Synthesis and pharmacological properties of derivatives of alpha-amino-beta-(p-chlorobenzoyl)-propionic acid and alpha-amino-gamma-(p-chlorophenyl)-tetrahydrofuran-2-one.

Several new alpha-aminoderivatives of gamma-(p-chlorophenyl)-tetrahydrofuran-2-one were synthesized. alpha-Aminoderivatives of beta-(p-chlorobenzoyl)-propionic acid 2-13 were used as the substrates. After the reduction with NaBH4 at 10-12 degrees C and cyclization the compounds were converted into the appropriate derivatives of tetrahydrofuran-2-one 16-26.

Synthesis of alpha-aminomethyl derivatives of beta-phenyltetrahydrofuran-2-one.

beta-Phenyltetrahydrofuran-2-one-alpha-carboxylic acid 1 was transformed in the Mannich reaction into alpha-aminomethyl derivatives of beta-phenyltetrahydrofuran-2-one 2-6. The obtained alpha-aminomethyllactones, in reaction of ammono- and hydrazinolysis yield alpha-aminomethyl-beta-phenyl gamma-hydroxybutyric acid derivatives 7-12. Compounds 4, 5, 8, 9, and 10 depress the central nervous system, and compound 12 shows analgesic properties.

New 2-substituted derivatives of 5-aminomethyl-6-/p-chlorophenyl/-4,5-dihydro-2H-pyridazin-3-one.

Several new 2-substituted derivatives of 5-aminomethyl-6-/p-chlorophenyl/-4,5-dihydro-2H-pyridazin-3-one were synthesized. The derivatives of 5-aminomethyl-6-/p-chlorophenyl/-4,5-dihydro-2H-pyridazin-3-one (1-4) were used as the substrates. These compounds were converted by the reactions of cyanoethylation, hydroxymethylation and aminomethylation into appropriate 2-substituted derivatives of 5-aminomethyl-6-/p-chlorophenyl/-4,5-dihydro-2H-pyridazin-3-one (5-28).

Investigations on derivatives of 5-aminomethyl-6-/p-chloro-phenyl/-4, 5-dihydro-2H-pyridazin-3-one.

Several new derivatives of 5-aminomethyl-6-/p-chlorophenyl/-4, 5-dihydro-2H-pyridazin-3-one have been obtained. The substrates, beta-aminomethyl-beta-/p-chlorobenzoyl/-propionic acid derivatives 1-5, were converted by reactions with hydrazine hydrate or monosubstituted hydrazines, i.e.

Investigations on the synthesis and properties of new derivatives of methyl 3H-2-imino-7-methyl-4-oxopyrido [3,2-e]-1,3-thiazine-5-carboxylate.

Condensation of dimethyl 2-chloro-6-methylpyridine-3,4-dicarboxylate with thiourea and its N-substituted derivatives is described. It has been found that depending on the kind of substituents in the starting thiourea derivatives, pyrido [3,2-e]-1,3-thiazine or pyrido [2,3-d] pyrimidine derivatives were formed.

Synthesis of derivatives of beta-aminomethyl-gamma-(p-chlorophenyl)-gamma-hydroxybutyric acid.

Several new derivatives of beta-aminomethyl-gamma-(p-chlorophenyl)-gamma-hydroxybutyric acids have been obtained. The substrates, beta-aminomethyl derivatives of gamma-(p-chlorophenyl)-tetrahydrofuranone-2 1-4, were converted by the reactions of ammonolysis, aminolysis and hydrazinolysis into appropriate amides and hydrazides of beta-aminomethyl-gamma-(p-chlorophenyl)-gamma-hydroxybutyric acid. Compounds 10, 11, 16, 18, 19 and 20 show depressant activity on CNS, while compounds 6 and 8 demonstrate antiinflammatory action.

Synthesis of D,L beta-aminomethyl derivatives of gamma-(p-chlorophenyl)-tetrahydrofuran-2-one.

Several new D,L beta-aminomethyl derivatives of gamma-(p-chlorophenyl)-tetrahydrofuran-2-one have been synthesized. The derivatives of D,L beta-aminomethyl-beta-(p-chlorobenzoyl)-propionic acid 2-6 were used as the substrates. These compounds were obtained by the Mannich reaction from acid 1, cyclic secondary amines and formaldehyde.

Studies on derivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid. VI. Syntheses and properties of 2-N-aralkyl-alpha-sulphoderivatives of tert-amides of 2-amino-4-p-chlorophenylthiazole-5-acetic acid.

In the course of the studies on compounds with expected antiinflammatory and immunosuppressive activity several new tert-amides derivatives of 2-N-aralkylamino-alpha-sulpho-2-amino-4-p-chlorophenylthiazole-5-acetic acid were synthesized. Some of the previously described Schiff bases reacted with aqueous alcoholic solution of sodium bisulphite and as a result several (III-VIII) alpha-sulphoderivatives were obtained. The course of the reactions was studied and the structure of the new compounds was confirmed.

Studies on derivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid. V. Syntheses of 2-N-aralkylidene and 2-N-aralkyl derivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid.

A number of new N-aralkylidene and N-aralkyl derivatives of amides and hydrazides of 2-amino-4-p-chlorophenylthiazole-5-acetic acid (III-XXIX) have been synthesized. These compounds were obtained in two various ways depending on the character of substituents in the carboxyl group. The chemical structure of the newly obtained compounds was determined on the basis of the data of elementary and spectral analyses.

Studies on derivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid. IV. Addition reactions of thioglycolic acid to 2-N-aralkylidene derivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid.

In the course of studies on compounds with expected antiinflammatory and immunosuppressive activity a series of new derivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid have been synthesized. Several new and unexpected details of the chemical properties of these compounds were revealed. The chemical structure of the new compounds was confirmed by degradation and identification of the decomposition products and by spectral analysis.

Syntheses and pharmacological analysis of new derivatives of tetrahydro-[1,3]-thiazine and 2-thiobarbituric acid.

Three groups of compounds:1,3-thiazine derivatives, 2-thiobarbituric acid derivatives and noncyclic thioureide were obtained as a result of condensation of some N, N1-derivatives of thiocarbamide and malonyl dichlorides, depending on the reaction conditions and chemical character of reagents. It was observed that the substituents beside nitrogen atoms of thiocarbamides, the kind of acid chloride and reaction conditions influenced the course of reaction. The structure of the newly synthesized compounds was proved by the analysis of PMR spectrum and the interpretation of IR spectrum.

Studies on the derivatives of thiazole acetic acid. II. Syntheses and pharmacological analysis of 2-N-aralkylidene and 2-N-aralkyl derivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid.

A number of 2-N-aralkylidene, 2-N-aralkyl and 2-N-aralkyl-alpha-sulphoderivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid (I, R = H) and its methyl ester (I, R = CH3) were synthesized. As a result of condensation of methyl ester I with various aromatic aldehydes in boiling benzene solution, the Schiff-bases (anils) II--VIII were obtained. After reduction with NaBH4 compounds II--VIII were transformed into adequate amino esters IX--XV.

Studies on the derivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid. I. Syntheses and pharmacological analysis of acylderivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid.

A number of new acyl and imidoderivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid (II) and its methyl ester (VII) were synthesized. Methyl ester VII heated in benzene solution with acid anhydrides was transformed into adequate acyl derivatives (VIII, IX, X, XIII, XVI). Some of them (X, XIII, XVII) by heating with acetic anhydride underwent cyclization and were transformed into the imido derivatives (XI, XIV, XVIII).

Hexahydrochromane derivatives. Part I.

Several new 4-substituted derivatives of hexahydrochromane were obtained. A new method for preparing the key intermediate for synthesis of this compounds i.e.

Studies on derivatives of tetrahydro [1,3]-thiazine.

In the course of studies on compounds with expected antiinflammatory and immunosuppressive activity a series of new derivatives of tetrahydro [1,3]-thiazine-4-one-6-carboxylic acid, tetrahydro [1,3]-thiazine-4,6-dione and 2-thiobarbituric acid have been synthetized. Several new and unexpected details of the chemical behavior of these compounds were revealed. The chemical structure of the new compounds was confirmed by degradation and identification of the decomposition products and spectral analysis.

Synthesis of derivatives of 2-amino-4-p-chlorophenylthiazole-5-acetic acid.

In the course of studies on compounds with expected antiinflammatory and immunosuppressive action a number of new derivatives of 2-amino-4-p-chlorophenylthiazole-s-acetic acid have been synthetized. The chemical structure of these compounds has been confirmed by elemental analysis and IR spectra. The newly obtained compounds were investigated pharmacologically.

Studies on derivatives of phenyltetrahydrofuranone-2-carboxylic acids. VI. Derivatives of beta-phenyltetrahydrofuranone-2-beta-carboxylic acid.

Proceeding with the studies on derivatives of pheyl-tetrahydrofuranone-2-carboxylic acids the authors have stated that the reaction of hydroxymethylation of ethyl ester of beta-phenyl-beta-cyanopropionic acid I gives transitionally beta-phenyl-beta-cyano-beta-hydroxymethylpropionic acid II which, after a long time, transforms into an amide of beta-phenyl-tetrahydrofuranone-2-beta-carboxylic acid (III). Amide III is tranformed, through acid IV, into acid chloride V that gives a number of derivatives: amide III, substituted amides (VI-IX), methyl ester X, ureide XI, and aminomethylamides (XII, XIII). The chemical structure of these compounds has been confirmed by elemental analysis and IR and PMR spectra.

Derivatives of 3-p-chlorophenyl-3-oxopropane and 3-p-chlorophenyl-3-hydroxypropane-1-carboxylic acids.

Starting from gamma-chlorophenyltetrahydro- and gamma-chlorophenyldihydro-furan-2-ones (2 and 12), some new amides and hydrazides of the acids mentioned in the title were prepared (Table 1 and 2). Of the obtained compounds the following 10, 14, 15, 17, 20--23 show central depressant action.