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

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.