Table 2. Human 5-HT2 receptor subtype Ca2+ mobilization potencies (pEC50 ± SEM, and EC50 in parentheses) and relative efficacies (% of response to 5-HT), and 5-HT2A/2C and (in parentheses) 5-HT2C/2A selectivities of serotonin, tryptamine, and the synthesized compounds.
| Compound | R5 | RX | RY | 5-HT2A | 5-HT2C | Selectivity | ||
|---|---|---|---|---|---|---|---|---|
| pEC50 | % Emax | pEC50 | % Emax | 5-HT2A/2C (5-HT2C/2A) |
||||
| 5-HT | OH | — | — | 8.09 ± 0.06 (8.13) |
99.72 ± 1.93 | 9.87 ± 0.07 (0.13) |
98.29 ± 2.03 | 0.016 (62.5) |
| Tryptamine | H | — | — | 7.76 ± 0.07 (17.38) |
97.60 ± 2.34 | 8.93 ± 0.13 (1.17) |
107.8 ± 3.43 | 0.067 (14.9) |
| 1 | H | H | H | 6.79 ± 0.24 (162.18) |
61.65 ± 5.17 | 7.30 ± 0.15 (50.12) |
121.4 ± 6.58 | 0.31 (3.24) |
| 2 | H | 2-OH | H | 6.70 ± 0.11 (199.53) |
94.13 ± 4.59 | 7.47 ± 0.12 (33.88) |
85.85 ± 2.83 | 0.17 (5.89) |
| 3 | H | 2-OMe | H | 5.81 ± 0.07 (1548.82) |
62.98 ± 1.95 | 7.45 ± 0.10 (35.48) |
94.24 ± 3.75 | 0.023 (43.7) |
| 4 | H | 2-Me | H | 5.7 ± 0.15 (1995.26) |
44.44 ± 2.79 | 6.86 ± 0.09 (138.04) |
106.9 ± 2.90 | 0.069 (14.5) |
| 5 | H | 2-Cl | H | 6.33 ± 0.10 (467.74) |
25.52 ± 1.16 | 6.71 ± 0.14 (194.98) |
87.07 ± 4.96 | 0.42 (2.40) |
| 6 | H | 2-Br | H | 5.65 ± 0.27 (2238.72) |
29.33 ± 5.93 | 6.63 ± 0.13 (234.42) |
108.6 ± 5.20 | 0.10 (9.55) |
| 7 | H | 3-OH | H | 7.25 ± 0.23 (56.23) |
52.75 ± 4.63 | 8.17 ± 0.20 (6.76) |
96.34 ± 4.02 | 0.12 (8.32) |
| 8 | H | 3-Me | H | 7.21 ± 0.18 (61.66) |
32.98 ± 2.11 | 7.53 ± 0.06 (29.51) |
82.61 ± 2.11 | 0.48 (2.09) |
| 9 | H | 3-F | H | 6.41 ± 0.26 (389.05) |
33.82 ± 4.01 | 6.95 ± 0.10 (112.20) |
112.1 ± 4.84 | 0.29 (3.47) |
| 10 | H | 3-Cl | H | 6.92 ± 0.2 (120.23) |
57.91 ± 4.15 | 6.55 ± 0.11 (281.84) |
117.3 ± 4.82 | 2.34 (0.43) |
| 11 | H | 3-Br | H | 7.23 ± 0.14 (58.88) |
32.59 ± 1.64 | 7.26 ± 0.07 (54.95) |
106.7 ± 2.78 | 0.93 (1.07) |
| 12 | H | 4-OH | H | N.D. | N.D. | 6.84 ± 0.10 (144.54) |
99.65 ± 2.81 | N.D. |
| 13 | H | 4-OMe | H | 7.34 ± 0.06 (45.71) |
108.2 ± 2.78 | 8.08 ± 0.06 (8.32) |
91.44 ± 2.03 | 0.18 (5.49) |
| 14 | H | 4-Me | H | N.D. | N.D. | 5.92 ± 0.14 (1202.26) |
100.5 ± 5.36 | N.D. |
| 15 | H | 4-OEt | H | 6.44 ± 0.34 (363.08) |
36.73 ± 6.13 | 7.93 ± 0.17 (11.75) |
93.15 ± 3.26 | 0.032 (30.9) |
| 16 | H | 4-Cl | H | 7.23 ± 0.15 (58.88) |
79.96 ± 4.54 | 7.30 ± 0.11 (50.12) |
98.34 ± 4.18 | 0.85 (1.17) |
| 17 | H | 4-Br | H | N.D. | N.D. | 5.17 ± 0.08 (6760.83) |
110.2 ± 4.30 | N.D. |
| 18 | H | 4-NO2 | H | N.D. | N.D. | 6.28 ± 0.19 (524.81) |
92.05 ± 8.69 | N.D. |
| 19 | H | 2-OH | 3-OMe | 7.31 ± 0.34 (48.98) |
26.16 ± 2.34 | 7.03 ± 0.15 (93.33) |
107.4 ± 6.91 | 1.91 (0.52) |
| 20 | H | 2-OMe | 3-OMe | N.D. | N.D. | 5.44 ± 0.26 (3630.78) |
117.3 ± 9.18 | N.D. |
| 21 | H | 2-OH | 3-Br | 4.80 ± 0.24 (15848.93) |
40.38 ± 6.23 | 7.56 ± 0.10 (27.54) |
98.83 ± 2.83 | 0.0017 (575) |
| 22 | H | 2-OH | 3-F | 6.79 ± 0.18 (162.18) |
53.62 ± 4.49 | 7.77 ± 0.15 (16.98) |
103.5 ± 4.96 | 0.105 (9.55) |
| 23 | H | 2-OH | 5-Me | 6.96 ± 0.06 (109.65) |
43.57 ± 0.90 | 7.00 ± 0.08 (100) |
89.38 ± 3.86 | 0.91 (1.10) |
| 24 | H | 2-OH | 5-F | 7.12 ± 0.09 (75.86) |
71.64 ± 1.95 | 7.58 ± 0.12 (26.30) |
105.2 ± 2.19 | 0.35 (2.88) |
| 25 | H | 2-OMe | 5-F | 7.22 ± 0.09 (60.26) |
57.98 ± 1.95 | 7.28 ± 0.12 (52.48) |
109.7 ± 2.19 | 0.87 (1.15) |
| 26 | H | 2-OH | 5-Br | N.D. | N.D. | 6.15 ± 0.08 (707.95) |
107.8 ± 2.88 | N.D. |
| 27 | H | 2-OMe | 5-Br | 4.75 ± 0.08 (17782.79) |
69.04 ± 3.51 | 6.58 ± 0.14 (263.03) |
110.8 ± 4.63 | 0.015 (67.6) |
| 28 | H | 2-OMe | 5-Cl | 5.05 ± 0.07 (8912.51) |
69.21 ± 2.67 | 6.62 ± 0.10 (239.88) |
109.7 ± 3.35 | 0.027 (37.2) |
| 29 | H | 2-OMe | 5-OMe | 5.46 ± 0.04 (3467.37) |
38.97 ± 0.67 | 6.88 ± 0.09 (131.83) |
118.4 ± 4.45 | 0.038 (26.3) |
| 31 | H | 2-OH | 4-Br | 4.61 ± 0.21 (24547.09) |
62.53 ± 10.79 | 6.09 ± 0.09 (812.83) |
74.75± 2.60 | 0.033 (30.2) |
| 32 | H | 2-OMe | 4-OMe | N.D. | N.D. | 6.62 ± 0.13 (239.88) |
117.2 ± 4.59 | N.D. |
| 33 | H | 2-OH | 6-Br | 5.23 ± 0.67 (5888.44) |
34.40 ± 1.37 | 6.10 ± 0.08 (794.33) |
103.5 ± 2.91 | 0.13 (7.41) |
| 34 | H | 2-OH | 6-F | 7.40 ± 0.16 (39.81) |
49.28 ± 3.23 | 7.73 ± 0.19 (18.62) |
91.67 ±6.60 | 0.47 (2.13) |
| 36 | H | 3-OMe | 4-OMe | 5.65 ± 0.35 (2238.7) |
50.52 ± 8.27 | 7.24 ± 0.11 (57.54) |
100.5 ± 2.85 | 0.026 (38.9) |
| 37 | OMe | H | H | 7.69 ± 0.10 (20.42) |
63.19 ± 1.44 | 7.84 ± 0.13 (14.45) |
112.7 ± 3.47 | 0.71 (1.41) |
| 38 | OMe | 2-OMe | H | 8.70 ± 0.20 (1.99) |
83.66 ± 3.42 | 8.42 ± 0.16 (3.80) |
88.69 ± 4.22 | 1.91 (0.53) |
| 39 | OMe | 2-Cl | H | 7.92± 0.11 (12.02) |
47.74 ± 1.57 | 7.09 ± 0.09 (81.28) |
106.2 ± 4.32 | 6.76 (0.15) |
| 40 | OMe | 2-Br | H | 7.53 ± 0.06 (29.51) |
44.79 ± 0.99 | 7.56 ± 0.14 (27.54) |
105.1± 4.32 | 0.93 (1.07) |
| 41 | OMe | 4-Br | H | 5.73 ± 0.10 (1862.09) |
60.53 ± 2.41 | 6.88 ± 0.15 (131.83) |
93.52 ± 3.05 | 0.071 (14.1) |
| 42 | OMe | 2-OH | 5-OMe | 6.96 ± 0.06 (109.65) |
43.57 ± 0.90 | 7.00 ± 0.08 (100) |
89.38 ± 3.86 | 0.91 (1.1) |
| 43 | OMe | 2-OH | 5-F | 8.86 ± 0.10 (1.38) |
83.26 ± 2.26 | 8.44 ± 0.12 (3.63) |
106.1 ± 3.05 | 2.63 (0.38) |