Table 1. Human 5-HT2 receptor subtype binding affinities (pKi ± SEM, and Ki in parentheses) and 5-HT2A/2C and (in parentheses) 5-HT2C/2A selectivities of serotonin, tryptamine, and the synthesized compounds.
| Compound | R5 | RX | RY | 5-HT2A pKi ± S.E.M. (Ki) |
5-HT2B pKi ± S.E.M. (Ki) |
5-HT2C pKi ± S.E.M. (Ki) |
Selectivity 5-HT2A/2C (5-HT2C/2A) |
|---|---|---|---|---|---|---|---|
| 5-HT | OH | 6.03 | N.D. | N.D. | N.D. | ||
| Tryptamine | H | 5.39 ± 0.25 (4073.80) |
6.96 ± 0.06 (109.65) |
7.02 ± 0.08 (95.50) |
0.021 (46.7) |
||
| 1 | H | H | H | 6.61 ± 0.11 (245.47) |
7.00 ± 0.06 (100) |
6.73 ± 0.06 (186.21) |
0.75 (1.33) |
| 2 | H | 2-OH | H | 6.94 ± 0.20 (114.82) |
7.17 ± 0.05 (67.61) |
7.07 ± 0.10 (85.11) |
0.73 (1.37) |
| 3 | H | 2-OMe | H | 7.05 ± 0.14 (89.13) |
7.33 ± 0.11 (46.77) |
6.65 ± 0.11 (223.87) |
2.56 (0.39) |
| 4 | H | 2-Me | H | 48 ± 1* | 6.47 ± 0.07 (338.84) |
6.18 ± 0.05 (660.69) |
N.D. |
| 5 | H | 2-Cl | H | 7.92 ± 0.12 (12.02) |
7.63 ± 0.04 (23.44) |
7.61 ± 0.03 (24.55) |
2.04 (0.49) |
| 6 | H | 2-Br | H | 6.71 ± 0.08 (194.98) |
7.13 ± 0.07 (74.13) |
6.47 ± 0.12 (338.84) |
1.74 (0.57) |
| 7 | H | 3-OH | H | 7.12 ± 0.07 (75.86) |
7.43 ± 0.07 (37.15) |
7.59 ± 0.06 (25.70) |
0.36 (2.8) |
| 8 | H | 3-Me | H | 7.84 ± 0.06 (14.45) |
7.77 ± 0.03 (16.98) |
7.13 ± 0.03 (74.13) |
5.10 (0.20) |
| 9 | H | 3-F | H | 6.59 ± 0.08 (257.04) |
6.90 ± 0.05 (125.89) |
6.67 ± 0.06 (213.80) |
0.84 (1.19) |
| 10 | H | 3-Cl | H | 7.35 ± 0.07 (44.67) |
7.46 ± 0.06 (34.67) |
7.01 ±0.08 (97.72) |
2.17 (0.46) |
| 11 | H | 3-Br | H | 8.09 ± 0.14 (8.13) |
7.66 ± 0.07 (21.88) |
7.12 ± 0.07 (75.86) |
8 (0.13) |
| 12 | H | 4-OH | H | 6.04 ± 0.12 (912.01) |
6.31 ± 0.08 (489.78) |
6.00 ± 0.08 (1000) |
1.09 (0.92) |
| 13 | H | 4-OMe | H | 6.34 ± 0.10 (457.09) |
7.16 ± 0.10 (69.18) |
6.45 ± 0.08 (354.81) |
0.78 (1.28) |
| 14 | H | 4-Me | H | 6.38 ± 0.08 (416.87) |
7.13 ± 0.04 (74.13) |
6.48 ± 0.04 (331.13) |
0.81 (1.23) |
| 15 | H | 4-OEt | H | 6.56 ± 0.09 (275.42) |
6.57 ± 0.06 (269.15) |
6.13 ± 0.11 (741.31) |
2.66 (0.36) |
| 16 | H | 4-Cl | H | 6.15 ± 0.10 (707.95) |
6.65 ± 0.14 (223.87) |
6.02 ± 0.08 (954.99) |
1.37 (0.73) |
| 17 | H | 4-Br | H | 6.00 ± 0.06 (1000) |
6.58 ± 0.09 (263.03) |
5.97 ± 0.08 (1071.52) |
1.09 (0.92) |
| 18 | H | 4-NO2 | H | 5.58 ± 0.07 (2630.27) |
6.70 ± 0.11 (199.53) |
5.85 ± 0.11 (1412.54) |
0.54 (1.85) |
| 19 | H | 2-OH | 3-OMe | 7.58 ± 0.06 (26.30) |
7.88 ± 0.06 (13.18) |
7.78 ± 0.06 (16.60) |
0.58 (1.72) |
| 20 | H | 2-OMe | 3-OMe | 5.82 ± 0.16 (1513.56) |
6.71 ± 0.03 (194.98) |
5.95 ± 0.07 (1122.02) |
0.73 (1.37) |
| 21 | H | 2-OH | 3-Br | 7.85 ± 0.05 (14.13) |
7.81 ± 0.07 (15.49) |
6.86 ± 0.08 (138.04) |
9.8 (0.10) |
| 22 | H | 2-OH | 3-F | 6.68 ± 0.05 (208.93) |
6.89 ± 0.04 (128.82) |
6.75 ± 0.07 (177.83) |
0.82 (1.22) |
| 23 | H | 2-OH | 5-Me | 6.13 ± 0.06 (741.31) |
6.81 ± 0.04 (154.88) |
6.57 ± 0.08 (269.15) |
0.36 (2.77) |
| 24 | H | 2-OH | 5-F | 6.12 ± 0.04 (758.58) |
7.11 ± 0.07 (77.62) |
6.98 ± 0.07 (104.71) |
0.14 (7.15) |
| 25 | H | 2-OMe | 5-F | 6.44 ± 0.08 (363.08) |
7.02 ± 0.07 (95.50) |
6.82 ± 0.14 (151.36) |
0.42 (2.40) |
| 26 | H | 2-OH | 5-Br | 6.51 ± 0.09 (309.03) |
N.D. | 6.14 ± 0.06 (724.44) |
2.39 (0.42) |
| 27 | H | 2-OMe | 5-Br | 5.95 ± 0.09 (1122.02) |
7.04 ± 0.05 (91.20) |
6.87 ± 0.09 (134.90) |
0.12 (8.22) |
| 28 | H | 2-OMe | 5-Cl | 6.01 ± 0.09 (977.24) |
6.10 ± 0.06 (794.33) |
5.88 ± 0.06 (1318.26) |
1.35 (0.74) |
| 29 | H | 2-OMe | 5-OMe | 6.48 ± 0.09 (331.13) |
7.24 ± 0.04 (57.54) |
7.06 ± 0.06 (87.10) |
0.26 (3.85) |
| 30 | H | 2-OH | 5-NO2 | 8 ± 4* | 6.05 (891.25) |
31 ± 4* | N.D. |
| 31 | H | 2-OH | 4-Br | 5.81 ± 0.10 (1548.82) |
6.96 ± 0.04 (109.65) |
6.22 ± 0.05 (602.56) |
0.38 (2.63) |
| 32 | H | 2-OMe | 4-OMe | 6.18 ± 0.09 (660.69) |
6.63 ± 0.04 (234.42) |
6.57 ± 0.09 (269.15) |
0.41 (2.44) |
| 33 | H | 2-OH | 6-Br | 5.78 ± 0.05 (1659.59) |
7.16 ± 0.02 (69.18) |
6.95 ± 0.09 (112.20) |
0.067 (15) |
| 34 | H | 2-OH | 6-F | 6.64 ± 0.06 (229.09) |
6.94 ± 0.04 (114.82) |
6.81 ± 0.08 (154.88) |
0.95 (1.05) |
| 35 | H | 2-OH | 3,5-diBr | 12 ± 4* | 5.22 (6025.60) |
26 ± 4* | N.D. |
| 36 | H | 3-OMe | 4-OMe | 5.89 ± 0.10 (1288.25) |
6.54 ± 0.07 (288.40) |
5.92 ± 0.11 (1202.26) |
0.92 (1.09) |
| 37 | OMe | H | H | 7.48 ± 0.07 (33.11) |
7.78 ± 0.11 (16.60) |
7.02 ± 0.05 (95.50) |
2.93 (0.34) |
| 38 | OMe | 2-OMe | H | 7.35 ± 0.05 (44.67) |
7.80 ± 0.06 (15.85) |
7.16 ± 0.07 (69.18) |
1.55 (0.65) |
| 39 | OMe | 2-Cl | H | 7.87 ± 0.06 (13.49) |
7.43 ± 0.09 (37.15) |
7.13 ± 0.08 (74.13) |
5.51 (0.18) |
| 40 | OMe | 2-Br | H | 7.91 ± 0.09 (12.30) |
7.54 ± 0.05 (28.84) |
7.15 ± 0.07 (70.79) |
5.66 (0.18) |
| 41 | OMe | 4-Br | H | 6.41 ± 0.04 (389.05) |
6.81 ± 0.07 (154.88) |
6.42 ± 0.04 (380.19) |
0.98 (1.02) |
| 42 | OMe | 2-OH | 5-OMe | 6.87 ± 0.04 (134.90) |
7.69 ± 0.05 (20.42) |
7.39 ± 0.07 (40.74) |
0.30 (3.31) |
| 43 | OMe | 2-OH | 5-F | 8.40 ± 0.16 (3.98) |
8.05 ± 0.07 (8.91) |
7.40 ± 0.09 (39.81) |
9.66 (0.10) |
*Binding inhibition at 10 μM