Triazine compounds as antagonists at Bv8-prokineticin receptors

J Med Chem. 2008 Dec 11;51(23):7635-9. doi: 10.1021/jm800854e.

Abstract

On the basis of a Janssen's patent, we approached a new synthesis of some 1,3,5-triazin-4,6-diones as potential non peptidic prokineticin receptor antagonists, containing the following substitutions: (N(1) and N(5) link a 4-methoxybenzyl and a 4-ethylbenzyl, respectively; C(2) can link an amino-ethyl-guanidine (reference compound 1) or an ethylendiamine (2) or an amino-ethyl-amino-2-imidazoline (3). New compounds were assessed for PKR1 and PKR2 affinity. Antagonist properties were evaluated as inhibition of 1 nM Bv8-induced intracellular Ca2+ mobilization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites / drug effects
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design
  • Gastrointestinal Hormones / chemistry
  • Humans
  • Ligands
  • Molecular Structure
  • Neuropeptides / chemistry
  • Receptors, G-Protein-Coupled / antagonists & inhibitors*
  • Receptors, Peptide / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Triazines / chemical synthesis
  • Triazines / chemistry
  • Triazines / pharmacology*

Substances

  • Gastrointestinal Hormones
  • Ligands
  • Neuropeptides
  • PROK2 protein, human
  • PROKR1 protein, human
  • PROKR2 protein, human
  • Receptors, G-Protein-Coupled
  • Receptors, Peptide
  • Triazines
  • Calcium