TABLE 2.
In vitro binding affinity and efficacy data at hMOR for fentalogs with modifications at Region A or Regions A and B (2–22), Region B (23–29), and Region C (30–34)
| Compound # | Binding affinity |
Efficacy |
|
|---|---|---|---|
| Ki nM (SEM) | % stimulation (SEM) | EC50 nM (SEM) | |
| Fentanyl (1) | 1.6 (0.4) | 89 (9) | 32 (8) |
| 2 | 2.4 (0.4) | 75 (6) | 55 (10) |
| 3 | 7.2 (1.7) | 61 (4) | >1000 |
| 4 | 5(1) | 41 (5) | 160 (30) |
| 5 | 6.6 (0.7) | 56 (5) | 600 (190) |
| 6 | 1.3 (0.07) | 20.4 (2.9) | 9.3 (1.9) |
| 7 | 31 (6) | 36 (2) | 390 (96) |
| 8 | 64 (15) | 49 (6) | >2000 |
| 9 | 43 (10) | 43 (2) | >1000 |
| 10 | 19 (3) | 53 (7) | >500 |
| 11 | 2.1 (0.04) | 77.9 (1.4) | 68 (16) |
| 12 | 1.1 (0.5) | 81 (6) | 14(1) |
| 13 | 4.3 (0.9) | 82 (12) | 84 (11) |
| 14 | 6.6 (1.3) | 96 (11) | 137 (13) |
| 15 | 1.3 (0.02) | 102 (7) | 42 (13) |
| 16 | 4.5 (0.4) | 95 (12) | >500 |
| 17 | 24 (4) | 82 (16) | >1000 |
| 18 | 82 (17) | >65 | >2000 |
| 19 | 4.5 (0.7) | 64 (8) | 531 (136) |
| 20 | 3.5 (0.3) | 45 (10) | 80 (22) |
| 21 | 0.7 (0.06) | 50 (6) | 60 (15) |
| 22 | 17 (5) | 54(5) | >500 |
| 23 | 0.4 (0.1) | 87 (5) | 15 (4) |
| 24 | 10.0 (0.3) | 50(1) | 164 (24) |
| 25 | 4.2 (0.3) | 48 (10) | 79 (22) |
| 26 | 3.4 (0.3) | 69 (2) | 58 (10) |
| 27 | 5.5 (0.8) | 52 (7) | 450 (75) |
| 28 | 4.2 (0.7) | 31 (3) | >1000 |
| 29 | 45 (9) | 40 (3) | >1000 |
| 30 | 0.32 (0.06) | 100 (8) | 4.2 (0.6) |
| 31 | 1.1 (0.2) | 93 (4) | 25 (6) |
| 32 | 8(1) | 76 (5) | 350 (7) |
| 33 | 6.2 (0.7) | 83 (5) | 138 (21) |
| 34 | 14(1) | 86 (3) | >500 |
Note. All values are expressed as mean ± SEM of at least three separate assays performed in duplicate.