Table 1.
Physical parameters, metabolic stability, efflux, and toxicity of select compounds
| Cmpd | ClogP1 | tPSA | pKa | Protein binding |
Papp 10−6cs/s A to B2 |
Papp 10−6cs/s B to A3 |
Efflux ratio4 |
Microsomes5 CLint4 mL / min/mg |
Cell toxicity6 |
|---|---|---|---|---|---|---|---|---|---|
| 1 | 3.15 | 66.34 | - | 99.2% | 42.9 | 28.7 | 0.7 | 0.452 | >10 µM |
| 2 | 3.48 | 75.57 | - | 99.8% | 34.8 | 30.6 | 0.9 | 0.281 | >10 µM |
| 10 | 3.41 | 75.57 | - | 98.4% | 15.0 | 14.6 | 1.0 | 1.240 | >10 µM |
| 13 | 2.57 | 87.6 | 10.4 | 73.5% | 1.07 | 9.58 | 8.9 | 0.019 | >10 µM |
| 24 | 3.0 | 87.6 | 7.1 | 88.3% | 22.8 | 21.2 | 0.9 | 0.694 | >10 µM |
| 18 | 3.25 | 78.37 | 10.4 | 87.5% | 2.76 | 25.6 | 9 | 0.072 | >10 µM |
| 28 | 3.57 | 78.37 | 7.1 | 91.8% | 27.1 | 25.3 | .9 | 0.887 | >10 µM |
1
Determined in Chemdraw Ultra 12.0, PerkinElmer Informatics
Apparent permeability (Papp), apical to basolateral (A-B)
2
Apparent permeability (Papp) basolateral to apical (B-A)
3
Papp (B to A) / Papp (A to B)
4
CIIint = k/P, where k is the elimination rate constant and P is the protein concentration in the assay
5
Mouse liver microsomes
6
Inhibition of replication of human HFF cells