 0–5). SASA: total solvent accessible surface area in square angstroms using a probe with a 1.4 Å radius (recommended range: 300.0–1000.0). CIQPlogS: conformation-independent predicted aqueous solubility (recommended range: −6.5 to 0.5). QPlogPo/w: predicted octanol/water partition coefficient (recommended range: −2.0 to 6.5). QPPCaco: predicted apparent Caco-2 cell permeability in nm/s (<25 poor, >500 great). QPlogBB: predicted brain/blood partition coefficient (recommended range: −3.0 to 1.2). QPPMDCK: predicted apparent MDCK cell permeability in nm/s (<25 poor, >500 great). QPlogKhsa: prediction of binding to human serum albumin (recommended range: −1.5 to 1.5). Human oral absorption %: predicted human oral absorption on a 0 to 100% scale (>80% is high, <25% is poor).
Rule of five: number of violations of Lipinski’s rule of five. The rules are molecular weight of the molecule <500, QPlogPo/w < 5, hydrogen bond donor atoms ≤5, hydrogen bond acceptor atoms ≤10. Compounds that provide these rules are considered drug-like molecules (maximum is 4). Rule of three: number of violations of Jorgensen’s rule of three. The three rules are predicted aqueous solubility (QPlogS) > −5.7, predicted apparent Caco-2 cell permeability (QPPCaco in nm/s) > 22 nm/s, #primary metabolites <7 (maximum is 3). Compounds with fewer (and preferably no) violations of these rules are more likely to be orally available agents (Schrödinger Release 2022-2, LLC, New York, USA).