PMC full text:
J Med Chem. Author manuscript; available in PMC 2008 Dec 15.
Published in final edited form as:
J Med Chem. 2006 Feb 23; 49(4): 1420–1432.
doi: 10.1021/jm050797aTable 1
The affinity of 4 ([125I]RTI 55) and its inhibition of uptake of [3H]dopamine, [3H]serotonin, and [3H]norepinephrine by HEK-hDAT, HEK-hSERT and HEK-hNET cellsa
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|---|---|---|---|---|---|---|---|---|---|
| Cpd | R | DAT | DA | DRb | SERT | SER | NET | NE | |
| 4 | Ki (nM) | Uptake (IC50) | Ki (nM) | Uptake (IC50) | Ki (nM) | Uptake (IC50) | |||
| Cocaine | 432 ± 29 | 461 ± 46 | 1.06 | 358 ± 24 | 494 ± 51 | 2150 ± 190 | 378 ± 48 | ||
| a | O-2371 | 4-CH3 (R/S) | 21.4 ± 4.6 | 52.0 ± 20 | 2.43 | 3770 ± 560 | 2780 ± 590 | 195 ± 26 | 28.3 ± 8.1 |
| b | O-2442 | 4-CH3 (S) | 18.1 ± 3.0 | 16.3 ± 2.3 | 0.91 | 2220 ± 550 | 1070 ± 230 | 109 ± 45 | 11.3 ± 2.4 |
| c | O-2440 | 4-CH3 (R) | 1330 ± 300 | 1790 ± 320 | 1.35 | >10µM | >10µM | ||
| d | O-2387 | H | 33.7 ± 5.4 | 52.3 ± 6.2 | 1.55 | >10µM | 199 ± 45 | 56.0 ± 13 | |
| e | O-2370 | 4-F | 82.0 ± 25 | 185 ± 62 | 2.26 | >10µM | 830±140 | 171 ± 35 | |
| f | O-2419 | 4-Br | 51.0 ± 6.7 | 39.5 ± 7.5 | 0.77 | 830 ± 190 | 1050 ± 90 | 386 ± 53 | 83.0 ± 30 |
| g | O-2493 | 4-I | 81.4 ± 9.2 | 32.0 ± 11 | 0.39 | 301 ± 26 | 197 ± 35 | 310 ± 34 | 46.5 ± 8.4 |
| h | O-2495 | 3-I | 109 ± 32 | 52.0 ± 16 | 0.48 | 1400 ± 120 | 1070 ± 170 | 670 ± 130 | 81.0 ± 20 |
| i | O-2575 | 4-CN | 5900 ± 1100 | 1000 ± 170 | 0.17 | >10µM | >10µM | ||
| j | O-2577 | 4-CH2OH | 48.7 ± 2.2 | 44.3 ± 8.4 | 0.91 | >10µM | 150 ± 23 | 12.4 ± 2.8 | |
| k | O-2418 | 4-OH | 125 ± 23 | 49.7 ± 3.4 | 0.40 | >10µM | 1290 ± 480 | 86.7 ± 7.5 | |
| l | O-2443 | 4-NO2 | 266 ± 32 | 1110 ± 340 | 4.17 | 2460 ± 290 | 1110 ± 450 | 2690 ± 530 | 531 ± 67 |
| m | O-2417 | 4-OCH3 | 329 ± 33 | 283 ± 66 | 0.86 | 4080 ± 410 | 2430 ± 720 | 2600 ± 1000 | 235 ± 8.7 |
| n | O-2558 | 4-CO2CH3 | 360 ± 140 | 154 ± 50 | 0.43 | 3950 ± 690 | 2350 ± 560 | 1140 ± 320 | 22.8 ± 3.3 |
| o | O-2439 | 4-NHCOCH3 | 30.2 ± 2.0 | 67.9 ± 8.4 | 2.25 | >10µM | 4000 ± 1100 | 317 ± 64 | |
| p | O-2481 | 4-CF3 | >10µM | 959 ± 92 | 1030 ± 340 | >10µM | |||
| q | O-2537 | 4-C≡CCH3 | 61.0 ± 16 | 11.8 ± 2.8 | 0.19 | 6700 ± 1100 | 3300 ± 1100 | 69.8 ± 5.4 | 19.3 ± 4.1 |
| r | O-2479 | 2-CH3 | 59.7 ± 9.0 | 63.0 ± 19 | 1.06 | 3720 ± 520 | 2020 ± 670 | 425 ± 63 | 19.7 ± 3.3 |
| s | O-2480 | 3-CH3 | 51.0 ± 14 | 62.9 ± 6.9 | 1.23 | 5900 ± 1600 | 4400 ± 1100 | 216 ± 38 | 9.4 ± 0.8 |
| t | O-2482 | Naphthyl | 20.1 ± 7.1 | 40.0 ± 13 | 1.99 | 33.1 ± 1.1 | 46.0 ± 5.5 | 136 ± 27 | 11.7 ± 0.9 |
| u | O-2390 | 3,4-Cl2 | 11.5 ± 1.4 | 43.0 ± 20 | 3.91 | 199 ± 50 | 600 ± 63 | 37.8 ± 3.2 | 21.0 ± 0.6 |
| v | O-2574 | 3,4-(OH) 2 | 84.0 ± 12 | 42.0 ± 11 | 0.50 | >10µM | 219 ± 71 | 7.6 ± 2.9 | |
| w | O-2512 | 3,4-(OCH3)2 | >10µM | 7460 ± 770 | 1540 ± 220 | >10µM | |||
| x | O-2441 | 4-Furan | 105 ± 17 | 122 ± 18 | 1.16 | 3330 ± 1200 | 2180 ± 440 | 95 ± 20 | 93 ± 38 |
| y | O-2438 | 4-Thiophene | 460 ± 120 | 539 ± 69 | 1.17 | 3320 ± 280 | 1960 ± 720 | 370 ± 160 | 263 ± 94 |
| z | O-2446 | 4-Mepyrrole | 3850 ± 330 | 5400 ± 1600 | 1.40 | >10µM | >10µM | ||
aNumbers represent the means ± SEM from at least three independent experiments, each conducted with duplicate (for binding assays) or triplicate (for uptake assays) determinations. When the Ki or the IC50 for the test compound is greater than 10 µM, only two experiments were conducted and no standard error was reported. Data from Oregon Health & Science University and VA Medical Center, Portland, OR.
bDR = Discrimination Ratio