Synthesis of some 2-aryl-1,2,4-triazolo[1,5-c][1,3]benzoxazin-5-ones as tools to define the essential pharmacophoric descriptors of a benzodiazepine receptor ligand

J Med Chem. 1995 Jun 9;38(12):2196-201. doi: 10.1021/jm00012a020.

Abstract

The synthesis and benzodiazepine receptor (BZR) affinity of some 1,2,4-triazolo[1,5-c][1,3]benzoxazin-5-ones, 2-22, are reported. Compounds 2-22 are devoid of the proton donor group, which according to a BZR schematic model was one of the pharmacophoric descriptors for receptor-ligand interaction. The binding data show that 2-(2-fluorophenyl)-9-chloro-1,2,4-triazolo[1,5-c][1,3]benzoxazin-5 -one (12) and some other compounds display nanomolar BZR affinity, indicating that the hydrogen donor group is not essential for the anchoring of 6,6,5-tricyclic systems to the BZR but only affects the potency of a ligand.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Cattle
  • Flunitrazepam / metabolism
  • Ligands
  • Oxazines / chemical synthesis*
  • Oxazines / chemistry
  • Oxazines / pharmacology
  • Receptors, GABA-A / drug effects*
  • Receptors, GABA-A / metabolism
  • Structure-Activity Relationship
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Ligands
  • Oxazines
  • Receptors, GABA-A
  • gamma-Aminobutyric Acid
  • Flunitrazepam