title: Discovery of novel lead in the group of N-substituted piperazine ether derivatives with potential histamine H3 receptor activity.
abstract: The search for novel lead from the group of various substituted N-piperazine ether derivatives was performed. Acyl- and pyridylpiperazine ethyl/propyl ethers were obtained via three different synthetic pathways. Affinity to histamine H3 receptor was established, as well as, for selected compounds, selectivity towards histamine H4R. Docking studies to the histamine H3R homology model strengthened the position of (4-(3-(4-(3-chlorobenzoyl)piperazin-1- yl)propoxy)phenyl)(cyclopropyl)methanone (compound 26) as a novel lead for further studies on histamine H3 receptor antagonist/inverse agonist.
authors.forename: Kamil J
authors.initials: KJ
authors.lastname: Kuder
authors.forename: Marta
authors.initials: M
authors.lastname: Stachnik
authors.forename: Walter
authors.initials: W
authors.lastname: Schunack
authors.forename: Ewa
authors.initials: E
authors.lastname: Szymańska
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University, Medical College, Krakow, 30-688, Poland. mfkonono@cyf-kr.edu.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kieć-Kononowicz
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D016466:CHO Cells; D003412:Cricetulus; D055808:Drug Discovery / Q000379:methods*; D004987:Ethers; D017442:Histamine Agonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D054828:Histamine H3 Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism; D011968:Receptors, Histamine / Q000737:chemistry / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000737:chemistry* / Q000235:genetics; D000074040:Receptors, Histamine H4
chemical_list: C000596533:4-(3-(4-(3-chlorobenzoyl)piperazin-1-yl)propoxy)phenyl)(cyclopropyl)methanone; D004987:Ethers; C418607:HRH4 protein, human; D017442:Histamine Agonists; D054828:Histamine H3 Antagonists; D008024:Ligands; D010879:Piperazines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D018100:Receptors, Histamine H3; D000074040:Receptors, Histamine H4