ABSTRACT
2-(1-Piperidino)- and 2-(4-methyl-1-piperazinyl)-6-methyl-3,4-pyridinedicarboximides (1, 2) react with N-phenylhydrazine yielding N-phenylamino-3,4-pyridinedicarboximides (7, 8). The same reaction with 1,6-dimethyl-2-oxo-1,2-dihydro- and 2-chloro-6-methyl-3,4-pyridinedicarboximides (3, 17) gives the salts of the corresponding N-phenylpyridopyridazines with phenylhydrazine (13, 18), which transform into N-phenylaminoimides (14, 19) during boiling in 80% acetic acid. Compounds 7, 8 and 14 isomerize to the corresponding 2-phenyl-1,4-dioxo(1,4,5-trioxo)-1,2,3,4-tetra(1,2,3,4,5,6-hexa) hydropyrido[3,4-d]pyridazines (9, 10, 15) under the influence of heating in alcoholic solution of C2H5ONa or CH3ONa. Only in the case of imide 19 are 2- and 3-phenyl isomers (20 and 21) formed under these conditions. Some of the obtained compounds were pharmacologically active.
Subject(s)
Pyridazines/chemistry , Pyridazines/chemical synthesis , Animals , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/chemistry , Female , Injections, Intraperitoneal , Lethal Dose 50 , Male , Mice , Molecular Structure , Motor Activity/drug effects , Pyridazines/pharmacology , Pyridazines/toxicity , Rats , Rats, Wistar , Structure-Activity RelationshipABSTRACT
Synthesis of 2-substituted N-(4-phenyl-1 piperazinyl)propyl(butyl)- and N-2-hydroxy-3[4-phenyl(2-pyrimidinyl)-1-piperazinyl]propyl-6-methyl-3,4- pyridinedicarboximides [VI-XIV] is described. Some of them displayed depressive action on the central nervous system.
Subject(s)
Heterocyclic Compounds, 1-Ring/chemical synthesis , Imides/chemical synthesis , Pyrimidines/chemical synthesis , Animals , Blood Pressure/drug effects , Central Nervous System/drug effects , Drug Evaluation, Preclinical , Female , Heterocyclic Compounds, 1-Ring/pharmacology , Imides/pharmacology , Lethal Dose 50 , Male , Mice , Motor Activity/drug effects , Pyrimidines/pharmacology , Rats , Rats, WistarABSTRACT
The synthesis of N-aryl(pyrimidinyl)piperazinylalkyl(hydroxyalkyl) derivatives of 1,4-dioxo(1,4,5-trioxo)-1,2,3,4-tetra (and 1,2,3,4,5,6-hexa)hydropyrido[3,4-d]pyridazines is described. Some of them show biological activity in the preliminary pharmacological tests.
Subject(s)
Psychotropic Drugs/chemical synthesis , Pyridazines/chemical synthesis , Pyridines/chemical synthesis , Animals , Anti-Anxiety Agents/chemical synthesis , Anti-Anxiety Agents/pharmacology , Anticonvulsants/chemical synthesis , Anticonvulsants/pharmacology , Drug Interactions , Female , Hemodynamics/drug effects , Lethal Dose 50 , Magnetic Resonance Spectroscopy , Male , Mice , Motor Activity/drug effects , Pain Measurement/drug effects , Postural Balance/drug effects , Psychotropic Drugs/pharmacology , Pyridazines/pharmacology , Pyridines/pharmacology , Rats , Rats, Wistar , Spectrophotometry, InfraredABSTRACT
2-(1-Piperidino)- and 2-(4-methyl-1-piperazinyl)-6-methyl-3, 4-pyridinedicarboximides (1,2) react with CH3NH-NH2 yielding 3-methyl derivatives of the corresponding 1,4-dioxo-1,2,3,4-tetrahydropyrido[3,4-d] pyridazines (4,5). The same reaction with 1,6-dimethyl-2-oxo-1,2-dihydro-3,4- pyridinedicarboximide (3) affords 2-methyl derivative of the corresponding 1,4,5-trioxo-1,2,3,4,5,6- hexahydropyrido[3,4-d]pyridazine (8. Compounds 4,5 and 8 were transformed into their N-arylpiperazinylalkyl derivatives (13-18) on two ways. Some of them were active pharmacologically.
