TABLE 4.
Region 3 SAR studies
 |
Piperidine Substitution | R | Hα4β2 nAChRs |
Hα3β4 nAChRs |
||
|---|---|---|---|---|---|---|
| IC50 Value (μM)a | nH | IC50 Value (μM)a | nH | |||
| KAB-18 | 3-position, racemic |  |
13.5 (9.7–18.5) | −0.7 | NA | |
| PPB-12 | 3-position, (S)-enantiomer |  |
17.5 (10.9–28.3) | −1.0 | NA | |
| PPB-13 | 3-position, (R)-enantiomer |  |
9.8 (4.4–21.6) | −0.9 | NA | |
| IB-2 | 3-position, (S)-enantiomer |  |
10.5 (7.2–14.8) | −0.8 | 10.9 (5.1–23.3) | −0.9 |
| IB-4 | 3-position, (R)-enantiomer |  |
9.0 (4.3–14.0) | −0.9 | 9.5 (5.0–17.7) | −0.9 |
| COB-4 | 4-position, racemic |  |
8.1 (2.1–30.7) | −0.8 | 10.5 (7.6–14.4) | −0.9 |
nH, Hill coefficient; NA, no activity at concentrations up to 100 μM.
a
Values represent geometric means (confidence limits), n = 4–8.