4-Hydroxy-2-quinolones. 152*. 3-acetyl-4-hydroxy-2-oxo-1,2-dihydroquinoline and its biologically active derivatives

A synthesis and study of the spatial structure of 3-acetyl-4-hydroxy-2-oxo-1,2-dihydroquinoline have been carried. 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids [1-(4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)ethylidene]hydrazides were prepared from this compound by two routes. A comparative analysis of the antitubercular properties of the synthesized compounds and of the closely structurally related N,N′-di(1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carbonyl)hydrazines has been performed. *For Communication 151 see [1]. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 214–222, February, 2009.     

4-Hydroxy-2-quinolones 132. Synthesis, chemical, and biological properties of 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids 2-nitrobenzylidenehydrazides

1-R-4-Hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids 2-nitrobenzylidenehydrazides are reduced to the corresponding quinoline-3-carboxamides by zinc in glacial acetic acid but in refluxing triethylphosphite they are converted to the symmetrical N,N′-di(4-hydroxy-2-oxo-1,2-dihydro-3-quinolinoyl)hydrazines. A study of the antitubercular activity of the synthetic compounds has been carried out. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1687–1692, November, 2007.     

4-Hydroxy-2-quinolones. 168*. Synthesis,chemical and antitubercular properties of 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid pyrazin-2-ylamides

1-R-4-Hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid pyrazin-2-ylamides have been synthesized as potential antitubercular agents. In contrast to pyrimidin-2-ylamides the compounds prepared are brominated by molecular bromine in glacial acetic acid at position 6 of the quinolone ring rather than in the amide part of the molecule. The 1-N-allyl derivative behaves similarly but undergoes halocyclization to give 2-bromomethyl-5-oxo-1,2-dihydro-5H-oxazolo[3,2-a]quinoline-4-carboxylic acid pyrazin-2-ylamide. A comparative analysis of the antimycobacterial properties of the synthesized compounds and their isomeric pyrimidin-2-ylamides has been carried out.     

4-hydroxy-2-quinolones. 110. Bromination of 1-r-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid anilides

1-R-4-Hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid anilides have been prepared. It has been shown experimentally that these compounds are brominated by molecular bromine in glacial acetic acid at position 4 of the anilide fragment. The antitubercular properties of the compounds synthesized are discussed. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1508–1516, October, 2006.     

4-Hydroxy-2-quinolones. 154*. Pyrimidin- 2-ylamides of 1-r-4-hydroxy-2-oxo-1,2-dihydro- quinoline-3-carboxylic acids. synthesis,structure, and properties

The synthesis of a series of 1-R-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids pyrimidin-2-ylamides has been carried out with the aim of subsequent microbiological investigation. In acetic acid it was found that these compounds are brominated by 1 equivalent of bromine at position 5 of the pyrimidine ring. The only exception is the 1-allyl derivative which undergoes heterocyclization under these conditions to give 2-bromomethyl-5-oxo-1,2-dihydro-5H-oxazolo[3,2-a]quinoline-4-carboxylic acid pyrimidin-2-ylamide. The results of a study of the antitubercular activity of the synthesized compounds are presented.     

Chemistry of iminofurans: V. Synthesis,structure, and cyclization of 4-R-4-oxo-2-[2-(2-oxo-1,2-diphenylethylidene)hydrazino]but-2-enoic acids

Reactions of 1,2-diphenylethane-1,2-dione hydrazone with 4-aryl-2-hydroxy-4-oxobut-2-enoic and 2-hydroxy-5,5-dimethyl-4-oxohex-2-enoic acids provided 4-aryl-4-oxo-2-[2-(2-oxo-1,2-diphenylethylidene) hydrazino]but-2-enoic and 5,5-dimethyl-4-oxo-2-[2-(2-oxo-1,2-diphenylethylidene)hydrazino]hex-2-enoic acids. The acids derivatives can exist in solutions as Z- and β-enehydrazino-or β-ketohydrazone forms, and under the treatment with acetic anhydride they undergo cyclization into 5-aryl- and 5-tert-butyl-3-[2-(2-oxo-1,2-diphenylethylidene)hydrazono]-2,3-furandiones.     

4-hydroxy-2-quinolones. 202*. Synthesis, chemical and biological properties of 4-hydroxy-6,7-dimethoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid alkylamides

In continuation of the search for potential analgesics amongst 4-hydroxyquinol-2-one derivatives we have proposed and carried out a preparative method of synthesis of 4-hydroxy-6,7-dimethoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid alkylamides. It has been shown that bromination of 4-hydroxy-6,7-dimethoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid allylamide using an equivalent of molecular bromine occurs with a conventional addition of the halogen to the allyl double bond and not with halocyclization. The results of the study of the analgesic properties of the compounds prepared are presented.     

4-hydroxy-2-quinolones. 109. Alkylation of 4-substituted ethyl 2-oxo-1,2-dihydro-quinoline-3-carboxylates

The alkylation of the ethyl esters of 4-methyl, 4-chloro-, and 4-amino substituted 2-oxo-1,2-dihydroquinoline-3-carboxylic acid by ethyl iodide in the system DMF/K₂CO₃ has been studied. Features of the structure of the starting compounds and their effect on the ratio of the N-and O-alkyl products formed are discussed. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1502–1507, October, 2006.     

4-hydroxy-2-quinolones. 96. Synthesis and properties of 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid

Alkaline hydrolysis of the ethyl ester of 4-(cyanoethoxycarbonylmethyl)-2-oxo-1,2-dihydroquinoline-3-carboxylic acid is accompanied by decarboxylation with loss of two molecules of CO₂ and leads to 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 887–893, June, 2006.     

4-Hydroxy-2-quinolones 142. 4-Methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid anilides as potential diuretics

A large series of 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid anilides has been prepared as potential diuretic agents. The effect of all of the synthesized compounds on the urinary function of the kidney has been investigated. The appearance of a “structure — diuretic activity” relationship is discussed. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 239–245, February, 2008.     

4-hydroxy-2-quinolones. 178*. irreversible chemical modification of chinoxicaine at the position 4 of the quinolone ring

While continuing our investigation in improving the pharmaceutical activities of the local anesthetic Chinoxicaine we have studied the irreversible replacement of its 4-OH group for bioisosteric fragments. For this purpose the synthesis of a series of 4-R-2-oxo-1,2-dihydroquinoline-3-carboxylic acids 2-(diethylamino)ethylamide hydrochlorides has been carried out. The experimental data of the local anesthetic properties of the compounds obtained are given and discussed.     

4-Hydroxy-2-quinolones. 195*. Synthesis of novel,potential analgesics based on 4-(hetarylmethyl)amino-2-oxo-1,2-dihydro-quinoline-3-carboxylic acids

From the viewpoint of the method of bioisosteric replacement we have carried out the synthesis of a series of 4-(hetarylmethyl)amino-2-oxo-1,2-dihydroquinoline-3-carboxylic acids. For several examples it has been shown experimentally that the aromatic ring in the benzyl fragment of 4-benzylamino-2-oxo-1,2-dihydroquinoline-3-carboxylic acid can be replaced by an isosteric heterocycle without lowering the analgesic properties.     

Synthesis,nature of electronic transitions,and absorption spectra of the dye based on 4-(methyl-1-{2-[4-(1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)phenyl]-2-oxoethyl}pyridinium bromide

The reaction of 3-(4-bromoacetylphenyl)-1-methylquinolin-2(1Н)-one with pyridine and 4-methylpyridine has afforded the corresponding pyridinium salts. Condensation of 4-methyl-1-{2-[4-(1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)phenyl]-2-oxoethyl}pyridinium bromide with 4-dimethylaminobenzaldehyde has given a new biscyanine dye, 1-{1-[4-(1,2-dihydro-1-methyl-2-oxo-3-quinolinyl)benzoyl]-2-[4-(dimethylamino)-phenyl]ethynyl}-4-{2-[4-(dimethylamino)phenyl]ethynyl}pyridinium bromide. Its electronic spectrum has been analyzed, and quantum-chemical simulation of spatial and electronic structure of its possible isomers has been performed.     

Anomalous Beckmann Reaction in a Series of Oximes of 4-Aryl-2,7,7-trimethyl-5-oxo-5,6,7,8-tetrahydroquinolines in Polyphosphoric Acid. 2. Unexpected Synthesis of 3'-Ethoxycarbonyl-4',7',7'-trimethyl-4-oxo-2',6',7',8'-tetrahydrospiro(cyclohexa-2,5-diene-1,2'-pyrrolo[4,3,2-d,e]quinolines)

Oximes of 3-ethoxycarbonyl-4-halo(methoxy)phenyl-2,7,7-trimethyl-5-oxo-5,6,7,8-tetrahydroquinolines are converted in polyphosphoric acid (PPA) into 3'-ethoxycarbonyl-4',7',7'-trimethyl-4-oxo-2',6',7',8'-tetrahydrospiro(cyclohexa-2,5-diene-1,2'-pyrrolo[4,3,2-d,e]quinoline). An X-ray structural analysis has been carried out on one of the synthesized compounds.     

4-hydroxy-2-quinolones. 179*. Synthesis,structure, and anti-inflammatory activity of 4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinolin-3-ylacetic acid and its derivatives

The synthesis of 4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinolin-3-ylacetic acid has been carried out and the structure and acid properties studied. Preparative methods for its esterification and amidation are proposed. The anti-inflammatory properties of the synthesized compounds have been evaluated.     

4-Hydroxy-2-quinolones 148. Synthesis and antitubercular activity of 1-hydroxy-3-oxo-6,7-dihydro-3H,5H-pyrido[3,2,1-<Emphasis Type="Italic">ij</Emphasis>]quinoline-2-carboxylic acid N-R-amides

An improved method for the preparation of ethyl 1-hydroxy-3-oxo-6,7-dihydro-3H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylate has been proposed and a series of hetarylamides has been synthesized from it. A comparative analysis has been carried out of the antitubercular activities of the synthesized compounds with the active structural analogs 4-hydroxy-2-oxo-1,2-dihydroquinoline-3 and 1-hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo[3,2,1-ij]quinoline-2-carboxamides studied before. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1189–1202, August, 2008.     

Molecular Structure of 1-Ethyl-4-hydroxy-N-(6-hydroxybenzothiazolyl-2)-2-oxo-1,2-dyhydroquinoline-3-carboxamide

X-ray diffraction analysis of 1-ethyl-4-hydroxy-N-(6-hydroxybenzothiazolyl-2)-2-oxo-1,2-dihydroquinoline-3-carboxamide has been performed. In crystal, the compound exists as a 2-oxo-4-hydroxy tautomer.     

Substituted 3-and 5-formylpyridin-2-ones in the synthesis of 1-aryl-1, 6-naphthyridinone derivatives

New 1-aryl-6-[2-(dimethylamino)vinyl]4-oxo-1,4-dihydropyrimidine-5-carbonitriles and 4-arylamino-2-oxo-1,2-dihydropyridine-3-carbonitriles containing electron-withdrawing substituents in the benzene ring were synthesized from enamino amides and dimethylformamide dialkylacetals. The influence of various dimethylformamide acetals on the yield of 3-(4-chloro-anilino)-2-cyano-5-(dimethylamino)penta-2,4-dienoic acid N-(dimethylamino)methyl-ideneamide was investigated in the reaction of these acetals with 3-(4-chloroanilino)-2-cyanocrotonamide. New 4-arylamino-5-formyl-2-oxo-1,2-dihydropyridine-3-carbonitriles and 4-arylamino-2-oxo-1,2-dihydropyridine-3-carbaldehydes containing electron-withdrawing substituents in the benzene ring were synthesized. The latter compounds were converted into new substituted l,6-naphthyridinones by the action of various CH acids. A new approach to the synthesis of 4-(4-fluoroanilino)-5-formyl-2-oxo-1,2-dihydropyridine-3-carbonitrile using dimethylformamide diisopropylacetal under mild conditions was developed. The comparative reactivity of the formyl group in the reactions of 4-arylamino-5-formyl-2-oxo-1,2-dihydropyridine-3-carbonitriles and in 4-arylamino-2-oxo-1,2-dihydropyridine-3-carb-aldehydes with malononitrile was determined using HPLC.     

4-Hydroxy-2-quinolones 144. Alkyl-, arylalkyl-, and arylamides of 2-hydroxy-4-oxo-4H-pyrido[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidine-3-carboxylic acid and their diuretic properties

Alkyl-, arylalkyl-, and arylamides of 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid were prepared with a view to establishing a structure-biological activity relationship. A comparative analysis has been made of their diuretic properties and those of the structurally similar 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 718–729, May, 2008.     

4-hydroxy-2-quinolones. 191.* synthesis,tautomerism and biological activity of benzimidazol-2-ylamides of 1-r-4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids

A series of benzimidazol-2-ylamides of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acids was prepared in a search for biologically active compounds. These compounds exist in the crystal exclusively in the amide form, while in solution amide↔imide tautomerism is observed. The results of a study of the antithyroid and antituberculosis activities of these compounds are given.