Synthesis of dibenzodioxazocines and their effects on cholinesterases and muscarinic cholinergic receptors

Acta Biochim Biophys Hung. 1989;24(1-2):129-42.

Abstract

A new family of tricyclic compounds, the dibenzodioxazocines were synthesized. These compounds were the following: 2-chloro-12-(2-piperidino-ethyl)-dibenzo d,g 1,3,6 dioxazocine hydrochloride: EGYT-2347, 2-chloro-12-(3-dimethylamino-2-methyl-propyl)-dibenzo [d,g] [1,3,6]-dibenzodioxazocine hydrochloride: EGYT-2509, 2-chloro-12-(3-dimethylamino-propyl)-dibenzo [d,g] [1,3,6] dioxazocine-maleate: EGYT-2474 and 2-chloro-12-2-(4-methyl-piperazino)-ethyl-dibenzo [d,g] [1,3,6]-dioxazocine-dihydrochloride: EGYT-2541. These compounds are inhibitors of both butyryl- and acetylcholinesterase to and they exhibited relatively good anticholinergic properties in receptor binding experiments. The most selective inhibitor of butyrylcholinesterase is the compound EGYT-2347 (Ki = 1.5 x 10(-7) M) which strongly binds to rat brain muscarinic cholinergic receptor (KD = 4.1 x 10(-8) M).

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Cattle
  • Cholinesterase Inhibitors*
  • Dibenzoxazepines / chemical synthesis
  • Dibenzoxazepines / metabolism
  • Dibenzoxazepines / pharmacology*
  • Female
  • Guinea Pigs
  • Ileum / drug effects
  • Ileum / metabolism
  • In Vitro Techniques
  • Kinetics
  • Male
  • Rats
  • Receptors, Muscarinic / drug effects*
  • Receptors, Muscarinic / metabolism
  • Structure-Activity Relationship

Substances

  • Cholinesterase Inhibitors
  • Dibenzoxazepines
  • Receptors, Muscarinic
  • 2-chloro-12-(2-piperidinoethyl)dibenzo(d,g)-1,3,6-dioxazocine
  • EGYT 2509