Table 2. Structure and Adenosine Receptor Affinities of Series I: Alkyl 7,8-Dihalo-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylates (Cmpds 14a–x).
| |
Ki (nM) or % at 1 μM |
||||||
|---|---|---|---|---|---|---|---|
| compound | R4 | R3 | X | hA1a | hA2Ab | hA2Bc | hA3d |
| 14a | 2-furyl | Et | F | 1% | 2% | 44.1 ± 1.7 | 2% |
| 14b | 2-furyl | i-Pr | F | 13% | 22% | 11.9 ± 1.1 | 14% |
| 14c | 3-furyl | Et | F | 22% | 36% | 28.2 ± 0.8 | 17% |
| 14d | 3-furyl | i-Pr | F | 17% | 16% | 52.9 ± 1.5 | 20% |
| 14e | 2-thienyl | Et | F | 2% | 3% | 25% | 5% |
| 14f | 2-thienyl | i-Pr | F | 1% | 1% | 1% | 10% |
| 14g | 3-thienyl | Et | F | 1% | 1% | 519 ± 7 | 5% |
| 14h | 3-thienyl | i-Pr | F | 1% | 3% | 43% | 4% |
| 14i | 2-furyl | Et | Cl | 2% | 5% | 9% | 1% |
| 14j | 2-furyl | i-Pr | Cl | 43% | 12% | 117 ± 5 | 7% |
| 14k | 3-furyl | Et | Cl | 33% | 34% | 54.7 ± 3.2 | 6% |
| 14l | 3-furyl | i-Pr | Cl | 4% | 31% | 36% | 8% |
| 14m | 2-thienyl | Et | Cl | 2% | 1% | 9% | 11% |
| 14n | 2-thienyl | i-Pr | Cl | 1% | 4% | 1% | 9% |
| 14o | 3-thienyl | Et | Cl | 5% | 1% | 9% | 1% |
| 14p | 3-thienyl | i-Pr | Cl | 2% | 1% | 359 ± 4 | 6% |
| 14q | 2-furyl | Et | Br | 1% | 17% | 37% | 2% |
| 14r | 2-furyl | i-Pr | Br | 11% | 28% | 62.6 ± 1.9 | 21% |
| 14s | 3-furyl | Et | Br | 2% | 2% | 7% | 10% |
| 14t | 3-furyl | i-Pr | Br | 1% | 1% | 32% | 9% |
| 14u | 2-thienyl | Et | Br | 2% | 7% | 12% | 5% |
| 14v | 2-thienyl | i-Pr | Br | 1% | 1% | 9% | 3% |
| 14w | 3-thienyl | Et | Br | 2% | 7% | 47% | 4% |
| 14x | 3-thienyl | i-Pr | Br | 4% | 1% | 9% | 8% |
| 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).