In silico ADME data from QikProp v.3.5 software (Schrödinger) for the most active multitarget lead compounds and donepezil.
Compound | Molecular volumea | QPlogPo/wb | QPlogSc | QPlogHERGd | QPlogBBe | QPlogKhsaf | QPPMDCKg | QPlogKph | CNSi | % human oral absorptionj | Human oral absorptionk |
---|---|---|---|---|---|---|---|---|---|---|---|
PQM 183 | 1229.953 | 2.12 | −2.935 | −5.602 | −0.31 | −0.443 | 240.718 | −4.257 | 1 | 77.158 | 3 |
PQM 184 | 1174.164 | 2.41 | −4.341 | −4.782 | −0.847 | −0.253 | 311.285 | −2.566 | −1 | 88.877 | 3 |
PQM 185 | 1098.222 | 1.099 | −2.858 | −4.726 | −1.036 | −0.874 | 186.166 | −2.893 | −2 | 77.51 | 3 |
PQM 186 | 1158.1 | 2.588 | −4.498 | −4.783 | −0.663 | −0.299 | 767.407 | −2.535 | 0 | 89.921 | 3 |
PQM 187 | 1253.102 | 1.603 | −2.212 | −5.572 | −0.561 | −0.619 | 90.962 | −4.185 | 1 | 74.139 | 3 |
PQM 188 | 1220.948 | 2.04 | −2.814 | −5.573 | −0.318 | −0.469 | 223.94 | −4.254 | 1 | 76.695 | 3 |
PQM 189 | 1101.684 | 1.077 | −2.822 | −4.66 | −1.084 | −0.864 | 160.269 | −3.009 | −2 | 76.299 | 3 |
PQM 190 | 1189.395 | 1.345 | −3.818 | −4.831 | −1.937 | −0.518 | 30.981 | −4.275 | −2 | 66.051 | 3 |
Donepezil | 1266.695 | 4.368 | −4.477 | −6.608 | 0.189 | 0.569 | 485.175 | −2.921 | 100 | 3 | |
Value of reference (VR) | 500.0–2000.0 | −2–6.5 | −6.5–0.5 | <−5 (not good) | −3–1.2 | −1.5–1.5 | <25 poor, >500 great | −8.0–−1.0 | −2–+2 | <25% is low | −1.5–1.5 |
Total solvent-accessible volume in cubic angstroms using a probe with a 1.4 Å radius.
Predicted octanol/water partition coefficient.
Predicted aqueous solubility, log S. S in mol dm−3 is the concentration of the solute in a saturated solution that is in equilibrium with the crystalline solid.
Predicted IC50 value for blockage of HERG K+ channels.
Predicted brain/blood partition coefficient. Note: QikProp predictions are for orally delivered drugs; for example, dopamine and serotonin are CNS negative because they are too polar to cross the blood–brain barrier.
Prediction of binding to human serum albumin.
Predicted apparent MDCK cell permeability in nm s−1. MDCK cells are considered to be a good mimic for the blood–brain barrier. QikProp predictions are for non-active transport.
Predicted skin permeability, log Kp.
Predicted central nervous system activity on a −2 (inactive) to +2 (active) scale.
Predicted human oral absorption on 0 to 100% scale.
Predicted qualitative human oral absorption: 1, 2, or 3 for low, medium, or high.