Table 3. Safety and in Vitro Pharmacokinetic Profile of Compound 11.
| CYP Inhibition Assaya (IC50, μM) | |
| 1A2 | 81.13 ± 13.26 |
| 2C9 | 17.02 ± 3.67 |
| 2C19 | 23.06 ± 1.96 |
| 2D6 | 32.58 ± 7.40 |
| 3A4 | 27.84 ± 1.92 |
| Cardiotoxicity (IC50, μM)b | |
| hERG ligand binding assay | 8.78 (n = 3) |
| hERG K+ channel activity assay | 10.9 (n = 3) |
| Liver Microsomal Phase I Stabilityc | |
| Rat (%) | 49.18 ± 2.8 |
| Human (%) | 50.24 ± 5.88 |
| Rat (t1/2, min) | 28.88 ± 0.72 |
| Plasma Stability (%)d | |
| Rat (%) | 90.10 ± 4.78 |
| Human (%) | 71.87 ± 2.20 |
| Plasma Protein Binding (%)e | |
| Rat (%) | 98.67 ± 0.09 |
| Human (%) | 99.27 ± 0.07 |
a
IC50 values (μM) in human liver microsomes using cocktail substrate assay (mean ± SD, n = 3).
b
See Supporting Information (p 8) for this part.
c
Liver microsomal phase I stability (% of remaining after 30 min), (mean ± SD, n = 3).
d
Experiment about percentage of remaining after 4 h incubation at 37 °C, (mean ± SD, n = 3).
e
Plasma protein binding rate (%) (mean ± SD, n = 3).