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.