Table 2.
Affinity or Potency of Various Adenosine Derivatives at Human Adenosine Receptors
| Compounda | hA1 Binding Ki(nM) b | hA2A Binding Ki(nM) c | hA2A Activation % c | hA2B Activation EC50d | hA3 Binding Ki(nM) c |
|---|---|---|---|---|---|
| 3 | 6.8 ± 2.4 | 2.2 ± 0.6 | 100 | 140 ± 19 (n = 4) | 16.0 ± 5.4 |
| 5 | 775 ± 235 | >100,000 | 32.9 ± 2.0 | >10,000 | 24,600 ± 8,200 |
| 6 | 7.0 ± 1.0 | 628 ± 39 | 102 ± 4 | 54.5 ± 13.3 | 5.1 ± 1.3 |
| 7 | 171 ± 15 | 2,230 ± 330 | 92.2 ± 1.0 | 12,000 ± 4200 | 378 ± 33 |
| 1 | 245 ± 48 | 3,120 ± 370 | 90.3 ± 1.4 | 15,600 ± 2,800 | >100,000 |
| 8 | >100,000 | >10,000 | 51.0 ± 7.6 | >10,000 | >10,000 |
| 9 | >100,000 | >100,000 | 11.6 ± 4.6 | >10,000 | >10,000 |
| 10 | >100,000 | >100,000 | 0 | >10,000 | >100,000 |
| 11 | 12.8 ± 3.1 | 505 ± 30 | 84.5 ± 3.4 | 942 ± 38 | 9450 ± 1760 |
| 12 | >10,000 | >10,000 | 78.9 ± 4.5 | >100,000 | 394 ± 74 |
| 13 | 106 ± 30 | 5430d | 108 ± 3 | >1000 | 78.8 ± 25.5 |
| 14 | >10,000 | 55,900 ± 4,600 | 91.4 ± 5.2 | >1,000 | >10,000 |
| 15 | 368 ± 147 | >10,000 | 102 ± 2 | 3,720d | 1,640 ± 400 |
| 16 | 39.3 ± 8.3 | 764 ± 105 | 112 ± 6 | ND | 47.2 ± 10.8 |
| 17 | 484 ± 22 | >10,000 | 93.3 ± 5.5 | >10,000 | 39.0 ± 2.4 |
| 18 | >10,000 | >10,000 | 42.2 ± 1.3 | >10,000 | 719 ± 37 |
| 19 | >10,000 | >10,000 | 2 | >10,000 | 2,730 ± 268 |
n = 3, unless noted. ND, not determined.
a
Structures shown in Table 1. 1, MRS3366; 3, NECA; 6, MRS3218; 7, MRS3412; 11, MRS3407; 14, MRS3417.
b
Binding experiments carried out for various subtypes of human recombinant adenosine receptors stably expressed in mammalian cells using the following radioligands (concentration): hA1 (CHO cells), [3H]R-PIA (2.0 nM); hA2A (HEK-293 cells), [3H]CGS21680 (15 nM); hA3 (CHO cells), [125I]I-AB-MECA (0.5 nM).
c
At hA2A and hA2B receptors expressed in CHO cells, cAMP was measured. For hA2A receptors, values are expressed as percent stimulation of cyclic AMP production at 100 μM (value for NECA is 100%).
d
n = 1.