| Literature DB >> 24996140 |
Dorota Łażewska1, Małgorzata Więcek1, Joanna Ner1, Katarzyna Kamińska1, Tim Kottke2, J Stephan Schwed2, Małgorzata Zygmunt3, Tadeusz Karcz1, Agnieszka Olejarz1, Kamil Kuder1, Gniewomir Latacz1, Marek Grosicki1, Jacek Sapa3, Janina Karolak-Wojciechowska4, Holger Stark5, Katarzyna Kieć-Kononowicz6.
Abstract
A series of novel 2-amino-4-(4-methylpiperazin-1-yl)-1,3,5-triazine derivatives with different aryl substituents in the 6-position was designed, synthesized and evaluated for histamine H4 receptor (H4R) affinity in Sf9 cells expressing human H4R co-expressed with G-protein subunits. Triazine derivative 8 with a 6-(p-chlorophenyl) substituent showed the highest affinity with hH4R Ki value of 203 nM and was classified as an antagonist in cAMP accumulation assay. This compound, identified as a new lead structure, demonstrated also anti-inflammatory properties in preliminary studies in mice (carrageenan-induced edema test) and neither possessed significant antiproliferative activity, nor modulated CYP3A4 activity up to concentration of 25 μM. In order to discuss structure-activity relationships molecular modeling and docking studies were undertaken.Entities:
Keywords: 2,4,6-Trisubstituted 1,3,5-triazines; 4-Methylpiperazines; Anti-inflammatory properties; Histamine H(4) receptor
Mesh：
Substances：
Year: 2014 PMID： 24996140 DOI： 10.1016/j.ejmech.2014.06.032
Source DB: PubMed Journal: Eur J Med Chem ISSN： 0223-5234 Impact factor: 6.514