Table 1. In Vitro Drug Property Analyses of 1 and 2.
| assay (conditions) | 1 | 2 |
|---|---|---|
| aqueous solubilitya | 3.1 ± 0.2 μM | 136 ± 0.9 μM |
| partition coefficientb | 3.25 | 3.84 |
| plasma protein bindingc | 95.3 ± 3.1% bound; 93.3 ± 24.0% recovery | 99.2 ± 0.9% bound; 99.8 ± 5.5% recovery |
| A-B permeabilityd | <0.7 ± 0.04 ×10–6 cm/s; 14% recovery | 8.3 ± 0.4 × 10–6 cm/s; 20% recovery |
| B-A permeabilityd | ncg | 0.7 ± 0.1 × 10–6 cm/s; 46% recovery |
| metabolic stability (liver)e | 79 ± 13.6% parent remaining | 49 ± 1.3% parent remaining |
| metabolic stability (intestine)f | ncg | 86 ± 7.0% parent remaining |
a
PBS, pH 7.4.
b
log D, n-octanol/PBS, pH 7.4, 1.0 × 10–4 M, weighted average of 3 trials.
c
CD-1 mouse, test at 1.0 × 10–5 M.
d
Caco-2, pH 6.5/7.4, 1.0 × 10–5 M.
e
liver microsomes, CD-1 mouse, 1.0 × 10–6 M, 60 min.
f
Intestinal microsomes, CD-1 mouse, 1.0 × 10–6 M, 60 min.
g
nc = not calculated.