Table 1. The effect of alkyl ester and tetrahydrobenzothiophene ring substitutions on the potency and efficacy of EU1794 analogues.
 |
EC50 (µM) [conf. int.]* Maximal Degree of Modulation (% of control)† |
||||||
|---|---|---|---|---|---|---|---|
| Compound | R1 | R1 volume (Å3) | R2 | GluN2A | GluN2B | GluN2C | GluN2D |
| EU1794-4 | Et | 45.15 | H | 2.2 [1.8, 2.8] 32 ± 3% |
2.6 [1.4, 4.8] 67 ± 4% |
0.42 [0.28, 0.61] 52 ± 2% |
0.36 [0.29, 0.45] 51 ± 3% |
| EU1794-2 | Et | 45.15 | Me | 0.60 [0.44, 0.82] 6 ± 2% |
1.2 [0.8, 1.9] 10 ± 3% |
0.26 [0.21, 0.31] 14 ± 1% |
0.20 [0.17, 0.25] 14 ± 1% |
| EU1794-5 | iPr | 62.16 | H | 18 [9.0, 36] 36 ± 5% |
2.5 [1.4, 4.4] 71 ± 4% |
4.0 [3.5, 4.6] 140 ± 3% |
9.3 [8.1, 11] 169 ± 7% |
| EU1794-19 | iPr | 62.16 | Me | 1.1 [0.5, 2.3] 19 ± 6% |
1.1 [0.9, 1.3] 43 ± 2% |
0.74 [0.57, 0.96] 32 ± 3% |
0.43 [0.32, 0.59] 46 ± 2% |
| EU1794-27 | tBu | 79.23 | H | 7.4 [5.3, 10] 52 ± 7% |
1.4 [1.2, 1.7] 130 ± 3% |
2.8 [2.5, 3.2] 230 ± 10% |
2.4 [1.8, 3.3] 250 ± 8% |
| EU1794-25 | Bn | 98.87 | H | - | 1.0 [0.9, 1.2] 220 ± 13% |
0.77 [0.56, 1.0] 180 ± 12% |
1.0 [0.95, 1.1] 250 ± 19% |
| EU1794-29 | n-Bu | 79.12 | H | 3.7 [1.7, 8.0] 59 ± 5% |
1.4 [1.1, 1.8] 140 ± 3% |
3.8 [2.6, 5.7] 130 ± 7% |
5.7 [5.1, 6.4] 166 ± 8% |
*EC50 values for potentiation of responses to saturating glutamate and glycine (100 μM, 30 μM) were obtained by least-squares fitting of data from individual experiments by the Hill equation. EC50 values are given as the mean with the 95% confidence interval determined from log(EC50).
†The maximal degree of modulation is given as mean ±SEM. For all compounds, data are from 4 to 18 oocytes recorded in at least two independent experiments. Data were not fit (shown as -) if the response recorded at 30 µM of test compound did not differ by more than 15% from control.