2. Academic Validation
  3. (2-Arylethenyl)-1,3,5-triazin-2-amines as a novel histamine H4 receptor ligands

(2-Arylethenyl)-1,3,5-triazin-2-amines as a novel histamine H4 receptor ligands

  • Eur J Med Chem. 2015 Oct 20:103:238-51. doi: 10.1016/j.ejmech.2015.08.014.
Katarzyna Kamińska 1,  Julia Ziemba 1,  Joanna Ner 1,  Johannes Stephan Schwed 2,  Dorota Łażewska 1,  Małgorzata Więcek 1,  Tadeusz Karcz 1,  Agnieszka Olejarz 1,  Gniewomir Latacz 1,  Kamil Kuder 1,  Tim Kottke 2,  Małgorzata Zygmunt 3,  Jacek Sapa 3,  Janina Karolak-Wojciechowska 4,  Holger Stark 2,  Katarzyna Kieć-Kononowicz 5
Affiliations

Affiliations

  • 1 Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
  • 2 Heinrich-Heine-University, Institute of Pharmaceutical and Medicinal Chemistry, Universitaetsstr. 1, 40225 Duesseldorf, Germany.
  • 3 Department of Pharmacodynamics, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland.
  • 4 Institute of General and Ecological Chemistry, Technical University of Łódź, Żeromskiego 116, 90-924 Łódź, Poland.
  • 5 Department of Technology and Biotechnology of Drugs, Jagiellonian University Medical College, Medyczna 9, 30-688 Kraków, Poland. Electronic address: mfkonono@cyf-kr.edu.pl.
PMID: 26360048 DOI: 10.1016/j.ejmech.2015.08.014
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.

Keywords

1,3,5-Triazin-2-amines; 4-Methylpiperazines; Anti-inflammatory properties; Histamine H(4) receptor.

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