Table 5.
In Vitro ADME Profile for 35
| microsomal stability |
|||||||
|---|---|---|---|---|---|---|---|
| compd | PBS buffer (pH 7.4) solubility (µg/mL) |
T1/2 (min)a,b | T1/2 (min)a,b | permeability (1 × 10−6 cm/s) |
efflux ratio |
mouse plasma stability remaining at 2 h (%) |
PBS buffer (pH 7.4) stability at 48 h (%) |
| 35 | <5 | >30 (rat) | >300a (mouse) |
1.5 (A→B)a 394c | 1.8 | 100 | 100 |
| 36 | >60 | >30 (rat) | NT | 168c | NT | 100 | 100 |
a
These experiments were conducted at Pharmaron Inc. All other studies were conducted at NCATS.
b
Represents the stability in the presence of NADPH. 35 and 36 showed no degradation without NADPH present over a 1 h period.
c
Represents permeability in the Parallel Artificial Membrane Permeability Assay (PAMPA) at pH 7.4.