Table 4. Structure and Adenosine Receptor Affinities of Series III: Alkyl 8-Halo-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylates (Cmpds 16a–x).
| |
Ki (nM) or % at 1 μM |
||||||
|---|---|---|---|---|---|---|---|
| compound | R4 | R3 | X | hA1a | hA2Ab | hA2Bc | hA3d |
| 16a | 2-furyl | Et | F | 10% | 29% | 6.60 ± 1.0 | 2% |
| 16b (ISAM-163) | 2-furyl | i-Pr | F | 11% | 2% | 3.05 ± 0.7 | 3% |
| 16c | 3-furyl | Et | F | 29% | 21% | 13.7 ± 0.9 | 2% |
| 16d | 3-furyl | i-Pr | F | 14% | 31% | 8.60 ± 0.5 | 4% |
| 16e | 2-thienyl | Et | F | 1% | 3% | 724 ± 8 | 3% |
| 16f | 2-thienyl | i-Pr | F | 2% | 1% | 668 ± 6 | 7% |
| 16g | 3-thienyl | Et | F | 1% | 1% | 187 ± 2 | 3% |
| 16h | 3-thienyl | i-Pr | F | 2% | 1% | 75.5 ± 3.2 | 5% |
| 16i | 2-furyl | Et | Cl | 23% | 10% | 8.42 ± 1.4 | 4% |
| 16j (ISAM-161) | 2-furyl | i-Pr | Cl | 35% | 24% | 5.03 ± 0.3 | 2% |
| 16k | 3-furyl | Et | Cl | 31% | 43% | 7.21 ± 0.4 | 4% |
| 16l (ISAM-M89A) | 3-furyl | i-Pr | Cl | 27% | 176 ± 4 | 6.10 ± 0.7 | 1% |
| 16m | 2-thienyl | Et | Cl | 3% | 2% | 41% | 1% |
| 16n | 2-thienyl | i-Pr | Cl | 2% | 2% | 837 ± 11 | 1% |
| 16o | 3-thienyl | Et | Cl | 2% | 7% | 911 ± 14 | 8% |
| 16p | 3-thienyl | i-Pr | Cl | 7% | 7% | 165 ± 9 | 4% |
| 16q | 2-furyl | Et | Br | 18% | 29% | 26.9 ± 0.8 | 33% |
| 16r (ISAM-157) | 2-furyl | i-Pr | Br | 25% | 2% | 5.23 ± 0.4 | 10% |
| 16s (ISAM-M114A) | 3-furyl | Et | Br | 1% | 37% | 3.32 ± 0.4 | 25% |
| 16t | 3-furyl | i-Pr | Br | 2% | 509 ± 6 | 8.20 ± 1.1 | 2% |
| 16u | 2-thienyl | Et | Br | 6% | 3% | 55% | 6% |
| 16v | 2-thienyl | i-Pr | Br | 1% | 1% | 115 ± 3 | 1% |
| 16w | 3-thienyl | Et | Br | 1% | 9% | 537 ± 8 | 1% |
| 16x | 3-thienyl | i-Pr | Br | 2% | 1% | 61.1 ± 1.8 | 4% |
| DPCPX | 2.20 ± 0.2 | 157 ± 3 | 73.2 ± 1.4 | 1722 ± 11 | |||
| ZM241385 | 683 ± 4 | 1.9 ± 0.1 | 65.7 ± 1.1 | 863 ± 4 | |||
| NECA | 14.0 ± 1 | 20.0 ± 3 | 2400 ± 35 | 6.20 ± 0.9 | |||
Displacement of specific [3H]DPCPX binding in human CHO cells expressed as Ki in nanomolars (n = 3) or percentage displacement of specific binding at a concentration of 1 μM (n = 2).
Displacement of specific [3H]4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol binding in human HeLa cells expressed as Ki in nanomolars (n = 3) or percentage displacement of specific binding at a concentration of 1 μM (n = 2).
Displacement of specific [3H]DPCPX binding in human HEK-293 cells expressed as Ki in nanomolars (n = 3) or percentage displacement of specific binding at a concentration of 1 μM (n = 2).
Displacement of specific [3H]NECA binding in human HeLa cells expressed as Ki in nanomolars (n = 3) or percentage displacement of specific binding at a concentration of 1 μM (n = 2).