Aryl-1,3,5-triazine derivatives as histamine H-4 receptor ligands

作者：Lazewska Dorota; Wicek Maigorzata; Ner Joanna; Kamiriska Katarzyna; Kottke Tim; Schwed J Stephan; Zygmunt Malgorzata; Karcz Tadeusz; Olejarz Agnieszka; Kuder Kamil; Latacz Gniewomir; Grosicki Marek; Sapa Jacek; Karolak Wojciechowska Janina; Stark Holger; Kiee Kononowicz Katarzyna^*

来源：European Journal of Medicinal Chemistry, 2014, 83: 534-546.

DOI：10.1016/j.ejmech.2014.06.032

• Histamine H-4 receptor
• 4-Methylpiperazines
• 2,4,6-Trisubstituted 1,3,5-triazines
• Anti-inflammatory properties

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 H-4 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 hH(4)R K-i 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 mu M. In order to discuss structure activity relationships molecular modeling and docking studies were undertaken.

• 出版日期2014-8-18