Table 5.
ADME Properties of the Selected 4-(Aminomethyl)benzamides.
| N | Metabolic stabilitya | CYP450 inhibitionb | ||||
|---|---|---|---|---|---|---|
| Plasma | Liver microsome | CYP3A4 (IC50, μM) | CYP2C9 (IC50, μM) | |||
| Human | Rat | Human | Rat | |||
| 5 | 63 | 78 | 54 | 0 | NTc | NT |
| 20 | 100 | 88 | 90 | 94 | 15.1 | 4.49 |
| 23 | 85 | 82 | 17 | 99 | >100 | 18.6 |
| 26 | 87 | 86 | 28 | 23 | NT | NT |
| 27 | 88 | 82 | 31 | 24 | NT | NT |
| 32 | 100 | 96 | 75 | 71 | >100 | >100 |
| 33 | 86 | 86 | 34 | 57 | >100d | 3.14d |
| 35 | 100 | 89 | 64 | 75 | >100d | 4.98d |
| 43 | 85 | 0 | 31 | 0 | NT | NT |
| 49 | 94 | 62 | 46 | 27 | 24.0 | 7.94 |
| 50 | 88 | 2 | 2 | 0 | NT | NT |
a
% of compound remaining after 60 min related to t0.
b
10 μM quinidine and 30 μM sulfaphenazole were used as the positive inhibitor controls in the CYP3A4 inhibition assay and the CYP2C9 inhibition assay, respectively. Results are from three replicates: errors are estimated to be <10%.
c
NT, not tested.
d
tested at Reaction Biology Corp.