Variations of acidic functions at position 2 and substituents at positions 4, 5 and 6 of the indole moiety and their effect on NMDA-glycine site affinity

Eur J Med Chem. 2003 Oct;38(10):855-65. doi: 10.1016/j.ejmech.2003.07.001.

Abstract

The synthetic procedures to obtain indole derivatives with different acidic functions at position 2 of the indole are reported. The synthesised and tested derivatives comprise 5-tetrazolyl, 1,3,4-oxadiazol-5-yl-2-one, and indole-2-carboxylic acid amides with 5-aminotetrazole, methanesulphonamide and trifluoromethanesulphonamide moieties. The binding affinity was evaluated using [3H]MDL 105,519 and pig cortical brain membranes. In general, compounds with acidic functions different from a carboxylic acid moiety are less potent than indole-2-carboxylic acid derivatives. Also, the 4,6-dichloro substitution pattern was compared to 5-tert-butyl derivatives and compounds not substituted in the benzene moiety of the indole, indicating that the affinity increases from 5-tert-butyl over unsubstituted to 4,6-dichloro substituted derivatives.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cell Membrane / chemistry
  • Cerebral Cortex / chemistry
  • Glycine
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Inhibitory Concentration 50
  • Models, Molecular
  • Radioligand Assay
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / chemistry*
  • Structure-Activity Relationship
  • Swine

Substances

  • Indoles
  • MDL 105519
  • Receptors, N-Methyl-D-Aspartate
  • Glycine