Researches ok heterocyclic rings containing nitrogen and sulfur II. Orotylamino acids,their esters,and salts of orotic acid with amines

Esters of orotylamino acid are synthesized by reacting orotyl chloride with glycine andα- andβ-alanine esters. Orotylamino acids are prepared by reducing the benzyl ester of orotylglycine, or by reacting orotyl chloride with sodium salts of amino acids. A series of salts of orotic acid are prepared by reacting orotic acid with amines.     

Derivatives of condensed pyrimidine,pyrazine, and pyridine systems

Reaction of 2-mercapto-3-amino-5,6-dimethyl- and 2-mercapto-3-amino-5,6-diphenylpyrazines withα-halo acid esters gave 2-carbethoxy-3-aminopyrazines, which are converted by the action of sodium ethoxide to 5,6-dimethyl- and 5,6-diphenylpyrazino[2,3-b]-[1,4]thiazin-6-ones. The latter are more conveniently obtained from 2-chloro-3-amino-5,6-dimethyl- and 2-chloro-3-amino-5,6-diphenylpyrazines and thioglycolic acid. 5,6-Dihydropyrazinothiazine is formed by reduction of 5,6-dimethyl pyrazino[2,3-b][1,4]thiazin-6-one, whereas the 2,3-dimethyl-5-amino-6-sulfonic acid and its N-oxide are formed by oxidation.     

Microspheres based on poly(3-hydroxy)butyrate for prolonged drug release

The kinetics of the controlled release of the antiproliferative drug dipyridamole from microspheres based on the biocompatible and biodegradable polymer poly(3-hydroxy)butyrate is studied. As carriers for dipyridamole, microspheres prepared from a solution of poly(3-hydroxy)butyrate by single emulsion method are used. Under in vitro conditions, the kinetic curves describing the release of dipyridamole from microspheres with diameters of 19, 63, and 92 μm show two characteristic regions: the region of fast drug release within a short time period and a well-pronounced continuous linear region. For microspheres with a diameter of 4 μm, the linear region is missing. Analysis of the kinetic curves illustrating controlled drug release together with the measurements on polymer degradation shows that their kinetic profiles depend on the diffusion-controlled process and hydrolytic degradation of poly(3-hydroxy)butyrate. The diffusion kinetic equation describing both linear and nonlinear regions of dipyridamole released from the microspheres involves the sum of two terms: desorption from the sphere via the diffusion-controlled mechanism and drug release via the zero-order reaction. The linear region of the drug release curve is explained by the zero-order hydrolysis of poly(3-hydroxy)butyrate. The diffusion coefficients and kinetic constants are calculated. For bigger microspheres, the existence of the continuous linear region in the corresponding kinetic curves makes it possible to use microsystems based on poly(3-hydroxy)butyrate and dipyridamole as novel systems for local prolonged drug delivery.     

Synthesis and X-ray structural study of bis(2-sodiumsulfonylethyl) sulfoxide hexahydrate

The structure of bis(2-sodiumsulfonylethyl) sulfoxide hexahydrate (1), which was synthesized by the reaction of divinyl sulfoxide with sodium metabisulfite in an aqueous ethanol medium, has been determined by X-ray structural analysis. Both Na⁺ cations are coordinated by six O atoms of crystallization water molecules and SO₃ groups; the coordination sphere is a distorted octahedron. The crystals are stabilized by an extensive network of hydrogen bonds through the water molecules of crystallization.     

Researches ok heterocyclic rings containing nitrogen and sulfur II. Orotylamino acids, their esters, and salts of orotic acid with amines

Esters of orotylamino acid are synthesized by reacting orotyl chloride with glycine and- and-alanine esters. Orotylamino acids are prepared by reducing the benzyl ester of orotylglycine, or by reacting orotyl chloride with sodium salts of amino acids. A series of salts of orotic acid are prepared by reacting orotic acid with amines.For Part I see [8].     

Investigation of nitrogen- and sulfur-containing heterocyclic compounds

The halogenation of 2,3-dimethylpyrazino[2,3-b][1,4]thiazin-6-one with bromine or 1 mole of sulfuryl chloride gives 7-bromo-and 7-chloropyrazino[2,3-b][1,4]thiazin-6-ones, while 2 moles of sulfuryl chloride give 7,7-dichloropyrazino[2,3-b][1,4]thiazin-6-one. A number of 7-amino-and 7,7-diaminopyrazino[2,3-b][1,4]thiazin-6-ones were obtained by the reaction of the appropriate halo derivatives with amines. Some of the pyrazino[2,3-b][1,4]thiazin-6-one derivatives inhibit the growth of interweavable tumors in animals.See [3] for communication XX.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1498–1501, November, 1971.     

Investigation of nitrogen- and sulfur-containing heterocycles

The reaction of o-aminomercapto derivatives of pyrimidine, pyrazine, and pyridine, with -halo acid nitriles was investigated. The corresponding cyanoalkylthio heterocycles, which were converted to 6-amino derivatives of pyrimido[4,5-b]-, pyrazino[2,3-b]-, and pyrido-[2,3-b]-1,4-thiazines, were obtained. The structures of the substances obtained were confirmed by IR, UV, and PMR spectroscopy.See [10] for communication XXII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 944–948, July, 1972.     

Ring-chain tautomerism of S-acylalkylmercapto-substituted aminoquinoxalines

The ring-chain tautomerism of S-acylalkylmercapto-substituted aminoquinoxalines was studied by means of IR and PMR spectroscopy. It was established that, depending on the substituants,the investigated compounds have open or cyclic structures or exist in the form of mixtures of these forms. Mixtures of diastereomeric forms were detected for two of the investigated compounds.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 114–120, January, 1979.