Acidic elements in histamine H 3 receptor antagonists

Abstract

Antagonists of the human histamine H 3 receptor ( hH 3R) often contain a second basic moiety, which is well known to boost affinity on this histamine receptor subtype. Here, we prepared compounds with acidic moieties of different p K a values to figure out that the hH 3R tolerates these functionalities when added to a common pharmacophore blueprint. Depending on the acidic, electronic and steric features the designed ligands showed hH 3R affinities in the nanomolar concentration range. Additionally, selected ligands were tested but failed as dual acting hH 3R/ hPPAR (human peroxisome proliferator-activated receptor) ligands.