Table 3. Structure and Adenosine Receptor Affinities of Series II: Alkyl 7-Halo-1,4-dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-3-carboxylates (Cmpds 15a–x).
| |
Ki (nM) or % at 1 μM |
||||||
|---|---|---|---|---|---|---|---|
| compound | R4 | R3 | X | hA1a | hA2Ab | hA2Bc | hA3d |
| 15a | 2-furyl | Et | F | 16% | 2% | 67.5 ± 3.1 | 10% |
| 15b | 2-furyl | i-Pr | F | 32% | 3% | 12.2 ± 1.2 | 5% |
| 15c | 3-furyl | Et | F | 26% | 21% | 25.0 ± 1.5 | 5% |
| 15d | 3-furyl | i-Pr | F | 25% | 11% | 136 ± 7 | 6% |
| 15e | 2-thienyl | Et | F | 25% | 1% | 37% | 11% |
| 15f | 2-thienyl | i-Pr | F | 11% | 2% | 23% | 6% |
| 15g | 3-thienyl | Et | F | 7% | 1% | 1031 ± 95 | 3% |
| 15h | 3-thienyl | i-Pr | F | 1% | 1% | 764 ± 11 | 1% |
| 15i | 2-furyl | Et | Cl | 26% | 2% | 18% | 4% |
| 15j | 2-furyl | i-Pr | Cl | 667 ± 12 | 17% | 44.3 ± 1.4 | 5% |
| 15k | 3-furyl | Et | Cl | 22% | 30% | 47.3 ± 1.9 | 3% |
| 15l | 3-furyl | i-Pr | Cl | 6% | 4% | 50% | 3% |
| 15m | 2-thienyl | Et | Cl | 2% | 3% | 1% | 1% |
| 15n | 2-thienyl | i-Pr | Cl | 1% | 3% | 7% | 1% |
| 15o | 3-thienyl | Et | Cl | 4% | 2% | 50% | 3% |
| 15p | 3-thienyl | i-Pr | Cl | 7% | 9% | 48% | 3% |
| 15q | 2-furyl | Et | Br | 22% | 21% | 48% | 5% |
| 15r | 2-furyl | i-Pr | Br | 46% | 1% | 273 ± 4 | 6% |
| 15s | 3-furyl | Et | Br | 10% | 1% | 318 ± 6 | 19% |
| 15t | 3-furyl | i-Pr | Br | 11% | 3% | 26% | 12% |
| 15u | 2-thienyl | Et | Br | 1% | 5% | 1% | 4% |
| 15v | 2-thienyl | i-Pr | Br | 1% | 6% | 11% | 8% |
| 15w | 3-thienyl | Et | Br | 4% | 3% | 43% | 3% |
| 15x | 3-thienyl | i-Pr | Br | 1% | 1% | 10% | 1% |
| 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 nM (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).