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

Abstract 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 (H 3 ) receptor antagonist. Additional optimization of 6h led to the identification of compounds 11i – k with K i  ⩽ 0.5 nM and good in vivo activity.