Synthesis and structure–activity relationships of indole and benzimidazole piperazines as histamine H4 receptor antagonists

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Abstract

We describe the structure–activity relationships for a series of ligands structurally related to the recently identified (5-chloro-1H-indol-2-yl)-(4-methyl-piperazin-1-yl)-methanone (1) as histamine H4 receptor (H4R) antagonists. Furthermore, we identified related benzimidazoles as novel lead compounds for the H4R. The ligands have been evaluated by radioligand displacement studies and functional assays for their interaction with both the human histamine H3 and H4 receptors and exhibit pKi values up to 7.5 at the human H4R.

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Acknowledgements

This work was supported in part (N.T.) by Scientific Human Resources Development (BAYG NATO-B2) with financial aid from The Scientific and Technical Research Council of Turkey (TUBITAK). The cells stably expressing the human histamine H3Rs and H4Rs were a gift from Dr. T. Lovenberg (Johnson and Johnson Pharmaceutical Research and Development, L.L.C., San Diego, USA).

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