Zusammenfassung
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 ...
Zusammenfassung
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, H1R and H4R. 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. (C) 2011 Elsevier Ltd. All rights reserved.
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