Table 3. Physicochemical and in Vitro Profiles of 13 and 19.
| property/assaya | 13 | 19 |
| MWt | 372.4 | 440.3 |
| clog P | 3.49 | 4.38 |
| CHI | 3.83 | 4.25 |
| Pf IC50 (μM) | 0.066 | 0.003 |
| cP450b (μM) | >10c | >10d |
| hERGe (μM) | >50 | >50 |
| CLND solubilityf (μM) | 100 | 9 |
| permeability (nM/s) | 240 | |
| mouse ppbg (%) | 99.0 | 99.4 |
| human ppb (%) | 99.0 | |
| cross-screening | inactive in 44/45 assaysh | inactive in 43/45 assaysi |
a
See previous tables for definitions of abbreviations.
b
P450s tested were 2C9, 2C19, 2D6, and 3A4.
c
Except for 2C9 7.9 μM.
d
Except for 2C9 6.3 μM.
e
Dofetilide binding assay.
f
Chemiluminescent nitrogen detection—a turbimetric assay from DMSO solution.
g
Ppb is a plasma protein binding.
h
A 2.5 μM activity observed against the PXR receptor.
i
A 0.3 and 1 μM activity observed against PDE4B and the PXR receptor.