Table 1.
In vitro binding affinity values, molecular weight (MW) and lipophilicity (cLogD7.4) of CLZ, DCZ, 1 and fluorinated isosteres of 1. Binding affinity data are mean Ki ± SD (n = 3)
 | ||||||||
|---|---|---|---|---|---|---|---|---|
| Compound | R | F position | X | Ki, nM | Structural properties1 | |||
| hM3Dq | hM4Di | MW | cLogD7.4 | |||||
| CLZ2 | Me | - | Cl | 3.5 ± 1.3 | 2.8 ± 0.7 | 327 | 2.9 | |
| DCZ8 | Me | - | H | 6.3 | 4.2 | 292 | 2.5 | |
| 115 | Et | - | Cl | 4.3 ± 2.9 | 4.3 ± 0.1 | 341 | 3.4 | |
| 7a18 | Et | 1 | Cl | 1.7 ± 0.1 | 8.7 ± 2.1 | 359 | 3.1 | |
| 7b18 | Et | 2 | Cl | 10.5 ± 1.5 | 23.5 ± 4.5 | 359 | 2.9 | |
| 7c | Et | 3 | Cl | 51.4 ± 7.5 | 51 ± 9 | 359 | 3.0 | |
| 7d18 | Et | 4 | Cl | 1.9 ± 0.2 | 3.6 ± 0.8 | 359 | 3.1 | |
| 7e | Et | 1 | H | 4.8 ± 0.6 | 14.2 ± 3.3 | 324 | 2.3 | |
| 7f | Et | 2 | H | 33.5 ± 4.1 | 118 ± 23 | 324 | 2.1 | |
| 7g | Et | 3 | H | 101 ± 20 | 149 ± 28 | 324 | 2.2 | |
| 7h | Et | 2, 4 | Cl | 8.1 ± 0.9 | 18.1 ± 5.4 | 377 | 3.4 | |
| 7i | Et | - | F | 23.7 ± 2.5 | 12.9 ± 2.2 | 324 | 2.3 | |
1
Calculated using ACD/Percepta software