title: (2-Arylethenyl)-1,3,5-triazin-2-amines as a novel histamine H4 receptor ligands.
abstract: Within the constantly growing number of histamine H4 (H4R) receptor ligands there is a large group of azine derivatives. A series of novel compounds in the group of 4-methylpiperazine-1,3,5-triazine-2-amines were designed and obtained. Considered structures were modified at the triazine 6-position by introduction of variously substituted arylethenyl moieties. Their affinities to histamine H4 receptors were evaluated in radioligand binding assays with use of Sf9 cells, transiently expressing human H4R. Pharmacological studies results allowed to identify 4-[(E)-2-(3-chlorophenyl)ethenyl]-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (Ki = 253 nM) as the most potent compound in the present series.
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kamińska
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Julia
authors.initials: J
authors.lastname: Ziemba
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Ner
authors.affiliation: Heinrich-Heine-University, Institute of Pharmaceutical and Medicinal Chemistry, Universitaetsstr. 1, 40225 Duesseldorf, Germany.
authors.forename: Johannes Stephan
authors.initials: JS
authors.lastname: Schwed
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Dorota
authors.initials: D
authors.lastname: Łażewska
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Więcek
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Karcz
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Olejarz
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Gniewomir
authors.initials: G
authors.lastname: Latacz
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuder
authors.affiliation: Heinrich-Heine-University, Institute of Pharmaceutical and Medicinal Chemistry, Universitaetsstr. 1, 40225 Duesseldorf, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Kottke
authors.affiliation: Department of Pharmacodynamics, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Zygmunt
authors.affiliation: Department of Pharmacodynamics, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Sapa
authors.affiliation: Institute of General and Ecological Chemistry, Technical University of Łódź, Żeromskiego 116, 90-924 Łódź, Poland.
authors.forename: Janina
authors.initials: J
authors.lastname: Karolak-Wojciechowska
authors.affiliation: Heinrich-Heine-University, Institute of Pharmaceutical and Medicinal Chemistry, Universitaetsstr. 1, 40225 Duesseldorf, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
authors.affiliation: Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland. Electronic address: mfkonono@cyf-kr.edu.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kieć-Kononowicz
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D051379:Mice; D015394:Molecular Structure; D011869:Radioligand Assay; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011968:Receptors, Histamine / Q000378:metabolism*; D000074040:Receptors, Histamine H4; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; C418607:HRH4 protein, human; C498829:Hrh4 protein, mouse; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D014227:Triazines
keywords: 1,3,5-Triazin-2-amines; 4-Methylpiperazines; Anti-inflammatory properties; Histamine H(4) receptor