Synthesis and properties of N-methyl and N-phenyl derivatives of 1,4-dioxo-1,2,3,4-tetrahydropyrido[3,4-d]pyridazines

Boll Chim Farm. 2004 Jun;143(5):211-8.

Abstract

2-Methoxy- and 2-ethoxy-6-methyl-3,4-pyridinedicarboximides (XI, XII) reacted with N-methylhydrazine giving 2- and 3-methyl derivatives of the appropriate 1,4-dioxo-1,2,3,4-tetrahydropyrido[3,4-d]pyridazines (XV, XIII and XVI, XIV). In both cases 3-methyl isomer (XIII, XIV) was formed in higher yield than 2-methyl derivative (XV, XVI). Reaction of the imide XII with N-phenylhydrazine gave the salts of the suitable N-phenyldihydropyrido[3,4d]pyridazines with NH2-NHC6H5 (XXI and XXII) which transformed into N-phenylaminoimide (XXIII) during the boiling in 80% CH3COOH. Imide XXIII isomerized to the appropriate 2-phenyl and 3-phenylpyrido[3,4-d]pyridazines (XXIV - main reaction product and XXV) under the influence of heating in ethanolic solution of C2H5ONa. Some of N-phenylpiperazinylhydroxyalkyl(alkyl) derivatives of compound XXIV (XXVII, XXVIII) were pharmacologically active.

MeSH terms

  • Analgesics, Non-Narcotic / chemical synthesis*
  • Analgesics, Non-Narcotic / pharmacology*
  • Analgesics, Non-Narcotic / toxicity
  • Animals
  • Drug Synergism
  • Hypnotics and Sedatives / chemical synthesis*
  • Hypnotics and Sedatives / pharmacology*
  • Hypnotics and Sedatives / toxicity
  • Indicators and Reagents
  • Lethal Dose 50
  • Mice
  • Motor Activity / drug effects
  • Pain Measurement / drug effects
  • Pyridazines / chemical synthesis*
  • Pyridazines / pharmacology*
  • Pyridazines / toxicity
  • Pyridines / chemical synthesis*
  • Pyridines / pharmacology*
  • Pyridines / toxicity
  • Thiopental / pharmacology

Substances

  • Analgesics, Non-Narcotic
  • Hypnotics and Sedatives
  • Indicators and Reagents
  • Pyridazines
  • Pyridines
  • Thiopental