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. 180*. Synthesis,chemical reactions,and analgesic activity of 1-allyl-4-hydroxy-6,7-dimethoxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid alkylamides

A targeted synthesis was carried out of a series of 1-allyl-4-hydroxy-6,7-dimethoxy-2-oxo-1,2-di-hydroquinoline-3-carboxylic acid alkylamides which show interest for biological study as potential analgesics. It was found that, in the presence of one equivalent of bromine, the compounds indicated undergo halocyclization to the corresponding 2-bromomethyl-7,8-dimethoxy-5-oxo-1,2-dihydro-5H-oxa-zolo[3,2-a]quinoline-4-carboxylic acid alkylamides. However, with an excess of bromine the reaction occurs somewhat differently and concludes with the formation of complexes of bromine with 4-alkyl-carbamoyl-2-bromomethyl-5-hydroxy-7,8-dimethoxy-1,2-dihydrooxazolo[3,2-a]quinolinium ditri- bromides. According to the results of pharmacological screening there are found compounds within the substances discovered with high analgesic activity.     

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. 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. 92. Reaction of 1-R-4-chloro-3-ethoxycarbonyl-2-oxo-1,2-dihydroquinolines with anilines

A preparative method is proposed and the synthesis of 4-arylamino-2-oxo-1,2-dihydroquinolines has been effected. An X-ray structural investigation of 4-(4-chlorophenylamino)-2-oxo-1-propyl-1,2-dihydroquinoline-3-carboxylic acid has been carried out enabling the ease of decarboxylating such compounds to be substantiated. Results are given of a study of the anti-inflammatory activity of the synthesized compounds. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 386–395, March, 2006.     

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 123. Amidation of 2-bromomethyl-5-oxo-1,2-dihydro-5H-oxazolo[3,2-<Emphasis Type="Italic">a</Emphasis>]-quinoline-4-carboxylic acid

The reaction of 2-bromomethyl-5-oxo-1,2-dihydro-5H-oxazolo[3,2-a]quinoline-4-carboxylic acid with thionyl chloride is accompanied by a transformation of the oxazoloquinolone ring to give 4-chloro-1-(2,3-dichloropropyl)-2-oxo-1,2-dihydroquinoline-3-carboxylic acid chloride. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1034–1042, July, 2007.     

4-Hydroxy-2-quinolones. 174.* Hydrochlorides of [(alkylamino)alkyl]amides of 1-allyl- 4-hydroxy-6,7-dimethoxy-2-oxo-1,2-dihydro- quinoline-3-carboxylic acid – a new class of opioid receptor antagonists

Hydrochlorides salts of [(alkylamino)alkyl]amides of 1-allyl-4-hydroxy-6,7-dimethoxy-2-oxo-1,2-di-hydroquinoline-3-carboxylic acid were synthesized as potential biologically active compounds. Pharmacological testing showed promise for using these compounds to develop new highly efficient opioid receptor antagonists.     

4-hydroxy-2-quinolones. 176*. 4-R-2-oxo-1,2-dihydroquinoline-3-carboxylic acids. synthesis,physicochemical and biological properties

We have carried out the synthesis and a comparative analysis of the acidic properties of a large group of 4-R-2-oxo-1,2-dihydroquinoline-3-carboxylic acids. Features of the recorded NMR spectra of these compounds are discussed together with their analgesic properties.     

Synthesis of 6-amino-2-aryl-1,2-dihydro-3H-pyrido[2,3-d]pyrimidin-4-one derivatives

This paper reports the synthesis of new pyrido[2,3-d]pyrimidin-4-one derivatives as diuretic agents. Starting with 1,2-dihydro-5-nitro-2-oxo-3-pyridinecarboxylic acid 1 , ethyl 2-ethoxy-5-nitro-3-pyridincarboxylate 4 was obtained. Compound 4 reacts with ammonia, methylamine or S-methylpseudothiourea to give the respective 2-amino-5-nitro-3-pyridinecarboxamide derivatives 5 and 6 or 2-methylthio-6-nitro-3H-pyrido[2,3-d]pyrimidin-4-one 8. Treating carboxamide 5 with arylaldehydes and zinc dichloride, new 2-aryl-1,2-dihydro-6-nitro-3H-pyrido[2,3-d]pyrimidin-4-ones 9 were synthetised. These compounds reduced with iron(II) hydroxide gave 6-amino-2-aryl-1,2-dihydro-3H-pyrido[2,3-d]pyrimidin-4-ones 10 as expected.     

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. 112. Reaction of 2-ethoxycarbonylmethyl-4H-3,1-benzoxazin-4-one with active methylene compounds

The reaction of 2-ethoxycarbonylmethyl-4H-3,1-benzoxazin-4-one with malononitrile in dry pyridine leads to 1-hydroxy-3,6-dioxo-4,6-dihydro-3H-pyrimido[1,2-a]quinoline-5-carbonitrile. Acetoacetic and cyanoacetic esters under analogous conditions form anilides of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid while diethyl malonate gives N,N′-di-2-carboxyanilides of malonic acid. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 75–79, January, 2007.     

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.     

4-Hydroxy-2-quinolones 150*. Efficient synthesis,structure, and biological activities of 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid alkyl amides

A simple and efficient method for preparing 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid alkyl amides is proposed. The results of a study of the diuretic activity of the compounds synthesized are reported. *For communication 149 see [1]. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1841-1848, December, 2008.     

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. 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.     

4-Hydroxyquinol-2-ones. 87. Unusual Synthesis of 1-R-4-Hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic Acid Pyridylamides

4-Chloro-2-oxo-1,2-dihydroquinoline-3-carboxylic acids and their esters react with aminopyridines in refluxing DMF to give the corresponding 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylic acid pyridylamides. Their structures were proved by ¹H NMR and mass spectroscopy, counter synthesis, and by X-ray analysis. A possible mechanism is proposed for the indicated chemical reaction. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1362–1371, September, 2005.     

A novel synthetic route to 1,2-dimethyl-5-phenyl-1H-imidazo[4,5-b]pyridin-7-ol

Heating a mixture of 4-amino-1,2-dimethyl-1H-imidazole-5-carboxylic acid ethyl ester with ethyl benzoyl acetate resulted in the formation of 8-ethoxycarbonyl-6,7-dimethyl-4-oxo-2-phenylimidazo[1,5-a]pyrimidin-5-ium, hydroxide, inner salt. This compound was then transformed into 1,2-dimethyl-5-phenyl-1H-imidazo-[4,5-b]pyridin-7-ol via several intermediates. A number of structurally interesting compounds were also isolated during the course of this work. Thus, the target ring system was formed by a circuitous series of ring-chain tautomerizations/rearrangements.     

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. 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.