title: Mepyramine-JNJ7777120-hybrid compounds show high affinity to hH(1)R, but low affinity to hH(4)R.
abstract: In literature, a synergism between histamine H(1) and H(4) receptor is discussed. Furthermore, it was shown, that the combined application of mepyramine, a H(1) antagonist and JNJ7777120, a H(4) receptor ligand leads to a synergistic effect in the acute murine asthma model. Thus, the aim of this study was to develop new hybrid ligands, containing one H(1) and one H(4) pharmacophor, connected by an appropriate spacer, in order to address both, H(1)R and H(4)R. Within this study, we synthesized nine hybrid compounds, which were pharmacologically characterized at hH(1)R and hH(4)R. The new compounds revealed (high) affinity to hH(1)R, but showed only low affinity to hH(4)R. Additionally, we performed molecular dynamic studies for some selected compounds at hH(1)R, in order to obtain information about the binding mode of these compounds on molecular level.
authors.affiliation: Department of Pharmaceutical/Medicinal Chemistry I, Institute of Pharmacy, University of Regensburg, D-93040 Regensburg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Wagner
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Wittmann
authors.forename: Sigurd
authors.initials: S
authors.lastname: Elz
authors.forename: Andrea
authors.initials: A
authors.lastname: Strasser
mesh_terms: D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008958:Models, Molecular; D010879:Piperazines / Q000494:pharmacology*; D011738:Pyrilamine / Q000494:pharmacology*; D011969:Receptors, Histamine H1 / Q000187:drug effects*
chemical_list: D006634:Histamine H1 Antagonists; D007211:Indoles; D010879:Piperazines; D011969:Receptors, Histamine H1; C484309:1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine; D011738:Pyrilamine