From: Design, synthesis, and preliminary evaluation of a potential synthetic opioid rescue agent
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Cmpd | R1 | R2 | R3 | R4 | LogPa | CNS MPOa | MOR antagonism IC50 (nM)b,c (Imax)d | MOR agonism EC50 (nM)b (% efficacy)e | |
Fentanyl |  |  |  |  | 3.82 | 4.17 | NT | 0.22 ± 0.04 (103.35 ± 0.28) | |
Morphine |  |  |  |  | 0.90 | 4.94 | NT | 5.92 ± 0.95 (103.00 ± 0.56) | |
Oxycodone | CH3 | =O | OH | OH | 1.03 | 5.45 | NT | 102.12 ± 51.64 (105.78 ± 0.51) | |
Naloxone (4a) | Allyl | =O | OH | OH | 1.48 | 5.31 | 51.16 ± 13.42 (120.11 ± 4.02) | 3.15 ± 0.48 (22.36 ± 5.56) | |
Naltrexone (4b) | CPM | =O | OH | OH | 1.27 | 4.83 | 8.82 ± 1.53 (102.69 ± 0.94) | 2.14 ± 1.20 (29.61 ± 6.40) | |
β-FNA | CPM | NHCOCH=CHCO2Me, H | OH | OH | 1.08 | 3.13 | 31.02 ± 8.34 (59.98 ± 9.42) | NT | |
CCAM | CPM | =O | NHCOCH=CH(4-ClC6H4) | OH | 3.99 | 3.17 | 29.57 ± 2.98 (137.69 ± 5.98) |  > 10,000 | |
7 | CPM | =O | OH | OCH3 | 1.82 | 5.09 | > 10,000 | 103.02 ± 50.94 (45.87 ± 8.62) | |
8 | CPM | =O | OH | H | 1.97 | 5.03 | > 10,000 | 138.63 ± 55.18 (27.42 ± 5.41) | |
9 | CPM | =O | H | OH | 2.07 | 5.03 | 1.51 ± 0.68 (50.23 ± 4.32) | 0.27 ± 0.06 (71.33 ± 4.16) | |
10 | CPM | =O | OCOCH=CH(4-ClC6H4) | OH | 4.95 | 2.54 | > 10,000 | 386.90 ± 115.16 (68.74 ± 8.13) | |
11 | CPM | =O | OCOCH=CH(4-CH3C6H4) | OH | 4.85 | 2.74 | > 10,000 | 168.35 ± 31.99 (68.88 ± 11.09) | |
12 | CPM | =O | OCOCH=CHC6H5 | OH | 4.34 | 3.35 | > 10,000 | 6.60 ± 0.50 (89.14 ± 3.45) | |
13 | CPM | =O | OCOCH2CH2C6H5 | OH | 4.05 | 3.64 | > 10,000 | 16.68 ± 1.60 (78.98 ± 3.84) | |
14 | CPM | =O | OCOCH2CH3 | OH | 2.47 | 5.12 | 4.22 ± 1.13 (115.18 ± 2.54) | 4.98 ± 2.16 (19.63 ± 5.24) | |
15 | CPM | =O | OCH2CH2CH2Ph | OH | 4.34 | 3.44 | > 10,000 | 0.38 ± 0.11 (101.01 ± 1.86) | |
16 | CPM | =O | OCH2CH2CH2Cy | OH | 4.81 | 2.93 | > 10,000 | 1.89 ± 0.61 (98.55 ± 3.8) | |
17 | CPM | =O | OCH3 | OH | 1.89 | 5.12 | 13.26 ± 6.29 (71.74 ± 12.10) | 2.99 ± 1.56 (25.31 ± 2.76) | |
18 | CPM | =O | OCH2Ph | OH | 3.61 | 4.31 | 38.95 ± 15.76 (102.54 ± 26.42) | 15.38 ± 3.52 (19.98 ± 1.1) | |
19 | CPM | =O | OCH2CH3 | OH | 2.23 | 5.04 | 3.97 ± 1.65 (89.24 ± 5.87) | 0.44 ± 0.22 (49.66 ± 8.51) | |
20 | CPM | =O | OCH2CH2CH3 | OH | 2.76 | 4.95 | 2.55 ± 0.94 (94.95 ± 15.00) | 6.57 ± 3.03 (38.72 ± 8.31) | |
21 | CPM | =O | OCH2CH=CH2 | OH | 2.60 | 4.95 | 2.58 ± 0.75 (96.84 ± 5.49) | 0.72 ± 0.33 (37.41 ± 8.47) | |
22 | CPM | =O | (R)-OCH2CHOHCH2OH | OH | 0.60 | 3.79 | 6.49 ± 1.49 (149.78 ± 15.31) | > 10,000 | |
5 | CPM | =CH2 | OH | OH | 1.95 | 4.72 | 2.13 ± 0.20 (128.85 ± 7.09) | > 10,000 | |
23 | CPM | α-OH, H | OH | OH | 0.84 | 4.43 | 20.83 ± 9.92 (69.00 ± 9.72) | 2.22 ± 1.04 (49.31 ± 11.57) | |
24 | CPM | β-OH, H | OH | OH | 0.84 | 4.43 | 5.85 ± 2.03 (110.63 ± 6.30) | 0.94 ± 0.35 (26.88 ± 4.74) | |
25 | CPM | α-OCH3, H | OH | OH | 1.49 | 4.77 | 18.59 ± 5.87 (85.54 ± 5.14) | 1.86 ± 0.39 (58.16 ± 4.45) | |
26 | CPM | β-OCH3, H | OH | OH | 1.49 | 4.77 | 4.52 ± 1.62 (99.67 ± 7.40) | 0.88 ± 0.43 (39.02 ± 5.62) | |
27 | CPM | H2 | OH | OH | 1.86 | 4.71 | 8.83 ± 3.52 (121.83 ± 5.64) | 0.88 ± 0.43 (31.69 ± 3.69) | |
28 | CPM | =CH2 | OCH2CH=CH2 | OH | 3.80 | 4.71 | 2.03 ± 0.96 (100.42 ± 18.87) | 0.34 ± 0.15 (38.30 ± 7.02) | |
29 | CPM | =CH2 | OCH2CH2CH3 | OH | 3.95 | 4.55 | 2.06 ± 0.53 (86.70 ± 5.46) | 1.21 ± 0.44 (16.99 ± 3.50) | |
30 | CPM | =CH2 | (R)-OCH2CHOHCH2OH | OH | 1.75 | 4.78 | 3.58 ± 1.28 (115.90 ± 8.44) | > 10,000 |