The synthesis and structure–activity relationship of 4-benzimidazolyl-piperidinylcarbonyl-piperidine analogs as histamine H3 antagonists

A structure–activity relationship study of the lead piperazinylcarbonylpiperidine compound 3 resulted in the identification of 4-benzimidazolyl-piperidinylcarbonyl-piperidine 6h as a histamine-3 (H3) receptor antagonist. Additional optimization of 6h led to the identification of compounds 11i–k with Ki ⩽ 0.5 nM and good in vivo activity.

Graphical abstractA structure–activity relationship study of the lead piperazinylcarbonylpiperidine compound 3 has resulted in the identification of 4-benzimidazolyl-piperidinylcarbonyl-piperidine 6h as a histamine-3 (H3) receptor antagonist. Additional optimization of 6h led to the identification of compounds 11i–k with Ki < 0.5 nM and good in vivo activity.Figure optionsDownload full-size imageDownload as PowerPoint slide