Table 3.
Preliminary Pharmacokinetic Activity of PSZ and Analogues.
| Cmpd | Solubility (μM)a |
cCYP3A4 IC50 (μM) |
hERG Inhibition (%)b |
T1/2 (min)c |
Clint (μL/min/mg)c |
|---|---|---|---|---|---|
| PSZ | 0.781 | 0.15 | 14.7 | 108 ± 5.3 | 21.5 |
| ITZ | 0.8 | 0.04 | < 1 | 27.0 ± 6.2 | --- |
| 1 | --- | >20 | --- | 61.8 ± 2.1 | 37.4 |
| 19 | 1.56 | --- | --- | --- | --- |
| 21 | 0.781 | >20 | 3.6 | --- | --- |
| 28 | 3.13 | >20 | 4.2 | 115 ± 9.8 | 20.0 |
| 29 | 3.13 | --- | --- | > 180 | 2.23 |
| 30 | 1.56 | --- | --- | > 180 | 7.15 |
a
Kinetic solubility determined in PBS at pH 7.4.
b
Percent inhibition of the hERG channel at 25 μM.
c
T1/2 and Clint were measured in human liver microsomes at 1 μM.
---indicates values were not determined.