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

Bioorg Med Chem. 2019 Apr 1;27(7):1254-1262. doi: 10.1016/j.bmc.2019.02.020. Epub 2019 Feb 12.

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 H4 receptor (hH4R) were evaluated. Among them, 4-(cyclohexylmethyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine (14) exhibited hH4R affinity with a Ki of 160 nM and behaved as antagonist in functional assays: the cellular aequorin-based assay (IC50 = 32 nM) and [35S]GTPγS binding assay (pKb = 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).

Keywords: 1,3,5-Triazine; Docking; Histamine H(4) ligands; Histamine H(4) receptors; Pain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / chemical synthesis
  • Analgesics / chemistry
  • Analgesics / pharmacology*
  • Animals
  • Carrageenan
  • Dose-Response Relationship, Drug
  • Formaldehyde
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Ligands
  • Mice
  • Molecular Structure
  • Rats
  • Receptors, Histamine H4 / antagonists & inhibitors*
  • Receptors, Histamine H4 / metabolism
  • Structure-Activity Relationship
  • Triazines / chemical synthesis
  • Triazines / chemistry
  • Triazines / pharmacology*

Substances

  • Analgesics
  • Ligands
  • Receptors, Histamine H4
  • Triazines
  • Formaldehyde
  • Carrageenan