Table 2. Potency of Sulfonamide Tethered (Hetero)aryl ethylidenes at h-P2X2R, h-P2X4R, h-P2X5R, and h-P2X7R.
| compound | R-substitution | h-P2X2 IC50 ± SEMa/% inhibition | h-P2X4 IC50 ± SEMa/% inhibition | h-P2X5 IC50 ± SEMa/% inhibition | h-P2X7 IC50 ± SEMa/% inhibition |
|---|---|---|---|---|---|
| 6a | -H | >50 (20%)b | >50 (46%)b | >50 (20%)b | 4.21 ± 0.01 |
| 6b | 2-F | 1.91 ± 0.03 | >50 (40%)b | >50 (16%)b | 2.48 ± 0.10 |
| 6c | 3-Br | >50 (0%)b | >50 (24%)b | >50 (0%)b | 5.54 ± 0.05 |
| 6d | 4-Cl | >50 (15%)b | >50 (18%)b | >50 (42%)b | >50 (48%)b |
| 6e | 4-Br | 3.22 ± 0.05 | >50 (0%)b | >50 (10%)b | >50 (34%)b |
| 6f | 4-I | 3.52 ± 0.07 | >50 (32%)b | >50 (21%)b | 10.01 ± 0.07 |
| 6g | 4-OCH3 | 3.48 ± 0.04 | >50 (45%)b | >50 (26%)b | 2.09 ± 0.13 |
| 6h | 4-NH2 | 0.32 ± 0.01 | >50 (34%)b | >50 (10%)b | 1.10 ± 0.21 |
| 7a | -H | 1.57 ± 0.01 | >50 (24%)b | >50 (29%)b | >50 (45%)b |
| 7b | 3-CH3 | 1.80 ± 0.02 | >50 (8%)b | >50 (12%)b | >50 (47%)b |
| 7c | 4-CH3 | 1.59 ± 0.01 | 3.89 ± 0.05 | >50 (31%)b | 8.94 ± 0.01 |
| 7d | 5-CH3 | 2.03 ± 0.04 | 3.21 ± 0.01 | >50 (46%)b | 4.53 ± 0.11 |
| 7e | 3-Cl | 2.17 ± 0.02 | 1.61 ± 0.04 | >50 (27%)b | 1.70 ± 0.09 |
| 7f | 5-Cl | >50 (37%)b | 4.03 ± 0.07 | >50 (0%)b | 1.16 ± 0.03 |
| 7g | 5-NO2 | >50 (26%)b | 2.44 ± 0.10 | >50 (19%)b | 6.80 ± 0.21 |
| Suramin | 13.45 ± 0.11 | 5.64 ± 0.04 | 16.07 ± 0.5 | 33.21 ± 0.47 | |
| PPADS | 1.40 ± 0.10 | 5.25 ± 0.30 | 7.01 ± 0.12 | >50 (34%)b | |
| RB-2 | 0.89 ± 0.41 | ndc | ndc | 2.79 ± 0.22 |
a
n = 3 unless otherwise noted.
b
Percent inhibition at 50 μM test compound concentration.
c
nd, not determined.