Table 4. Diastereoisomers of Compound 16.
| compd | Cavα2δ-1 (Ki, nM)a | CYP3A4 inhibition (%)b |
|---|---|---|
| 16RR | 6 ± 9 | 46 |
| 16RS | 27 ± 8 | 56 |
| 16SR | >1000c | 15 |
| 16SS | >1000c | 44 |
a
Binding affinity (Ki, nM) in human α2δ-1 enriched membranes from hamster tumor CHO-K1 cells (Human Cav2.2/β3/α2δ1 Calcium Channel Cell Line, ChanTest) using [3H]-gabapentin as the radioligand. Each value is the mean ± SD of two determinations.
b
Percentage of inhibition after incubation at 1 μM with recombinant human CYP3A4 using BFC (7-benzyloxy-4-trifluoromethylcoumarin) as the CYP probe substrate and fluorescence detection.
c
Less than 50% inhibition at 1 μM.