Table 3
Effects of side chain length and substitutions in the terminal carbon on receptor affinity and pharmacological potency
| No.3-a | Chemical Name | Structure | KD | ED50 | |
|---|---|---|---|---|---|
| SA | TF | RT | |||
| nM | mg/kg | ||||
| 29 | 3-(6-Carboxy-1,2-hexadienyl)-Δ8-THC | 3170 ± 105 | 24.3 | 23.9 | |
| O-1174 | 0 (10) | 53 (30) | –3.4 (30) | ||
| 30 | 3-(6-Amino-2-hexynyl)-Δ8-THC | 1300 ± 180 | |||
| O-1175 | 40 (30) | 40 (30) | –1.7 (30) | ||
| 31 | 3-(6-Isothiocyano-2-hexynyl)-Δ8-THC | 11.5 ± 2.3 | 10 | 4.3 | 24.2 |
| O-1176 | 65 (30) | 87 (30) | –3.0 (30) | ||
| 32 | 3-(2,7-Octadiynyl)-Δ8-THC | 4.7 ± 0.4 | 2.92 | 1.06 | |
| O-965 | 77 (3) | 74 (30) | –4.6 (30) | ||
| 33 | 3-(6-Cyano-2-hexynyl)-Δ8-THC | 0.77 ± 0.05 | |||
| O-823 | 43 (30) | 45 (30) | –2.3 (30) | ||
| 34 | cis-3-(6-Cyano-2-hexenyl)-Δ8-THC | 1.25 ± 0.51 | 0.17 | 0.08 | 0.15 |
| O-1237 | 91 (1) | 100 (1) | –5.0 (1) | ||
| 35 | 3-(6-Azido-2-hexynyl)-Δ8-THC | 2.14 ± 0.44 | 9.8 | 1.8 | 0.17 |
| O-1184 | 64 (10) | 84 (30) | –3.3 (30) | ||
| 36 | cis-3-(6-Azido-2-hexenyl)-Δ8-THC | 3.32 ± 0.59 | 0.02 | 0.08 | 0.16 |
| O-1238 | 75 (1) | 100 (1) | –6.1 (1) | ||
| 37 | 3-(6-Bromo-2-hexynyl)-Δ8-THC | 1.2 ± 0.1 | 4.78 | 29 | |
| O-806 | 0 (30) | 60 (30) | –3.8 (30) | ||
| 38 | cis-3-(6-Bromo-2-hexenyl)-Δ8-THC | 1.66 ± 0.66 | 0.16 | 0.13 | 0.05 |
| O-1236 | 86 (1) | 100 (1) | –5.7 (1) | ||
| 39 | cis-3-(6-Fluoro-2-hexenyl)-Δ8-THC | 20.9 ± 1.91 | 0.48 | 0.26 | 0.42 |
| O-1310 | 80 (1) | 100 (1) | –5.2 (1) | ||
| 40 | cis-3-(6-Hydroxy-2-hexenyl)-Δ8-THC | 53.7 ± 6.5 | 0.8 | 2.1 | 4.2 |
| O-1311 | 80 (10) | 74 (10) | –3.5 (10) | ||
| 41 | cis-3-(6-Methoxy-2-hexenyl)-Δ8-THC | 11.5 ± 0.16 | 0.16 | 0.16 | 0.41 |
| O-1312 | 74 (1) | 92 (1) | –4.2 (1) | ||
| 42 | cis-3-(6-Acetamido-2-hexenyl)-Δ8-THC | 16.7 ± 1.51 | 0.67 | 0.84 | 10.5 |
| O-1309 | 82 (3) | 90 (3) | –3.1 (3) | ||
| 43 | cis-3-(7-Nitro-2-heptenyl)-Δ8-THC | 3.56 ± 2.18 | 0.05 | 0.09 | 0.10 |
| O-1313 | 83 (1) | 92 (1) | –3.4 (1) | ||
Spontaneous activity (SA), tail-flick response (TF), and rectal temperature (RT) are expressed as ED50 values (mg/kg). A blank space indicates that calculation of an ED50 was not possible. The maximal effect with the dose in parentheses is given under the ED50 value. The KD values represent means ± S.E. of at least three separate experiments.
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↵3-a Listed below the boldface analog number is the reference number assigned by either Organix, Inc. (O) or Dr. Huffman (J.W.H.).