Mepyramine–JNJ7777120-hybrid compounds show high affinity to hH1R, but low affinity to hH4R

In literature, a synergism between histamine H1 and H4 receptor is discussed. Furthermore, it was shown, that the combined application of mepyramine, a H1 antagonist and JNJ7777120, a H4 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 H1 and one H4 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 hH1R and hH4R. The new compounds revealed (high) affinity to hH1R, but showed only low affinity to hH4R. Additionally, we performed molecular dynamic studies for some selected compounds at hH1R, in order to obtain information about the binding mode of these compounds on molecular level.

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