Geometrically constrained analogues of N-benzylindolylglyoxylylamides: [1, 2, 4]triazino[4, 3-a]benzimidazol-4(10H)-one derivatives as potential new ligands at the benzodiazepine receptor

Arch Pharm (Weinheim). 2003 Sep;336(9):413-21. doi: 10.1002/ardp.200300788.

Abstract

A series of 3-benzylamino-and 3-arylalkylaminocarbonyl [1, 2, 4]triazino [4, 3-a]benzimidazoles 1-12 were synthesized and biologically assayed as geometrically constrained analogues of N-benzylindolylglyoxylylamides II, which are high affinity ligands at the benzodiazepine receptor (BzR). The intermediate 3-ethoxycarbonyl [1, 2, 4]triazino [4, 3-a]benzimidazol-4(10H)-one 14 and its N(10)-methyl analogue 15 closely related to 3-alkoxycarbonyl-beta-carbolines I were also investigated. The title compounds exhibited a lower affinity compared with the corresponding indolylglyoxylylamide derivatives II. Attempts were made to rationalize these results taking into account the possible tautomeric equilibria involving these ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzimidazoles / chemical synthesis*
  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacology
  • Binding, Competitive
  • Brain / metabolism
  • Cattle
  • In Vitro Techniques
  • Indoles / chemistry*
  • Ligands
  • Radioligand Assay
  • Receptors, GABA-A / drug effects*
  • Receptors, GABA-A / metabolism
  • Triazines / chemical synthesis*
  • Triazines / chemistry
  • Triazines / pharmacology

Substances

  • (1, 2, 4)triazino(4, 3-a)benzimidazol-4(10H)-one
  • Benzimidazoles
  • Indoles
  • Ligands
  • Receptors, GABA-A
  • Triazines
  • N-(indol-3-ylglyoxylyl)benzylamine