Synthesis and properties of N-methyl and N-phenyl derivatives of 1,4-dioxo-1,2,3,4-tetrahydropyrido[3,4-d]pyridazines.
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.
Sladowska
H
H
Department of Chemistry of Drugs, Wroclaw Medical University, Wroclaw, Poland.
Sokolowska
M
M
Sabiniarz
A
A
Filipek
B
B
Sapa
J
J
D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D004357:Drug Synergism; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D007202:Indicators and Reagents; D007928:Lethal Dose 50; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000187:drug effects; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D013874:Thiopental / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D006993:Hypnotics and Sedatives; D007202:Indicators and Reagents; D011724:Pyridazines; D011725:Pyridines; D013874:Thiopental