Table 9. In Vitro Physicochemical Properties.
| parameters | 1 | 2 | 3 |
|---|---|---|---|
| structure | Lerisetron (R = H) | (R = Me) | (R = Cl) |
| molecular weighta | 292.4 | 306.4 | 326.8 |
| PSAa | 35.56 | 35.56 | 35.56 |
| cLog Pa | 3.3 | 3.8 | 4.1 |
| solubility (mM), (pH 6.8) | >1 | >0.1a | 0.77 |
| PAMPA (%FA) | 99 | 100 | 99 |
| mouseb/ratc/humanb | 29/–/26.6 | 36.7/172/43.5 | 45.3/79/<25 |
| mPPBd (%) | 93.7 | 97.8 |
a
In silico predictions; PSA = polar surface area; PAMPA = parallel artificial membrane permeability assay (fraction absorbed).
b
In vitro metabolic stability in liver microsomes (μL/(min mg)).
c
In vitro metabolic stability in hepatocytes (μL/min per 106 cells).
d
mPPB = mouse plasma protein binding.