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.

Synthesis and properties of tetra(hexa)hydropyrazolo [1,2-a]pyrido[3,4-d]pyridazine derivatives.

The synthesis of tetra(hexa)hydropyrazolo[1,2-a]pyrido[3,4-d]pyridazine derivatives (14-21) and the results of pharmacological screening are described in this paper. All compounds tested were non-toxic and showed a significant analgesic action. The analgesic effects were associated with the suppression of the spontaneous locomotor activity. Furthermore most of the synthesized compounds displayed a weak antimycobacterial action in the preliminary screening.

Synthesis and properties of 2-(4-substituted)butyl derivatives of some 2,3-dihydro-1,3-dioxo-1H-pyrrolo[3,4-c]pyridines.

The synthesis of 2-(4-substituted)butyl derivatives of 4-alkoxy-2,3-dihydro-6-methyl-1,3-dioxo-1H-pyrrolo[3,4-c]pyridine (10-15) and the results of preliminary pharmacological screening are described in this paper. All the compounds tested showed a strong analgesic action, suppressed spontaneous locomotor activity and prolonged barbiturate sleep. Except 10, all significantly decreased systolic and diastolic blood pressure.

Synthesis and pharmacological properties of 1-(4-substituted)butyl derivatives of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimi dine-5 -carboxylic acid.

The synthesis of 1-(4-substituted)butyl derivatives of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimid ine-5- carboxylic acid and the results of the preliminary pharmacological screening are described in this paper. Some of them showed a weak analgesic action and caused suppression of the spontaneous locomotor activity of mice.

Investigations on the synthesis and pharmacological properties of amides of 7-methyl-3-phenyl-1-[2-hydroxy-3-(4-phenyl-1-piperazinyl)propyl]-2,4- dioxo-1,2,3,4-tetrahydropyrido[2,3-d]-pyrimidine-5-carboxylic acid.

Synthesis of amides of 7-methyl-3-phenyl-2,4-dioxo-1,2,3,4- tetrahydropyrido[2,3-d]pyrimidine-5-carboxylic acid (6-10) and their 1-[2-hydroxy-3(4-phenyl-1-piperazinyl)propyl] derivatives (11-15) are described. Some of them displayed strong analgesic activity.

Investigations on the synthesis and properties of N-phenyl derivatives of 1,4-dioxo(1,4,5-trioxo)-1,2,3,4-tetra(1,2,3,4,5,6-hexa) hydropyrido-[3,4-d]pyridazines and allied compounds.

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.

Investigations on the synthesis and properties of 4-aminosubstituted 2,6,7-trimethyl-1,5-dioxo-1,2,5,6-tetrahydropyrido[3,4-d]pyridazines.

Synthesis of 4-aminosubstituted 2,6,7-trimethyl-1,5-dioxo-1,2,5,6-tetrahydropyrido[3,4-d]pyridazin es 2-11 and the results of the preliminary pharmacological screening of the selected compounds 2, 4, 5, 10, 11 are described in this paper.

Transformation of some pyrido[2,3-d]pyrimidine derivatives into other di- and triheterocyclic systems.

It was stated that three analogous ethyl 2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-5-carboxylates (7-9) react with hydrazine hydrate giving derivatives of the new heterocyclic system pyrido[2,3,4-ef]pyridazino[3,4-e]-1,2,4-triazepine (10-12), pyrido[3,4-d]pyridazine (16-18) and pentaazaphenalene (13-15). The latters were formed in low yields. The results of the preliminary pharmacological study of 2 of these compounds are reported.

Investigations on the synthesis and properties of some N-[4-phenyl(2-pyrimidinyl)-1-piperazinyl]alkyl (hydroxyalkyl)-3,4-pyridinedicarboximides.

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.

Synthesis and pharmacological evaluation of N-aryl(pyrimidinyl) piperazinylalkyl (hydroxyalkyl) derivatives of 1,2,3,4-tetra- and 1,2,3,4,5,6-hexahydropyrido[3,4-d]pyridazines.

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.

Synthesis, chemical and pharmacological properties of some 2,4-dioxo-1,2,3,4,5,6,7,8-octahydropyrimido [4,5-d]pyrimidines.

Synthesis of 6-substituted 2,4-dioxo-1,2,3,4,5,6,7,8-octahydropyrimido[4,5-d]pyrimidines [III-VI] obtained by cyclocondensation of 1-phenyl-6-aminouracil with formaline and the primary amines is described. Compounds III, V, VI in the Mannich reaction with secondary cyclic amines yield the corresponding 3-substituted N-aminomethyl derivatives VII-X. Some of them were active pharmacologically.

Synthesis, chemical and pharmacological properties of some N-aminoalkyl derivatives of 3,4-pyridinedicarboxamides.

The synthesis and properties of some N-aminoalkyl derivatives of 3,4-pyridinedicarboxamides (1-15) are reported. Imide 11, containing 2-hydroxy-3-(4-phenyl-l-piperazinyl) propyl substituent at the nitrogen atom, proved to have the lowest toxicity and, at very high dosages, to be the most pharmacologically active.

Investigations on the synthesis and properties of some N-arylpiperazinylalkyl 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.

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.

Investigations on the synthesis and properties of N-aryl (heteroaryl) piperazinylalkyl derivatives of imide of 6-methyl-2-(1-piperidino)-3,4-pyridinedicarboxylic acid.

The synthesis of N-aryl(heteroaryl)piperazinylalkyl derivatives of imide of 2-(1-piperidino)-3,4-pyridinedicarboxylic acid is reported. 3 examined compounds proved to be active pharmacologically in some tests.

Synthesis and properties of 1-aryl(pyrimidinyl)-piperazinylalkyl derivatives of ethyl 3-phenyl-7-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d] pyrimidine-5-carboxylate.

Synthesis of N-aryl (pyrimidinyl)piperazinylalkyl derivatives of ethyl 2,4-dioxo-1,2,3-4-tetrahydropyrido[2,3-d]pyrimidine-5-carboxylate is reported. Some of the obtained compounds are pharmacologically active.

Investigations on the synthesis and properties of some N-heteroarylpiperazinylalkyl derivatives of imides of 3,4-pyridinedicarboxylic acids.

The synthesis of N-heteroarylpiperazinylalkyl derivatives of imides of 3,4-pyridinedicarboxylic acids is described. In pharmacological screening some of the obtained compounds proved to be pharmacologically active.

Investigations on the synthesis and properties of arylpiperazinylalkyl derivatives of some dihydro- and tetrahydropyrido[2,3-d]pyrimidines.

Synthesis of S- and N-arylpiperazinylalkyl derivatives of ethyl 2-thio-4-oxo-3,4-dihydro- and 2,4-dioxo-1,2,3,4-tetrahydropyrido [2,3-d] pyrimidine-5-carboxylate is described. Some of the obtained compounds are pharmacologically active.

Investigations on the synthesis and properties of some N-arylpiperazinylalkyl derivatives of imides of 3,4-pyridinedicarboxylic acids.

The synthesis of N-arylpiperazinylalkyl derivatives of imides of 3,4-pyridinedicarboxylic acid is described. In pharmacological screening some of the obtained compounds displayed biological activity, but they were inactive as anxiolytic agents.

[Evaluation of the synthesis and action of O- and N-aryl-piperazine propyl derivatives of ethyl ester acid 3-cyano-2-hydroxy-6-methylpyridine-4-carboxyl]. / Badania nad synteza i wlasciwosciami O-i N-arylopiperazyny-lopropylowych pochodnych estru etylowego kwasu 3-cyja-no-2-hydroksy-6-metylopirydyno-4-karboksylowego.

It was stated that alkylation of the sodium salt of ethyl 3-cyano-2-hydroxy-6-methylpyridine-4-carboxylate by arylpiperazynylpropyl chlorides gives the mixture of the corresponding O- and N-isomers. The compound 1 showed analgesic and anxiolytic activity.

Synthesis and properties of new derivatives of ethyl 7-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrido [2,3-d]pyrimidine-5-carboxylate.

Condensation of diethyl 2-amino-6-methylpyridine-3,4-dicarboxylate with phenyl or cyclohexyl isocyanates gave the corresponding derivatives of ethyl 7-methyl-2,4-dioxo-1,2,3,4-tetrahydropyrido [2,3-d]pyrimidine- 5-carboxylate[(V), (VI)]. Alkylation of (V) and (VI) afforded the corresponding N-1 substituted derivatives (XI-XIX).