Influence of additives and storage temperature on physicochemical and microbiological properties of eye drops containing ceftazidime.

The purpose of the studies was to examine the influence of additives and the storage temperature on the physicochemical properties of the eye drops containing ceftazidime and on the antimicrobial activity of ceftazidime in the eye drops stored for 30 days at the temperature of 4 degrees C and 2 degrees C. The eye drops were 1% sterile aqueous solutions of Biotum (Ceftazidimum) in citrate buffer of pH 6.18-6.

Physicochemical and microbiological properties of eye drops containing cefuroxime.

The purpose of the studies was to examine the influence of the additives and storage temperature on physicochemical properties and on the antimicrobial activity of cefuroxime in the eye drops. The eye drops were 1% sterile aqueous solutions of cefuroxime in citrate buffer of pH 6.15-6.

Influence of additives and storage temperature on physicochemical and microbiological properties of eye drops containing cefazolin.

The purpose of the studies was to choose additives for eye drops containing cefazolin and the assessment of the influence of used additives and the storage temperature on the physicochemical properties and the stability of the eye drops. The drops were 1% sterile solutions of cefazolin in citrate buffer of pH 6.15-6.

Synthesis and properties of 4-substituted-1-piperazinyl-propyl derivatives of 1-phenyl-7-methylpyrimido-[4,5-d]pyrimidin-4-one.

In reactions of 1-phenyl-7-methyl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimido[ 4,5-d]pyrimidin e (1) with 1-(3-chloropropyl)-4-methyl(phenyl, 3-chlorophenyl, 2-pyrimidynyl, 2-thiazolyl)piperazines (5), mixtures of isomeric N- and S-substituted derivatives of compound 1 (3 and 4) were obtained. Isomers were separated by fractional crystallization. The structure of novel compounds 3 and 4 was confirmed by elemental and spectral analyses.

Synthesis and properties of the derivatives of 2-alkylthio-4-oxo-3,4- (and -1,4)-dihydropyrido-[2,3-d]pyrimidine-5- and -6-carboxylic acids.

Condensation of diethyl 2-amino-6-methylpyridine-3,4-dicarboxylate (I) with the corresponding isothiocyanates afforded derivatives of ethyl 4-oxo-2-thioxo-1,2,3,4-tetrahydropyrido [2,3-d]pyrimidine-5-carboxylate (V-VII). Alkylation of (V), (VI) and (XI) gave the corresponding derivatives of ethyl 2-alkylthio-4-oxo-3,4-(and 1,4)-dihydropyrido[2,3-d]pyrimidine-5- and -6- carboxylate [(XII-XVI), (XX-XXII)]. Some of the obtained compounds were active pharmacologically.

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).

Syntheses and properties of selected derivatives of pyrimido[5,4-e]-1,3-thiazine and pyrimido[4,5-d]pyrimidine.

In the reactions of ethyl 4-chloro/tosyloxy/-2-methylpyrimidine-5-carboxylate with differently substituted thioureas, new derivatives of 2,3-dihydro-7-methylpyrimido-[5,4-e]-1,3-thiazine (5-9) and of 7-methyl-1,2,3,4-tetrahydropyrimido[4,5-d]pyrimidine (12, 13) were obtained. Besides, some derivatives of 4-phenylamino-2-methylpyrimidine-5-carboxylic acid (15-20) were also synthesized. Structure of the compounds was confirmed by spectral analysis (IR, H-NMR) and chemical transformations.

Synthesis and properties of new 3-acyl- and 3-carbamoyl derivatives of esters of 3H-2-imino-7-methyl-4-oxopyrido[3,2-e]-1,3-thiazine-5- and -6-carboxylic acids.

It was stated that esters of 3H-2-imino-7-methyl-4-oxopyrido[3,2-e]-1,3-thiazine-5- and -6-carboxylic acids react with acyl anhydrides and chlorides giving 3-acyl derivatives. Reaction of the above mentioned esters with isocyanates affords the corresponding 3-carbamoyl derivatives.

Synthesis and properties of amides of 1-benzyl-3-methyl- and 1-butyl-3-phenyl-7-methyl-4-oxo-2-thioxo (2,4-dioxo)-1,2,3,4-tetrahydropyrido-[2,3-d]pyrimidine-6-carboxy lic acids.

Amides of 1-benzyl-3,7-dimethyl-4-oxo-2-thioxo-1,2,3,4- tetrahydropyrido[2,3]pyrimidine-6-carboxylic acid were obtained by the condensation of ammonia, primary and secondary cyclic amines with the corresponding acid chloride. As by - products amides of 1-benzyl-3,7-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyr imidine-6- carboxylic acid were isolated as a result of desulfuration. The same reaction performed with chloride of 1-butyl-7-methyl-3-phenyl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyri do[2,3- d]pyrimidine-6-carboxylic acid gave mainly the corresponding 2,4-dioxo-amides.

A novel system: 2H-pyrido[3,2-e]-1,2-thiazine-1,1-dioxide. Synthesis and properties of some derivatives.

A rearrangement of 2H-2-acetonyl(phenacyl)-4,6-dimethyl- pyrido[3,2-d]isothiazoline-3-one-1,1-dioxides (I), (II) to derivatives of the unknown system of 2H-pyrido[3,2-e]-1,2-thiazine-1,1-dioxide (V), (XIII) is described; the synthesis of 2-N-substituted derivatives (VI - XII), (XIV - XVI) is also given. The structures of the new compounds were confirmed with elemental analyses and spectral data (I.R.

Synthesis and properties of some derivatives of 2H-4,6-dimethylpyrido[3,2-d]isothiazolin-3-one-1,1-dioxide.

The synthesis of 2H-4,6-dimethylpyrido[3,2-d]isothiazolin-3-one-1,1-dioxide and its 2-N-substituted derivatives are described. Structures of the obtained compounds were determined on the basis of elemental analyses and spectral data I.R.

Investigations on the synthesis and properties of new derivatives of pyrido[3,2-e]-1,3-thiazino[3,2-a]-s-triazine.

It has been found that the condensation of esters of 3H-2-imino-7-methyl-4-oxopyrido[3,2-e]-1,3-thiazine-5- and -6-carboxylic acids (I, II) with formaldehyde and primary amines affords the corresponding derivatives of a new heterocyclic system pyrido[3,2-e]-1,3-thiazino [3,2-a]-s-triazine (IX-XXIV).

Synthesis and properties of 3-aminomethyl derivatives of 3H-2-imino-7-methyl-4-oxopyrido-[3,2-e]-1,3-thiazine-5- and -6-carboxylic acids.

It was stated that esters of 3H-2-imino-7-methyl-4-oxopyrido [3,2-e]-1,3-thiazine-5- and -6-carboxylic acids (I, II) undergo the Mannich reaction giving the corresponding 3-aminomethyl derivatives (III-XIV). Derivatives of ester II [(XII) and (XIV)] showed distinct analgesic and antiserotonic activities.

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.

Investigations on the synthesis and properties of new derivatives of ethyl 3H-2-imino-7-methyl-4-oxopyrido [3,2-e]-1,3-thiazine-6-carboxylate and isomeric compounds.

Condensation of diethyl 2-chloro-6-methylpyridine-3,5-dicarboxylate (IV) with thiourea and alkyl or alkenyl N-mono- and N,N'-disubstituted thioureas gives mainly the corresponding derivatives of ethyl 3H-2-imino-7-methyl-4-oxopyrido [3,2-e]-1,3-thiazine-6-carboxylate (VI-XII). As by-products isomeric derivatives of ethyl 7-methyl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrido [2,3-d) pyrimidine-6-carboxylate (XIII-XVIII) are 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.