Anticonvulsant activity and succinate dehydrogenase inhibitory property of new substituted thiobarbiturates

Eight 1-aryl-3-(2-pyridyl)thiobarbiturates were synthesized and evaluated for their anticonvulsant property and their ability to inhibit succinate dehydrogenase activity of rat brain homogenates. These substituted thiobarbiturates (100 mg./kg., i.p.) provided 20–60% protection against pentylenetetrazol-induced convulsions in albino mice. Low toxicity of these compounds was reflected by their high approximate LD₅₀ values which were found to range from 500–1000 mg./kg. All substituted thiobarbiturates (ImM) inhibited in vitro succinate dehydrogenase activity and the degree of inhibition ranged from 10–72%.     

Mass spectrometric fragmentation of S-(1-aryltetrazol-5-yl)-monothiocarbonic acid esters

The mass spectra of S-(1-aryltetrazol-5-yl)-monothiocarbonic acid esters have been studied. The stability of the ester molecular ions is lower than the stability of the corresponding 1-aryl-5-mercaptotetrazoles. Substituents at the phenyl group increase the stability, whereas the influence of the ester alkyl groups is very small. The esters undergo fragmentation via four different fragmentation pathways. The elimination of carbon dioxide is influenced by an ‘ortho effect’ of the substituents.     

Synthesis and properties of substituted 2-thioxohexahydropyrimidine-5-carbohydrazides

A regioselective method for the synthesis of substituted (4R*,5S*,6R*)-2-thioxohexahydro-pyrimidine-5-carbohydrazides from the corresponding diastereomers of hexahydro-2H-chromeno[4,3-d]pyrimidines was developed. In acidic medium, the obtained hydrazides are prone to retro reaction to give hexahydro-2H-chromeno[4,3-d]pyrimidines.

     

Synthesis of substituted 5-diethoxymethyl-5-ethyloxazolidines

Mixtures of stereoisomeric 2-diethoxymethyl-5-ethyloxazolidines with one of the stereoisomeric forms predominating were obtained by the reaction of 2-ethyl-2-formyloxirane diethyl acetal with alkyl-substituted Schiff bases in ethanol solution.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, 985–988, July, 1987.     

Aminomethylation of substituted 5-hydroxypyrimidines

Conditions that make it possible to obtain aminomethyl derivatives of 2-R-4,6-dimethyl-5-hydroxypyrimidine that are substituted both in the pyrimidine ring (R = H) and at the methyl group of the side chain (R = H, CH₃, C₆H₃) were found. The facts established in this research make it possible to propose various substitution mechanisms.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 681–683, May, 1980.     

Synthesis of substituted cyclopentanones from 6-methylhept-5-en-2-one

Readily available tert-butyl- and phenyl sulfoxide derivatives of methylheptenone were converted by the Pummerer method to the corresponding five-membered keto sulfides which are probable precursors of iridanes and related terpent cyclopentanoids.Translated from Izvestiya Akademii Nauk SSSR, No. 7, pp. 1569–1574, July, 1991.     

Syntheses of substituted 2-(1-methyl-5-nitro-2-benzimidazolyl)quinolines

Reaction of N-methyl-2-amino-4-nitroaniline ( 1 ) with lactic acid afforded 2-(1-hydroxyethyl)-1-methyl-5-nitrobenzimidazole ( 2 ). Oxidation of compound 2 with chromic acid in acetic acid gave 2-acetyl-1-methyl-5-nitrobenzimidazole ( 3 ). Reaction of compound 3 with substituted 2-aminobenzaldehyde ( 4 ) under basic conditions yielded substituted 2-(1-methyl-5-nitro-2-benzimidazolyl)quinolines ( 5 ). Condensation and cyclization of o-aminoacetophenone (or substituted o-aminobenzophenones) with compound 3 under acetic condition afforded compound 7 . Condensation and cyclization of compound 1 with indole-3-carboxaldehyde ( 11 ) in ethanol in the presence of excess nitrobenzene gave 3-(1-methyl-5-nitro-2-benzimidazolyl)indole ( 12 ).     

Nitration products of substituted 1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-ones

Highly substituted, novel, 1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-ones were obtained by direct nitration of the corresponding mono- or di-substituted 5-phenyl-1,4-benzodiazepines. Substituent effects and the orientation of aromatic substituents in the nitration products are discussed. The single-crystal X-ray structural data for one of these products, 18 , is given.     

Synthesis of functionally substituted 5-phenylthiazoles

The reaction of esters and amides of 3-phenyl-3-chloro-2-oxopropionic acid with thioamides and thiourea gave new 5-phenylthiazoles.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12, pp. 2854–2856. December, 1990.     

Anticonvulsant activity of 3-oxo-5-substituted benzylidene-6-methyl-(4H)-2-pyridazinylacetamides and 2-pyridazinylacetylhydrazides

A series of 3-oxo-5-substituted-benzylidene-6-methyl-(4H)-2- pyridazinylacetamides and 2-pyridazinylacetylhydrazides were synthesized and evaluated for anticonvulsant activity against electrically and chemically induced seizures. In the maximal electroshock-induced seizures test, most of the derivatives showed an anticonvulsant effect better than that of sodium valproate, a commonly used anticonvulsant drug. At 100 mg/kg orally, compounds 5a and 5b respectively protected 50 and 60% of the mice against pentylentetrazole-induced seizures. In addition, these two derivatives showed significant anticonvulsant properties at doses that did not produce ataxia or sedation. The title compounds were also tested for their ability to antagonize convulsions induced by bicuculline and strychnine. Their effect on tremors induced by oxotremorine in mice was also evaluated.     

Structure/property correlation of substituted compounds based on graph theory

The molecular graph of compounds containing heteroatoms is expressed by introducing a new parameter β into the adjacency matrix at the position of the carbon-heteroatom pairs. The Wiener equation is modified to correlate some physical properties (normal boiling points, critical constants and refractive index) of acyclic halogen derivatives, ethers, amines and alcohols with the graph invariants (modified Wiener number, 3-path number and 2-path number). The calculation yields successful results except for alcohols.     

Synthesis of 5-aryl-2-oxopyrrole derivatives as synthons for highly substituted pyrroles

A small library of 2-oxo-5-(hetero)arylpyrroles was prepared starting from 2,3-dioxo-5-(hetero)arylpyrrolidines. The large synthetic possibilities of these 2-oxopyrroles were investigated. The 2-oxopyrroles offer a large number of possible derivatizations including reactions with electrophiles. The chloroformylation of 2-oxo-5-(hetero)arylpyrroles provides pyrrole carbaldehydes. Some pyrrole carbaldehydes were used to synthesize polycyclic compounds like pyrrolo[3,4-d]pyridazinones, a thienopyrrole, a pyrrolobenz[1,4]oxazepine, a pyrrolobenzo[1,4]thiazepine, and a pyrrolobenzo[1,4]diazepine. Hereby we showed through a short exploration that the oxopyrroles and analogues are interesting and versatile synthetic building blocks.     

Stereochemical studies of 5-methyl-3-(substituted phenyl)-5-[(substituted phenyl) hydroxy methyl]-2-thiooxazolidin-4-ones

The synthesis and stereochemical aspects of the aldol products, 5-methyl-3-(substituted phenyl)-5-[(substituted phenyl) hydroxy methyl]-2-thiooxazolidin-4-ones, are discussed.     

5-芳基-1,3,4-噻二唑-2-胺衍生物的合成

在冰醋酸催化下,芳香醛(2a～2g)分别和氨基硫脲(3)反应合成得到芳亚胺基硫脲衍生物(4a～4g),中间体4无需经柱层析纯化,然后在三氯化铁作用下反应关环,得到7个目标化合物5-芳基-1,3,4-噻二唑-2-胺(1a～1g).产物结构经1 H NMR、13 C NMR和ESI-MS确证.然后分别以中间体(E)-2-苄...     

Synthesis and some properties of substituted, 4, 5-cyclopentano-Δ2-isoxazolines

The 1, 3-dipolar cycloaddition of acetonitrile oxide and ethyl cyanoformate oxide to cyclopentenone and the structure and some of the properties of the resulting ²-isoxazolines were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 625–628, May, 1976.     

Voltammetric studies on some substituted 5-arylidene-2-thiohydantoin in non aqueous medium

Summary Differently substituted 5-arylidene-2-thiohydantoins (2a–f) were studied electrochemically in benzonitrile with 0.1M tetra-n-butylammonium-perchlorate as supporting electrolyte using DC-, cyclic voltammetry (CV), coulometry and controlled potential electrolysis (CPE). These compounds are oxidized in a one two-electron transfer process or in irreversible two successive one-electron processes to the corresponding diradical, which simaltaneously reacts with the solvent to regenerate the starting species. On the other hand the reduction products are the 5-arylidene-4-imidazolidinone-2-thiols.

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Voltammetrische Untersuchungen einiger substituierter 5-Aryliden-2-thiohydantoine in nichtwäßrigem Medium

Zusammenfassung Es wurden verschieden substituierte 5-Aryliden-2-thiohydantoine (2a–f) in Benzonitril mit 0.1M Tetra-n-butylammoniumperchlorat als Leitsalz elektrochemisch untersucht, wobei DC-, Cyclische Voltammetry (CV), Coulometrie und kontrollierte-Potential-Elektrolyse (CPE) eingesetzt wurden. Die Verbindungen wurden entweder in einem Zweielektronen-Transferprozeß oder in zwei irreversiblen Prozessen aufeinanderfolgender Einelektronen-Stufen zum entsprechenden Diradikal oxidiert, welches simultan mit dem Solvens unter Regenerierung der Startspezies reagiert. Andererseits sind die Reduktionsprodukte die 5-Aryliden-4-imidazolidinon-2-thiole.