Table 1.
Binding affinities of N-H bivalent ligands 5a-f and 7a-f against [3H]-CP55,940 and [3H]-1
| Cmpd | n | Linker (atoms) | Displacement Assay vs. Tritiated Ligands: Ki (nM) in hCB1 (n=2) | Displacement vs. 3H-CP55,940: Ki (nM) in hCB2 | CB1/CB2 | |||
|---|---|---|---|---|---|---|---|---|
| 3H-CP55,940 | SEM | 3H-1 | SEM | |||||
| 1 | 6.18 | 1.2 | 1.18 | 0.1 | 313 | 50.6 | ||
| 5a | 2 | 5 | 229 | 75.0 | 94.0 | 8.00 | 1285 | 5.6 |
| 5b | 3 | 7 | 174 | 1.0 | 41.9 | 5.40 | 496 | 2.9 |
| 5c | 5 | 11 | 68.1 | 12.6 | 30.4 | 4.40 | 451 | 6.6 |
| 5d | 7 | 15 | 12.3 | 1.10 | 4.41 | 0.34 | 553 | 45.0 |
| 5e | 9 | 19 | 54.1 | 16.3 | 57.4 | 44.7 | a | >46 |
| 5f | 11 | 23 | 99.3 | 35.8 | 37.0 | 4.55 | a | >25 |
| 7a | 2 | 5 | 1225 | 359 | 506 | 56.5 | a | >2 |
| 7b | 3 | 7 | a | - | a | - | a | - |
| 7c | 5 | 11 | 349 | 36.5 | 230 | 4.50 | a | >7 |
| 7d | 7 | 15 | 46.7 | 1.85 | 19.5 | 1.35 | 622 | 13.3 |
| 7e | 9 | 19 | 14.0 | 2.10 | 5.44 | 0.62 | 419 | 29.9 |
| 7f | 11 | 23 | 4.56 | 0.83 | 2.30 | 0.20 | 305 | 66.9 |
a
Ki >highest standard of 2500 nM