Mepyramine-JNJ7777120-hybrid compounds show high affinity to hH(1)R, but low affinity to hH(4)R.

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Wagner E, Wittmann HJ, Elz S, Strasser A

Mepyramine-JNJ7777120-hybrid compounds show high affinity to hH(1)R, but low affinity to hH(4)R.

Bioorg Med Chem Lett. 2011 Nov 1;21(21):6274-80. doi: 10.1016/j.bmcl.2011.09.001. Epub 2011 Sep 8.

PubMed ID
21944853 [ View in PubMed
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Abstract

In literature, a synergism between histamine H(1) and H(4) receptor is discussed. Furthermore, it was shown, that the combined application of mepyramine, a H(1) antagonist and JNJ7777120, a H(4) receptor ligand leads to a synergistic effect in the acute murine asthma model. Thus, the aim of this study was to develop new hybrid ligands, containing one H(1) and one H(4) pharmacophor, connected by an appropriate spacer, in order to address both, H(1)R and H(4)R. Within this study, we synthesized nine hybrid compounds, which were pharmacologically characterized at hH(1)R and hH(4)R. The new compounds revealed (high) affinity to hH(1)R, but showed only low affinity to hH(4)R. Additionally, we performed molecular dynamic studies for some selected compounds at hH(1)R, in order to obtain information about the binding mode of these compounds on molecular level.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AstemizoleHistamine H1 receptorKi (nM)2.09N/AN/ADetails
DiphenhydramineHistamine H1 receptorKi (nM)14.79N/AN/ADetails
MepyramineHistamine H1 receptorKi (nM)4.47N/AN/ADetails