Studies on annelated 1,4-benzothiazines and 1,5-benzothiazepines. II. Synthesis of new series of 1- or 2-substituted 4H-s-triazolo[3,4-c]-1,4-benzothiazines and related compounds with potential CNS activity

Farmaco Sci. 1987 Jan;42(1):43-60.

Abstract

New series of 1- or 2-substituted 4H-s-triazolo[3,4-c]-1,4-benzothiazines have been prepared. The 1-substituted products were obtained starting from 3-hydrazino-2H-1,4-benzothiazine derivatives (III) by treatment with chloroacethyl chloride followed by cyclization of the resulting chloroacethylderivatives into the chloromethyltriazolobenzothiazines (IV a-e), which were then reacted with the appropriate amines to give the desired compounds (V a-n). Other 1-substituted compounds were prepared by ring closure of (III) with cyanogen bromide, affording 1-amino-4H-s-triazolo [3,4-c]-1,4-benzothiazines (XI a-e). The 2-substituted compounds (VIII) were prepared from 2,4-dihydro-1H-s-triazolo [3,4-c]-1,4-benzothiazin-1-ones (VII), synthesized from (I) by reaction with ethyl carbazate. The aminoalkyl side chain was introduced into (VII) in two steps: first by treatment with 1-bromo-3-chloropropane, then by refluxing the resulting product with the appropriate amine. Some 4H-tetrazolo[5,1-c]-1,4-benzothiazines (XII) were also synthesized from (III). Preliminary pharmacological data on the CNS activity of the synthesized tricyclic compounds are reported.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / chemical synthesis
  • Central Nervous System Agents / chemical synthesis*
  • Central Nervous System Agents / pharmacology
  • Chemical Phenomena
  • Chemistry
  • Lethal Dose 50
  • Magnetic Resonance Spectroscopy
  • Male
  • Mice
  • Motor Activity / drug effects
  • Spectrophotometry, Infrared
  • Thiazines / chemical synthesis*
  • Thiazines / pharmacology
  • Thiazines / toxicity
  • Triazoles / chemical synthesis*
  • Triazoles / pharmacology
  • Triazoles / toxicity

Substances

  • Anticonvulsants
  • Central Nervous System Agents
  • Thiazines
  • Triazoles