Table 1.
Binding affinities of 4-substituted 2-dimethylaminotetralins at 5HT2A, 5HT2B and 5HT2C and H1 receptors
| Analog number | R | trans. | Affinity (Ki ± SEM; nM)
|
Ratio of affinities | ||||
|---|---|---|---|---|---|---|---|---|
| 5-HT2A | 5-HT2B | 5-HT2C | H1 | 2A/2C | H1/2C | |||
| “PAT” | C6H5 | (+) | 470(46) | 240(41) | 430(86) | 30(4) | 1.09 | 0.07 |
| (−) | 100(10) | 94(25) | 30(3) | 2(1) | 3.33 | 0.07 | ||
| 5a | 3′-F-C6H4 | (+) | 320(26) | 110(28) | 200(30) | 94(15) | 1.60 | 0.47 |
| (−) | 110(26) | 70(5) | 43(14) | 3(0.3) | 2.56 | 0.07 | ||
| 5b | 3′-Cl-C6H4 | (+) | 130(8.7) | 50(7) | 170(43) | 80(20) | 0.76 | 0.47 |
| (−) | 40(5) | 30(2) | 8(3) | 10(2) | 5.00 | 1.25 | ||
| 5c | 3′-Br-C6H4 | (+) | 260(22) | 40(8) | 200(30) | 60(10) | 1.30 | 0.30 |
| (−) | 20(3) | 8(2) | 4(1) | 30(2) | 5.00 | 7.50 | ||
| 5d | 3′-CF3-C6H4 | (+) | 1300(67) | 200(50) | 230(20) | 4100(160) | 5.65 | 17.83 |
| (−) | 80(10) | 60(20) | 10(2) | 230(27) | 8.00 | 23.00 | ||
| 5e | 3′-NO2-C6H4 | (+) | 500(20) | 20(6) | 120(13) | 1000(80) | 4.17 | 8.33 |
| (−) | 74(18) | 70(20) | 10(1) | 800(100) | 7.40 | 80.00 | ||
| 5f | 4′-F-C6H4 | (+) | 71(12) | 66(12) | 75(12) | 8(1) | 0.95 | 0.11 |
| (−) | 140(24) | 400(80) | 68(11) | 4(1) | 2.06 | 0.06 | ||
| 5g | 4′-Cl-C6H4 | (+) | 50(8) | 80(10) | 55(17) | 6(1) | 0.91 | 0.11 |
| (−) | 250(37) | 300(30) | 120(9.0) | 8(1) | 2.08 | 0.07 | ||
| 5h | 4′-Br-C6H4 | (+) | 60(10) | 30(9) | 70(8) | 530(62) | 0.86 | 7.57 |
| (−) | 220(29) | 210(15) | 100(3) | 1100(53) | 2.20 | 11.00 | ||
| 5i | 4′-CF3-C6H4 | (+) | 210(16) | 250(41) | 220(27) | 230(35) | 0.95 | 1.05 |
| (−) | 2000(200) | 540 (120) | 520(51) | 5100(360) | 3.85 | 9.81 | ||
| 5ja | 4′-NO2-C6H4 | racemic | 8100(180) | 4100 (510) | 1000 (100) | 680(31) | 8.10 | 0.68 |
| 5k | 2′-Br-C6H4 | (+) | 760(73) | 4100(510) | 78(16) | 2600(340) | 9.74 | 33.33 |
| (−) | 1100(130) | 650(72) | 70(8) | 4200(460) | 15.71 | 60.00 | ||
| 5l | cyclohexyl | (+) | 80(4) | 170(13) | 30(4) | 2(0.2) | 2.67 | 0.07 |
| (−) | 20(5) | 20(1) | 7(2) | 2(1) | 2.86 | 0.29 | ||
| 5m | cyclooctyl | (+) | 370(20) | 40(20) | 800(100) | >10000 | 0.46 | NA |
| (−) | 30(9) | 10(4) | 30(8) | 430(62) | 1.00 | 14.33 | ||
| 5n | 3′-Ph-C6H4 | (+) | 650(62) | 200(40) | 1000(10) | >10000 | 0.65 | NA |
| (−) | 44(17) | 73(13) | 5(2) | 200(20) | 8.80 | 40.00 | ||
| 5ob | 2′-Cl-C6H4 | (+) | 2800(110) | 710(64) | 50(10) | 60(20) | 56.00 | 1.20 |
| (−) | 2400(280) | 300(30) | 290(47) | 190(25) | 8.28 | 0.66 | ||
| 5pb | 2′-Me-C6H4 | (+) | 700(90) | 6000 (1000) | 2000 (200) | 120(5.1) | 0.35 | 0.06 |
| (−) | 1000(200) | 800 (100) | 1600 (150) | 400(40) | 0.63 | 0.25 | ||
NA – Not applicable.
a
Racemic mixture could not be resolved using chiral HPLC system;
b
Racemic mixture prepared by published procedure21 and resolved using chiral HPLC system.