Table 2.
ADME/T properties of the ligands in comparison to reference molecules, interpreting pharmacological parameters and Lipinski's rule predicted using QikProp module of Schrödinger.
| Table 2A. ADME/T properties | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Compound | MW | dipole | SASA | FOSA | FISA | PISA | WPSA | volume | DonorHB | AccptHB | % HOA | RO5 | |||
| MB_183 | 396.57 | 0 | 557.49 | 449.09 | 108.40 | 0 | 0 | 1081.89 | 8 | 12.4 | 15.95 | 1 | |||
| MB_241 | 406.61 | 0 | 610.37 | 492.15 | 118.21 | 0 | 0 | 1211.44 | 4 | 11.2 | 58.57 | 0 | |||
| MB_250 | 469.62 | 0 | 528.52 | 413.29 | 115.22 | 0 | 0 | 1130.50 | 7 | 14.2 | 24.37 | 1 | |||
| MB_266 | 423.42 | 0 | 591.19 | 218.28 | 271.33 | 0 | 101.5 | 1103.16 | 10 | 8.7 | 0 | 1 | |||
| MB_380 | 1363.78 | 0 | 1328.07 | 472.39 | 852.84 | 0 | 2.8 | 2976.54 | 29 | 18.8 | 0 | 3 | |||
| Boceprevir | 529.76 | 0 | 809.27 | 639.60 | 169.67 | 0 | s0 | 1634.66 | 10 | 13.8 | 4.47 | 2 | |||
| N3 inhibitor | 694.91 | 0 | 1100.84 | 902.28 | 198.56 | 0 | 0 | 2205.81 | 4.75 | 15.65 | 4.372 | 3 | |||
| Table 2B. ADME/T properties | |||||||||||||||
| Compound | QPlogPo/w | QPlogS | CIQPlogS | QPPCaco | QPlogBB | QPPMDCK | QPlogKp | PSA | QPlogKhsa | ||||||
| MB_183 | −3.206 | 2 | 3.861 | 14.409 | 0.014 | 6.85 | −6.87 | 93.51 | −0.647 | ||||||
| MB_241 | 0.3 | −0.077 | −0.967 | 46.632 | −0.154 | 22.035 | −6.95 | 76.50 | −0.391 | ||||||
| MB_250 | −1.569 | 1.869 | 0.031 | 12.414 | 0.099 | 5.831 | −7 | 104.17 | −0.448 | ||||||
| MB_266 | −3.332 | 2 | 2.743 | 0.411 | −1.244 | 0.527 | −9.87 | 134.99 | −0.676 | ||||||
| MB_380 | −4.811 | 2 | −8.657 | 0 | −11.359 | 0 | −17.042 | 502.64 | −1.735 | ||||||
| Boceprevir | −1.177 | 2 | 1.761 | 3.781 | −1.49 | 1.613 | −6.852 | 132.55 | −0.686 | ||||||
| N3 inhibitor | 1.084 | −3.085 | −2.254 | 3.601 | −2.173 | 3.308 | −7.48 | 220.99 | −0.792 | ||||||
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), logP o/w = log P for octanol/water (−2.0/6.5), dipole = Dipole Moment (1.0/12.5), logS = log S for aqueous solubility (−6.5/0.5), SASA = Total solvent accessible surface area (300.0/1000.0), CIlogS = log S - conformation independent (−6.5/0.5), FOSA =Hydrophobic solvent accessible surface area (0.0/750.0), logBB = 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/hr), 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 (+-20%) (<25% is poor), volume = Molecular Volume (A∧3) (500.0/2000.0), Apparent Caco-2 Permeability (nm/sec) (<25 poor,>500 great), donorHB = Donor - Hydrogen Bonds (0.0/6.0), Apparent MDCK Permeability (nm/sec) (<25 poor,>500 great).