Specific inhibition of benzodiazepine receptor binding by some N-(indol-3-ylglyoxylyl)amino acid derivatives

J Med Chem. 1985 Apr;28(4):506-9. doi: 10.1021/jm00382a022.

Abstract

Several N-(indol-3-ylglyoxylyl)amino acid derivatives were synthesized and tested for their affinity for the benzodiazepine receptor in bovine cortical membranes. From these compounds, the N-[(5-chloro-, 5-bromo-, or 5-nitroindol-3-yl)glyoxylyl]glycine or -alanine esters were clearly the most potent, while the 5-methoxy analogues were considerably less active. Moreover, esters were more active than the corresponding acids. It is concluded that the affinity of these derivatives for the benzodiazepine receptor is profoundly dependent on amino acid molecular size, as well as the hydrophobic and electronic properties of the compounds.

MeSH terms

  • Alanine / analogs & derivatives
  • Alanine / chemical synthesis
  • Alanine / pharmacology
  • Amino Acids / chemical synthesis
  • Amino Acids / pharmacology*
  • Animals
  • Brain / metabolism
  • Cattle
  • Flunitrazepam / metabolism
  • Glycine / analogs & derivatives
  • Glycine / chemical synthesis
  • Glycine / pharmacology
  • In Vitro Techniques
  • Indoles / chemical synthesis
  • Indoles / pharmacology*
  • Receptors, GABA-A / drug effects*
  • Receptors, GABA-A / metabolism
  • Structure-Activity Relationship

Substances

  • Amino Acids
  • Indoles
  • Receptors, GABA-A
  • Flunitrazepam
  • Alanine
  • Glycine