Table 3.
Binding Affinity and Selectivity for Selected Analogues at the hM1-hM5mAcChRsa
| Compd |
Ki, nM
|
||||
|---|---|---|---|---|---|
| hM5 | hM1 (M1/M5)b | hM2(M2/M5)b | hM3(M3/M5)b | hM4 (M4/M5)b | |
| 1 | 17.6 | 7.5 (0.4) | 9.5 (0.5) | 6.5 (0.4) | 36.9 (2.1) |
| 8 | 420 | 170 (0.4) | 1,100 (2.6) | 1,370 (3.3) | 1,730 (4.1) |
| 20 | 470 | 3,290 (7.0) | 2,030 (4.3) | 4,070 (8.7) | 11,500 (24) |
| 28 | 230 | 1,390 (6.0) | >100,000 (>435) | 31,100 (135) | 10,500 (46) |
| 45 | 60 | 290 (4.8) | 1,170 (20) | 2,840 (47) | 1,890 (32) |
| 56 | 2,240 | 25,300 (11) | >100,000 (>45) | >100,000 (>45) | >100,000 (>45) |
| 57 | 5,040 | 24,400 (4.8) | >100,000 (>20) | >100,000 (>20) | >100,000 (>20) |
| 63 | 740 | 5,270 (7.1) | 540 (0.7) | 4,890 (6.6) | 5,740 (7.8) |
| 66 | 3,340 | 27,000 (8.0) | >100,000 (>30) | >100,000 (>30) | >100,000 (>30) |
a
At least three independent experiments with samples evaluated in duplicate were performed to obtain the Ki value;
b
Numbers in the parentheses are the ratios of binding affinity between M5 and the respective subtype.