Alkyl derivatives of 1,3,5-triazine as histamine H 4 receptor ligands.

Authors :: Łażewska D
Mogilski S
Hagenow S
Kuder K
Głuch-Lutwin M
Siwek A
Więcek M
Kaleta M
Seibel U
Buschauer A
Filipek B
Stark H
Kieć-Kononowicz K
Source :: Bioorganic & medicinal chemistry [Bioorg Med Chem] 2019 Apr 01; Vol. 27 (7), pp. 1254-1262. Date of Electronic Publication: 2019 Feb 12.
Publication Year :: 2019
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 <subscript>4</subscript> receptor (hH <subscript>4</subscript> R) were evaluated. Among them, 4-(cyclohexylmethyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (14) exhibited hH <subscript>4</subscript> R affinity with a K <subscript>i</subscript> of 160 nM and behaved as antagonist in functional assays: the cellular aequorin-based assay (IC <subscript>50</subscript>  = 32 nM) and [ <superscript>35</superscript> S]GTPγS binding assay (pK <subscript>b</subscript>  = 6.67). In addition, antinociceptive activity of 14in vivo was observed in Formalin test (in mice) and in Carrageenan-induced acute inflammation test (in rats).<br /> (Copyright © 2019 Elsevier Ltd. All rights reserved.)