Table 1. Structure-Activity Relationships.
| Compound | μM[a] | % Block[b] | Active Isomer |
|---|---|---|---|
| 1 (AAQ) | 400 | >95 | trans |
| 2 (MAQ) | 400[c] | 0 | - |
| 3 | 1000 | >95 | trans |
| 4 | 800 | >95 | trans |
| 5 | 300 | >95 | trans |
| 6 | 200 | >95 | trans |
| 7 (BzAQ) | 25 | >95 | trans |
| 8 | 2000 | 0 | trans |
| 9 | 1000 | ND[d] | trans = cis |
| 10 (PrAQ) | 40 | ∼50 | cis |
Concentrations reported for 1-6 & 8 were determined by first identifying a dose producing >95% block. We then reduced the concentration in 100 μM increments until <95% block was observed. For compounds 7 and 10, 5 μM increments identified the reported values. At each reported concentration, determinations were repeated in 3-5 cells from two separately treated coverslips.
For compounds 1-9, % Block was calculated as the % of Iss measured at 380 nm that was blocked at 500 nm. For compound 10, the wavelengths were reversed. In each case, unblock was estimated as complete by the lack of open-channel block, as shown in Figure 5 of the Supporting Information.
Treatment of HEK293 cells with MAQ at concentrations >400 μM did not afford stable recordings.
Although substantial open-channel block was observed, the lack of unblock at either wavelength prevented calculation of % Block.