Table 2.
Cannabinoid receptor binding and in vivo effects of 1-pentyl-3-phenylacetylindoles with chloro, bromo and fluoro substituents at various positions on the phenyl ring.
| Compound | * R | * R′ | Affinities (nM)a | In Vivo ED50s (μmol/kg)** | Avg. Potency | |||
|---|---|---|---|---|---|---|---|---|
| CB1 | CB2 | SA | %MPE | RT | ||||
| JWH-203 | 2-Chlorophenyl | H | 8 (0.9) | 7 (1) | 0.1 (0.09–0.2) | 0.3 (0.2–0.6) | 6 (5–6) | 2.1 |
| JWH-204 | 2-Chlorophenyl | CH3 | 13 (0.7) | 25 (1) | 0.8 (0.3–1.7) | 0.6 (0.6–0.8) | 2 (1.4–2.5) | 1.1 |
| JWH-237 | 3-Chlorophenyl | H | 38 (10) | 106 (2) | 1.5 (0.9–3) | 3 (3–6) | 3 (2.6–6) | 2.5 |
| JWH-303 | 3-Chlorophenyl | CH3 | 117 (10) | 138 (12) | 90% (85 μg/kg) | 100% (85 μg/kg) | −4 (85 μg/kg) | --- |
| JWH-206 | 4-Chlorophenyl | H | 389 (25) | 498 (37) | 76% (29 μg/kg) | inactive (29 μg/kg) | inactive (29 μg/kg) | --- |
| JWH-207 | 4-Chlorophenyl | CH3 | 1598 (134) | 3723 (110) | Inactive (28 μg/kg) | inactive (28 μg/kg) | inactive (28 μg/kg) | --- |
| JWH-249 | 2-Bromophenyl | H | 8 (2) | 20 (2) | 1 (0.5–2) | 0.3 (0.3–0.5) | 1 (0.8–1.3) | 0.8 |
| JWH-305 | 2-Bromophenyl | CH3 | 15 (2) | 29 (5) | 1.5 (0.2–7.5) | 1.8 (1.3–2.5) | 5 (5–8) | 2.8 |
| JWH-248 | 4-Bromophenyl | H | 1028 (39) | 657 (19) | Inactive (26 μg/kg) | inactive (26 μg/kg) | inactive (26 μg/kg) | --- |
| JWH-304 | 4-Bromophenyl | CH3 | 3363 (332) | 2679 (688) | NT | NT | NT | --- |
| JWH-311 | 2-Fluorophenyl | H | 23 (3) | 39 (3) | 2.5 (out of range) | 1.2 (0.9–1.9) | ~ 9 μg/kg | 4.2 |
| JWH-314 | 2-Fluorophenyl | CH3 | 39 (2) | 76 (4) | NT | NT | NT | --- |
| JWH-312 | 3-Fluorophenyl | H | 72 (7) | 91 (20) | 6 (5–7) | 1.9 (1.2–2.5) | 5.6 (5.3–5.9) | 4.5 |
| JWH-315 | 3-Fluorophenyl | CH3 | 430 (24) | 182 (23) | NT | NT | NT | --- |
| JWH-313 | 4-Fluorophenyl | H | 422 (19) | 365 (92) | Inactive (9 μg/kg) | inactive (9 μg/kg) | inactive (9 μg/kg) | --- |
| JWH-316 | 4-Fluorophenyl | CH3 | 2862 (670) | 781 (105) | NT | NT | NT | --- |