Table 1.
Binding data (pKi values) of compounds DPH, 1–4, 115–136 and 141–145 determined at human HxRs (x=1–4).[a]
|
compound |
hH1R[b] |
hH2R[c] |
hH3R[d] |
hH4R[e] |
||||
|---|---|---|---|---|---|---|---|---|
|
pKi |
N |
pKi |
N |
pKi |
N |
pKi |
N |
|
|
DPH |
7.62±0.01 |
4 |
n.d. |
– |
n.d. |
– |
n.d. |
‐ |
|
1 |
5.62±0.03 |
3 |
6.58±0.04 |
48 |
7.59±0.01 |
42 |
7.60±0.01 |
45 |
|
2 |
<4 |
3 |
5.39±0.04[f] |
3 |
7.42±0.04 |
3 |
8.13±0.08 |
3 |
|
3 |
<5.5 |
2 |
7.33±0.05 |
3 |
5.25±0.05 |
3 |
5.00±0.05 |
3 |
|
4 |
<4.5 |
2 |
5.52±0.05 |
3 |
7.21±0.02 |
3 |
8.04±0.05 |
3 |
|
115 |
<4 |
2 |
6.63±0.06 |
3 |
5.59±0.03 |
3 |
7.03±0.07 |
3 |
|
116 |
<5 |
2 |
6.07±0.04 |
3 |
5.82±0.03 |
3 |
6.47±0.02 |
3 |
|
117 |
<5 |
2 |
6.12±0.04 |
3 |
6.19±0.01 |
3 |
6.36±0.03 |
3 |
|
118 |
5.91±0.03 |
2 |
6.44±0.02 |
3 |
6.65±0.04 |
3 |
6.33±0.03 |
3 |
|
119 |
6.06±0.03 |
2 |
6.80±0.02 |
3 |
7.14±0.01 |
3 |
6.78±0.01 |
3 |
|
120 |
6.71±0.02 |
2 |
7.28±0.04 |
3 |
7.45±0.02 |
3 |
7.16±0.04 |
3 |
|
121 |
6.30±0.01 |
2 |
6.50±0.09 |
3 |
5.38±0.01 |
3 |
5.33±0.03 |
3 |
|
122 |
6.52±0.01 |
2 |
6.73±0.05 |
3 |
5.29±0.06 |
3 |
4.65±0.06 |
3 |
|
123 |
<4.5 |
2 |
6.15±0.05 |
3 |
6.41±0.01 |
3 |
7.51±0.04 |
3 |
|
124 |
<5 |
2 |
6.24±0.02 |
3 |
6.97±0.03 |
3 |
6.62±0.02 |
3 |
|
125 |
<5.5 |
2 |
6.80±0.10 |
3 |
7.20±0.03 |
3 |
6.84±0.02 |
3 |
|
126 |
6.09±0.01 |
2 |
6.85±0.06 |
3 |
7.43±0.02 |
3 |
7.50±0.02 |
3 |
|
127 |
6.59±0.01 |
2 |
7.06±0.04 |
3 |
7.48±0.05 |
3 |
7.55±0.02 |
3 |
|
128 |
5.75±0.01 |
2 |
6.67±0.01 |
3 |
6.53±0.03 |
3 |
6.40±0.01 |
3 |
|
129 |
6.58±0.01 |
2 |
7.03±0.09 |
3 |
6.25±0.04 |
3 |
5.62±0.05 |
3 |
|
130 |
6.25±0.01 |
2 |
6.93±0.02 |
3 |
7.07±0.01 |
3 |
6.23±0.09 |
3 |
|
131 |
6.28±0.01 |
2 |
6.84±0.05 |
3 |
6.43±0.17 |
3 |
6.47±0.07 |
3 |
|
132 |
<4.5 |
2 |
5.75±0.10 |
3 |
6.80±0.01 |
3 |
6.84±0.01 |
3 |
|
133 |
<4.5 |
2 |
6.57±0.03 |
3 |
6.27±0.05 |
3 |
6.59±0.02 |
3 |
|
134 |
<5 |
2 |
6.55±0.07 |
3 |
6.69±0.02 |
3 |
6.18±0.03 |
3 |
|
135 |
<5.5 |
2 |
6.58±0.11 |
3 |
6.84±0.02 |
3 |
6.56±0.01 |
3 |
|
136 |
<5.5 |
2 |
6.95±0.02 |
3 |
7.00±0.01 |
3 |
6.70±0.01 |
3 |
|
141 |
<4 |
2 |
4.26±0.09 |
3 |
6.78±0.05 |
3 |
6.82±0.04 |
3 |
|
142 |
<4 |
2 |
<4 |
3 |
6.07±0.03 |
3 |
5.77±0.02 |
3 |
|
143 |
<4 |
2 |
4.98±0.09 |
3 |
6.58±0.08 |
3 |
8.14±0.01 |
3 |
|
144 |
<4 |
2 |
<4 |
3 |
6.09±0.01 |
3 |
5.28±0.06 |
3 |
|
145 |
<5 |
2 |
6.17±0.08 |
3 |
6.91±0.03 |
3 |
6.83±0.02 |
3 |
[a]Data represent mean values ± SEM from at least two independent experiments (N), each performed in triplicate. Radioligand competition binding experiments performed with [b][3H]mepyramine (hH1R, K d 4.5 nM, c=5 nM), [c][3H]tiotidine (hH2R, K d 19.7 nM, c=10 nM), [d][3H]Nα‐methylhistamine (hH3R, K d 8.6 nM, c=3 nM) or [e][3H]histamine (hH4R, K d 16.0 nM, c=15 nM) at membranes of Sf9 cells expressing [b]the hH1R plus RGS4, [c]the hH2R plus Gsαs, [d]the hH3R plus Gαi2 plus Gβ1γ2, [e]the hH4R plus Gαi2 plus Gβ1γ2. [f]Displacement of [3H]UR‐DE257 (hH2R, K d 31.3 nM, c=20 nM) instead of [3H]tiotidine; n.d.=not determined.