Table 2.
Predicted physicochemical and ADME descriptors for derivative 37a.
| Desidered value | 37a | |
|---|---|---|
| MWa | <500 | 361 |
| LogDb | <5 | 3.62 |
| LogSc | >1 | 1.41 |
| HBAd | <5 | 2 |
| HBDe | <10 | 1 |
| tPSA (Å2)f | <180 | 26.6 |
| Caco-2g | >–5 | −4.48 |
| HIAh | + | + |
| 2C9 pKii | <6 | 5.02 |
| Stabilityj | Stable | Stable |
a
Molecular weight.
b
Logarithm of the octanol/water partition coefficient at pH = 7.4.
c
Intrinsic aqueous solubility: logS ≥ 1 corresponds to intrinsic aqueous solubility greater than 10 µM.
d
Number of hydrogen bond acceptors.
e
Number of hydrogen bond donors.
f
Topological polar surface area.
g
Apparent permeability across monolayers of the Caco-2 line of human epithelial colorectal adenocarcinoma cells.
h
Human intestinal adsorption: classification of “+” for compounds which are ≥30% adsorbed and “−” for compounds which are <30% adsorbed.
i
pKi values for CYP2C9 affinity. The defined threshold is to avoid drug-drug interactions due to inhibition of CYP2C9.