Table 2. Y1 receptor affinities (pKi) and antagonism (pKb) of the synthesized Nω-carbamoylated argininamides, determined by equilibrium competition binding with [3H]2 and in the Fura-2 Ca2+ assay, respectively.
| ||||
| Compd. | n | R | pKi ± SEM a | pIC50 ± SEM/pKb ± SEM b |
| 53 | 1 |
|
10.23 ± 0.06 | n.d. |
| 54 | 2 |
|
10.20 ± 0.05 | n.d. |
| 55 | 2 |
|
10.13 ± 0.04 | n.d. |
| 56 | 1 |
|
10.50 ± 0.04 | 10.26 ± 0.04/— |
| 57 | 1 |
|
10.17 ± 0.07 | 9.96 ± 0.12/— |
| 58 | 1 |
|
10.15 ± 0.06 | 9.90 ± 0.05/— |
| 59 | 1 |
|
10.28 ± 0.04 | 10.10 ± 0.04/— |
| 60 | 1 |
|
9.90 ± 0.07 | 10.21 ± 0.01/11.08 ± 0.01 |
| 61 | 1 |
|
9.62 ± 0.03 | 9.55 ± 0.03/10.43 ± 0.03 |
| 62 | 1 |
|
9.84 ± 0.05 | 10.04 ± 0.10/10.92 ± 0.10 |
| 63 | 1 |
|
9.95 ± 0.07 | 9.73 ± 0.05/10.61 ± 0.05 |
| 64 | 1 |
|
9.42 ± 0.05 | 9.23 ± 0.08/— |
| 65 | 1 |
|
9.16 ± 0.10 | 9.39 ± 0.10/10.27 ± 0.10 |
| 66 | 1 |
|
9.51 ± 0.09 | 10.18 ± 0.12/11.06 ± 0.12 |
| 67 | 1 |
|
7.34 ± 0.11 | 7.84 ± 0.08/8.71 ± 0.08 |
| 68 | 1 |
|
8.93 ± 0.12 | 9.62 ± 0.10/10.50 ± 0.10 |
| 69 | 1 |
|
8.96 ± 0.05 | 9.62 ± 0.09/10.49 ± 0.09 |
| 70 | 1 |
|
7.28 ± 0.07 | 8.12 ± 0.15/9.00 ± 0.15 |
| 71 | 1 |
|
6.42 ± 0.07 | 7.51 ± 0.01/8.39 ± 0.01 |
| 72 | 1 |
|
5.67 ± 0.05 | 6.34 ± 0.18/7.22 ± 0.18 |
| 73 | 1 |
|
7.25 ± 0.11 | 7.94 ± 0.03/8.82 ± 0.03 |
| 74 | 1 |
|
6.53 ± 0.07 | 7.79 ± 0.02/8.67 ± 0.02 |
| 75 | 1 |
|
6.52 ± 0.06 | 7.02 ± 0.04/7.90 ± 0.04 |
| 76 | 1 |
|
6.53 ± 0.01 | 6.28 ± 0.20/7.16 ± 0.20 |
| 78 | 1 | n.a. | 6.99 ± 0.04 | n.d. |
aRadioligand competition binding assay with [3H]2 (c = 0.15 nM, Kd = 0.044 nM7) at intact SK-N-MC cells. Mean values ± SEM from at least three independent experiments performed in triplicate.
bAntagonistic activities determined in a Fura-2 Ca2+ assay at intact HEL cells.13,14 Intracellular Ca2+ mobilization was induced by 10 nM pNPY after preincubation of the cells with the antagonist for 15 minutes.7 pKb values are not given, if the slope factor of the inhibition curve (four parameter logistic fit) was significantly different from (P ≤ 0.05, see Table S1†) and not close (≤1.25 or ≥0.75) to unity, as a steep slope factor might be indicative of a more complex interaction not purely following the law of mass action. Mean values ± SEM from at least three independent experiments performed in singlet. n.d.: not determined. n.a.: not applicable.