SAR of 3-pyrazole and amide replacements.
| Cmpd | Structure | GIRK1/2 (nM ± SEM; % ± SEM)a,b | GIRK1/4 (nM ± SEM; % ± SEM)a,b |
|---|---|---|---|
| 12a |
|
Inactive | Inactive |
| 12b |
|
>6000; >50 | >8000; >52 |
| 12c |
|
609 ± 169; 20 ± 1 | Inactive |
| 12d |
|
782 ± 155; 44 ± 3% | Inactive |
| 12e |
|
Inactive | Inactive |
| 12f |
|
>4000; >46 | Inactive |
| 12g |
|
723 ± 88; 103 ± 4 | 2869 ± 282; 99 ± 6 |
| 12h |
|
Inactive | Inactive |
a
Mean potency values (±SEM) were obtained from a minimum of triplicate determinations; values are average of n = 3.
b
Mean efficacy values (±SEM) shown are obtained from a minimum of triplicate determinations; values are normalized to standard compound, VU0466551.