Table 1.
Pharmacological Profiles of Di-halogenated Compounds at 5-HT2 Receptors.a
| Structure (HCl salt) | Compound | EC50, nM (Emax) | ||
|---|---|---|---|---|
| 5-HT2C | 5-HT2B | 5-HT2A | ||
| - | 5-HT | 0.18 (100%) | 1.0 (100%) | 1.9 (100%) |
| - | lorcaserin | 2.7 (98%) | 328 (80%) | 258 (67%) |
 |
(–)-20a | 30 (104%) | 400 (59%) | 511 (76%) |
| (+)-20a | 3.4 (108%) | 27 (69%) | 81 (81%) | |
 |
(–)-21a | 772 (73%) | NA | NA |
| (+)-21a | 7.3 (95%) | 453 (32%) | 361 (51%) | |
 |
(–)-22a | 116 (94%) | NA | 831 (17%) |
| (+)-22a | 8.7 (97%) | 1745 (35%) | 491 (21%) | |
 |
(–)-20b | 16 (108%) | 462 (62%) | 461 (72%) |
| (+)-20b | 9.5 (108%) | 209 (64%) | 437 (79%) | |
 |
(–)-21b | 509 (78%) | 9871 (29%) | NA |
| (+)-21b | 25 (95%) | 2182 (36%) | 2332 (30%) | |
 |
(–)-22b | 151 (89%) | 4464 (26%) | NA |
| (+)-22b | 36 (100%) | 3339 (35%) | NA | |
 |
(–)-20c | 16 (99%) | 329 (44%) | 235 (88%) |
| (+)-20c | 7.6 (97%) | 25 (59%) | 81 (93%) | |
 |
(–)-21c | 776 (70%) | 2521 (26%) | NA |
| (+)-21c | 24 (87%) | 506 (39%) | 654 (41%) | |
 |
(–)-22c | 308 (77%) | 1957 (22%) | NA |
| (+)-22c | 42 (87%) | 1001 (44%) | NA | |
 |
(–)-20d | 3.8 (93%) | 165 (64%) | 68 (86%) |
| (+)-20d | 13 (92%) | 354 (52%) | 212 (85%) | |
 |
(–)-21d | 386 (80%) | NA | NA |
| (+)-21d | 71 (86%) | NA | 934 (40%) | |
 |
(–)-22d | 165 (87%) | NA | 1081 (16%) |
| (+)-22d | 116 (90%) | 6983 (69%) | NA | |
|
(–)-20e | 14 (89%) | 696 (16%) | 84 (75%) |
| (+)-20e | 9.7 (95%) | 31 (45%) | 21 (85%) | |
 |
(–)-21e | 435 (75%) | NA | NA |
| (+)-21e | 18 (87%) | >10000 (26%) | 92 (58%) | |
 |
(–)-22e | 278 (84%) | NA | NA |
| (+)-22e | 61 (88%) | 714 (26%) | 167 (37%) | |
 |
(–)-20f | 0.95 (104%) | 51 (62%) | 38 (88%) |
| (+)-20f | 21 (98%) | 534 (46%) | 203 (76%) | |
 |
(–)-21f | 224 (85%) | >10,000 (62%) | NA |
| (+)-21f | 232 (90%) | 5523 (99%) | 949 (22%) | |
 |
(–)-22f | 108 (93%) | 3962 (99%) | 426 (32%) |
| (+)-22f | 165 (70%) | NA | NA | |
 |
(–)-20g | 3.2 (96%) | 101 (91%) | 119 (72%) |
| (+)-20g | 24 (89%) | 2176 (60%) | 769 (77%) | |
 |
(–)-21g | 135 (80%) | 3486 (29%) | NA |
| (+)-21g | 49 (86%) | 961 (55%) | 798 (39%) | |
 |
(–)-22g | 104 (89%) | 5176 (57%) | NA |
| (+)-22g | 96 (92%) | 927 (55%) | NA | |
a
Data were acquired with recombinant, stably expressed human serotonin receptors in the HEK-293 cell line, using a fluorescence imaging plate reader (FLIPR) assay. “NA”, no activity (Emax < 15%) at 10 μM.