Table 6.
Adenosine receptor affinities of tricyclic xanthine derivatives
| Ki (nM)a | |||||
|---|---|---|---|---|---|
| A1 | A2A | A2B | A3 | ||
| Imidazo[2,1-i]purin-5-ones | |||||
| 127 | KF20274 | 2.7 (r)1 | 290 (r)1 | nd | nd |
| 128 | 22 (h)2 6 (r)2 |
4,400 (h)2 2,700 (r)2 |
580 (h)2 | >10,000 (h)2 | |
| 129 | PSB-10 | 1,700 (h)3 805 (r)4 |
2,700 (h)3 6,040 (r) 4 |
nd | 0.441 (h) 4 |
| 130 | PSB-11 | 1,640 (h)3 440 (r)3 |
1,280 (h)3 2,100 (r)3 |
2,100 (m)4 | 2.34 (h)3 KD 4.9 (h)5 |
| 131 | KF26777 | 1,800 (h)6 | 470 (h)6 | 620 (h)6 | 0.20 (h)6 |
| 132 | 14,900 (r)4 | 424 (r)4 | 3,700 (m)4 | 30,600 (h)4 | |
| Pyrimido[2,1-f]purinediones | |||||
| 133 | 15,000 (r)7 | 16,000 (r)7 | nd | nd | |
| 134 | 20,000 (r)7 | >250,000 (r)7 | nd | nd | |
| 135 | >25,000 (r)8 | 998 (r) 8 | 5,200 (h)8 | 12,300 (h)8 | |
| 136 | 26,800 (h)9 ≥25,000 (r)9 |
2,870 (h)9 219 (r)9 |
ca. 10,000 (h)9 | >10,000 (h)9 | |
| 137 | 16,700 (h)9 >25,000 (r)9 |
1,880 (h)9 147 (r)9 |
ca. 10,000 (h)9 | >10,000 (h)9 | |
| 138 | >25,000 (r)10 | 11,300 (h)10 699 (r)10 |
nd | nd | |
| 139 | 89 (r)10 | 478 (r)10 | nd | 1,290 (h)10 | |
| 140 | >10,000 (h)11 >25,000 (r)11 |
2,890 (h)11 320 (r)11 |
ca. 10,000 (h)11 | >10,000 (h)11 | |
| 141 | >25,000 (h)11 ca. 25,000 (r)11 |
630 (h)11 230 (r)11 |
7,200 (h)11 | >10,000 (h)11 | |
| 142 | >25,000 (h)11 ca. 25,000 (r)11 |
4,560 (h)11 330 (r)11 |
ca. 10,000 (h)11 | >10,000 (h)11 | |
| 143 | 620(r)11 | 860(r)11 | 590 (h)11 | 3,660 (h)11 | |
| Pyrido[2,1-f]purinediones | |||||
| 144 | 50 (h)12 | 119 (h)12 | nd | 4.0 (h)12 | |
| 145 | >10,000 (h)12 | >10,000 (h)12 | nd | 35 (h)12 | |
| 146 | >1,000 (h)13 | 242 (h)13 | nd | 4.2 (h)13 | |
| 147 | >1,000 (h)13 | >1,000 (h)13 | >1,000 (h)13 | 2.24 (h)13 | |
| Imidazo-, Pyrrolo- and Triazolopurinediones | |||||
| 148 | >1,000 (h)14 | >1,000 (h)14 | >1,000 (h)14 | 0.8 (h)14 | |
| 149 | >1,000 (h)14 | >1,000 (h)14 | >1,000 (h)14 | 3.5 (h)14 | |
| 150 | >10,000 (h)15 | 2,050 (h)15 | >100,000 (h)15 | 1,330 (h)15 | |
| 4,5-Dihydro-6H,8H-pyrimido[1,2,3-cd]purine-8,10-diones | |||||
| 151 | 1,440 (r)16 | 12,400 (r)16 | 42,600 (h)16 | nd | |
| 152 | PSB-63 | 16.9 (r)16 90.6 (h)16 |
22,000 (r)16 34,500 (h)16 |
3,190 (h)16 | >10,000 (h)16 |
| 153 | 40.6 (r)16 13.8 (h)16 |
23,400 (r)16 ca. 25,000 (h)16 |
22,300 (h)16 | 188 (h)16 | |
| Oxazolo[3,2-a]purinone | |||||
| 154 | 770 (r)17 | 20,600 (r)17 | nd | nd | |
a
h = human; m = mouse; r = rat; a few A2B data may be from functional (cAMP) studies; nd = no data available