Synthesis and biological activities of a series of homo-or substituted piperidine unsymmetrical diethers are described. The novel compounds were evaluated for histamine H3 receptor binding affinities at recombinant human H3 receptor stably expressed in HEK- 293 cells. All diethers showed in vitro affinities in nanomolar concentration range. The most potent compounds are 1-[3-(3-(4-chlorophenoxy) propoxy) propyl]-3-methylpiperidine 11 ( ...