Spatial requirements of the antagonist binding site of the NK2 receptor

Bioorg Med Chem Lett. 2001 Mar 26;11(6):819-22. doi: 10.1016/s0960-894x(01)00074-9.

Abstract

Computer-aided modelling has been used to identify a putative antagonist binding site in the tachykinin NK2 receptor. In order to validate the implied spatial requirements for this region, a series of compounds, based on the potent antagonist GR 149861 have been synthesised and their binding affinities established. Our findings suggest the presence of a large hydrophobic cavity in the putative binding crevice of GR 149861.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Indoles / chemistry*
  • Indoles / pharmacology
  • Methylurea Compounds / chemistry
  • Methylurea Compounds / pharmacology
  • Models, Molecular
  • Molecular Conformation
  • Morpholines / chemistry
  • Morpholines / pharmacology
  • Piperidines / chemistry*
  • Piperidines / pharmacology
  • Protein Conformation
  • Receptors, Neurokinin-2 / antagonists & inhibitors
  • Receptors, Neurokinin-2 / chemistry*
  • Structure-Activity Relationship

Substances

  • GR 149861
  • Indoles
  • Methylurea Compounds
  • Morpholines
  • Piperidines
  • Receptors, Neurokinin-2
  • SR 144190