Alkyl derivatives of 1,3,5-triazine as histamine H4 receptor ligands

Abstract This study focuses on the design, synthesis, molecular modeling and biological evaluation of a novel group of alkyl-1,3,5-triazinyl-methylpiperazines. New compounds were synthesized and their affinities for human histamine H 4 receptor (hH 4 R) were evaluated. Among them, 4-(cyclohexylmethyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine ( 14 ) exhibited hH 4 R affinity with a K i of 160 nM and behaved as antagonist in functional assays: the cellular aequorin-based assay (IC 50  = 32 nM) and [ 35 S]GTPγS binding assay (pK b  = 6.67). In addition, antinociceptive activity of 14 in vivo was observed in Formalin test (in mice) and in Carrageenan-induced acute inflammation test (in rats).