The reaction of 3-ethoxycarbonylcoumarin with derivatives of cyanoacetylhydrazine directly in the sample tube of the NMR spectrometer was investigated by 1H NMR spectroscopy. The structure of the components of the reaction mixtures was established, and their relative concentrations at the various stages of the reaction were estimated. The sequence of processes occurring in the reactions was analyzed. Both the general characteristics and the differences in the course of the reaction with cyanoacetylhydrazine or its N-isopropylidene derivative as second component were established.

The mono- and diimine products from the condensation of 3-formyl-4-hydroxycoumarin and various diamines were synthesized. It was shown by 1H NMR and mass spectrometry that the obtained compounds in DMSO-d6 solution and in gas phase exist in the E- and Z-keto-enamine forms.

Acylation of 1-ethyl-3-(N,N-dimethyl)aminomethylene-1,2-dihydro-2-indolinone by succinic anhydride in the presence of aluminum chloride has been studied. PMR spectroscopy shows that this acylation leads to formation of a mixture of the 5- and 6-succinoyl derivatives with predominance of the latter (cis and trans isomers of both these products were found). The reaction of the latter with hydrazine hydrate gives hydrazinomethylene derivative of 2-indolinone, in reaction of which with various carbonyl compounds a series of oxindol hydrazones has been obtained. The reaction of these products with primary amines smoothly leads to transamination and the formation of enamines of 1,6-disubstituted 2-indolinone.

Condensation of indolin-2-one (oxindole) lactim ether with malononitrile leads to 2-dicyanomethylidene-2,3-dihydroindole, the reaction of which with dimethylformamide diethyl acetal (or with triethyl orthoformate) and the subsequent cyclization afford 4-cyanopyrido[4,3- b]indoles (γ-carbolines). 3-Amino-4-cyanopyrido[4,3-b]indole was used in the synthesis of substituted pyrimido[4,5-c]-γ-carbolines.

We have synthesized a series of 1,3-dimethyl-6-(5'-aminopyrimidyl-6-thio)uracyl derivatives, studied their conversions, and characterized some of their properties.

Derivatives of 1,3-dimethyl-6-(5′-aminopyrimidylthio-6′)uracils were synthesized and some of their properties and reactions were studied.

Research on the analysis and standardization of the new drug led to the development of an analytical procedure for noopept in the parent substance and the drug form, tablets [2]. However, further research showed that the development procedures had several drawbacks. Thus, the developed method for quantitative determination of noopept parent substance, a reverse titration method using preliminary hydrolysis, is irreproducible and inaccurate. Furthermore, it was demonstrated that the developed TLC procedure for determining impurities in noopept is not sensitive enough [3]. Therefore, the need arose to develop new, more sensitive, accurate, and reproducible procedures for qualitative and quantitative analysis of the drug. This problem was solved by selecting physicochemical analytical methods. Structural features of noopept enable physicochemical methods based on UV absorption of the drug such as UV spectrophotometry and high-performance liquid chromatography (HPLC) with spectrophotometric detection to be used to analyze its quality. The main goal of our research was to study the physicochemical properties and develop an analytical procedure of noopept parent substance to create a state reference sample (I).

The physicochemical properties of noopept, a new original drug with nootropic action, have been studied with a view to developing analytical methods, establishing quality criteria for the parent drug substance, and creating the state reference sample (SRS). These methods will be included in the project of normative documentation on the SRS of noopept.

Condensation of lactim ethers of 3,4-dihydrocarbostyril and 1H-2,3,4,5-tetrahydrobenz[b]azepin-2-one with malonodinitrile, cyanoacetamide, and ethyl cyanoacetate gave the corresponding 2-methylidene derivatives. Their reactions with dimethylformamide diethyl acetal followed by cyclization into benzo[b][1,6]naphthyridines and pyrido[4,3-b]benz[f ]azepines were studied.

The physicochemical properties of noopept, a new domestic original drug with nootropic action, have been studied with a view to developing analytical methods, establishing quality criteria for the parent drug substance, and creating the state reference sample (SRS). These methods will be included in a draft of the regulation on the SRS of noopept.

The chemical composition of the juice of freshly collected great burdock (Arctium Lappa L.) leaves was studied. The main components in the ethyl acetate extract were determined. Adifference between the samples collected in two successive years was found.

Reaction between the N,N′-diisopropylidene and N,N′-diacetyl derivatives of malonic acid dihydrazide and 3-acyl(3-cyano, 3-ethoxycarbonyl)coumarins under the conditions of the Michael reaction lead to the formation of N′-isopropylidene and N′-acetyl derivatives of coumarin-3-carboxylic acid hydrazide. Ethoxycarbonylacethydrazide reacts in an analogous manner. Special features have been studied of the interaction of malonic acid amide derivatives with unsubstituted coumarin and with coumarins containing electron-withdrawing groupings in position 3 of the ring.

The chemical composition of an extract from freshly collected Arctium lappa leaves was studied. The main components in ethyl acetate extract were determined. A difference between the samples collected in two successive years was established.

The new modification of accq-tag-HPLC method for the rapid analysis of L-proline and GABA in culture medium is presented. We have shown the influence of the concentration of L-isoleucine added to cultere medium on GABA accumulation. Accumulation of γ-aminobutiric acid (GABA) in the culture broth of E. coli strains is proved using mass-spectroscopy and NMR methods.

We have studied some properties and conversions of pyrimido[4,5-b]-1,4-benzothiazepines: reduction, oxidation, reactions with nucleophilic reagents (methanol, hydrazine, hydroxylamine, o-methylhydroxylamine, and thiosemicarbazide). We have synthesized derivatives of a novel heterocyclic system: pyrimido[5,4-c]isoquinoline.

By reaction of 4-substituted 5-amino-6-mercaptopyrimidines with 5-bromo-2,2-dimethyl-4,6-dioxo-1,3-dioxane, we have obtained 4′-substituted 5-(5-amino-6-pyrimidylthio)-2,2-dimethyl-4,6-dioxo-1,3-dioxanes. We have studied diazotization of these compounds by isoamyl nitrite. In the case of 4′-methoxy- and 4′-dimethylamino-substituted derivatives, we have obtained derivatives of novel heterocyclic systems: pyrimido[5,4-e][1,3,4]thiadiazine and pyrimido[5,4-e][1,3,4]thiadiazine-7-spiro-5′-1,3-dioxane, and in the case of the 4′-isopropylamino-substituted derivative we obtained 4-isopropyl-7-(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)-1,2,3-triazolo[5,4-d]pyrimidin-7-ylidene.

A new modification of the accq-tag-HPLC technique for the rapid determination of L-proline and γ-aminobutyric acid (GABA) in a culture medium is proposed. The concentration of L-isoleucine added to the culture medium is shown to influence the accumulation of GABA. The accumulation of GABA in the culture media of E. coli strains is confirmed by the data of mass spectroscopy and NMR.