Piperidine variations in search for non-imidazole histamine H3 receptor ligands Original Research Article

Synthesis and biological evaluation of the novel histamine H3 receptor ligands is described. Two series of ethers (aliphatic and aromatic) have been prepared by four different methods. Compounds were evaluated for their affinities at recombinant human H3 receptor stably expressed in CHO cells. The ethers show from low to moderate in vitro affinities in nanomolar concentration range. The most potent compound was the 1-[3-(4-tert-butylphenoxy)propyl]-4-piperidino-piperidine 16 (hH3R Ki = 100 nM). Several members of the new series investigated under in vivo conditions, proved to be inactive.