Table 1.
compd | R | Ar | clogPb | D2R | D3R | D4R | D2/D3 | D4/D3 |
---|---|---|---|---|---|---|---|---|
Ki±S.E.M, nM | ||||||||
8a | 2-OCH3 | 3.9 | 390±42 | 20.5±4.3 | ND | 19 | - | |
8b | 2,3-diCl | 5.5 | 378±42 | 6.20±1.5 | 3090±650 | 61 | 498 | |
8c | 2-OCH3 | 3.7 | 329±36 | 28.6±6.0 | ND | 11 | - | |
8d | 2,3-diCl | 5.3 | 14600±5070 (9160±3730) | 6.10±0.8 (5.40±0.6) | 5340±2290 | 2400 (1700)c | 875 | |
8e | 2-OCH3 | 4.0 | 274±13 | 13.9±1.1 | ND | 20 | - | |
8f | 2,3-diCl | 4.9 | 279±63 | 8.00±1.4 | ND | 35 | - | |
8g | 2-OCH3 | 3.7 | 421±33 | 9.50±1.9 | 1490±39.6 | 44 | 157 | |
8h | 2,3-diCl | 5.4 | 526±51 | 4.00±0.9 | 3360±484 | 131 | 841 | |
8i | 2-OCH3 | 5.1 | 2890±1040 | 10.1±1.9 | 3180±922 | 286 | 315 | |
8j | 2,3-diCl | 6.1 | 4260±1990 | 2.60±0.7 | ND | 1640 | - | |
8k | 2-OCH3 | 3.7 | 241±38 | 3.80±0.8 | ND | 63 | - | |
8l | 2,3-diCl | 5.4 | 472±76 | 2.90±0.4 | ND | 163 | - | |
8m | 2-OCH3 | 3.3 | 302±32 | 4.60±0.4 | ND | 66 | - | |
8n | 2,3-diCl | 4.8 | 230±16 | 1.50±0.3 | ND | 153 | - | |
8o | 2,3-diCl | 5.3 | 195±25 | 6.10±0.9 | ND | 32 | - | |
1d | - | - | 5.3 | 93.3±12.0 | 0.7±0.1 | 375±18 | 133 | 540 |
(±)2e | - | - | 4.2 | 502±51.5 | 1.39±0.19 | 4900±1034 | 358 | 5300 |
Binding inhibition values determined using HEK 293 cells transfected with hD2LR or hD3R and125I-IABN radioligand as described.5,6
Partition coefficients (clogP) were calculated using ChemDraw Ultra, Version 11.0, CambridgeSoft 2007;
D2/D3 ratio using Ki values from chimera study in Table 4;
data previously reported in ref. 5;
data previously reported in ref. 11; ND = Not determined.