Table 1. Binding Affinity of Various Known and Newly Synthesized A3AR Antagonists (Affinity at the Human Receptors, Unless Noted; m, Mouse; r, Rat)a.
| compound | A1 (Ki, nM or % at 10 μM) | A2A (Ki, nM or % at 10 μM) | A2B (Ki, nM or % at 10 μM)b | A3 (Ki, nM) |
|---|---|---|---|---|
| 6c | 35.4 ± 4.2%, 27.4 ± 2.0% (m), 25.5 ± 1.9% (r) | 16.4 ± 2.9%, 25.1 ± 8.1% (m), 7.4 ± 3.2% (r) | 34.5 ± 4.6%, 20.2 ± 5.0% (m), 38.8 ± 4.7% (r) | 43.9 ± 7.6, 349 ± 72 (m), 216 ± 65 (r) |
| 9c | 162 ± 49, 411 ± 113 (m), 333 ± 58 (r) | 121 ± 42, 830 ± 92 (m), 1150 ± 80 (r) | 230 ± 40, 189 ± 61 (m), 163 ± 23 (r) | 1.65 ± 0.57, 9.61 ± 2.27 (m), 8.53 ± 1.22 (r) |
| 16b | 78.7 ± 3.3 | 3550 | ND | 69.2 ± 11.9 |
| 16c | 1450 ± 600, 252 ± 64 (m) | –7.3 ± 7.2%, 29 ± 5% (m) | ND | 6.34 ± 1.79, 22.3 ± 6.1 (m) |
| 16d | 8770 ± 800, 2640 (m) | –15 ± 19%, 7.4 ± 4.2% (m) | ND | 6.12 ± 1.92, 12.4 ± 1.6 (m) |
| 17 | 38 ± 2% | >1000 | ND | 26.6 ± 7.6 |
| 19 | 1570 ± 390 | 15 ± 17% | ND | 18.9 ± 10.9, 120 (m) |
| 20 | 21 ± 2% | –0.5 ± 8.9% | ND | 80.7 ± 5.8 |
a
Radioligands used (concentration): [3H]8-cyclopentyl-1,3-dipropylxanthine ([3H]DPCPX, 21, A1, 0.5 nM), [3H]4-[2-[7-amino-2-(2-furyl)-1,2,4-triazolo[1,5-a][1,3,5]triazin-5-yl-amino]ethyl]phenol ([3H]ZM241385, 22, A2A, 1.0 nM) and [3H]21 (A2B, 5 nM), and [125I]N6-(4-Amino-3-iodobenzyl)adenosine-5′-N-methyluronamide ([125I]I-AB-MECA 3, A3, 0.1 nM), during 60 min incubations at 25 °C. N-Ethylcarboxamido-adenosine (NECA, 23, 100 μM) was used to define nonspecific binding.
b
ND, not determined.
c
Data from Gao et al.13