- [Show abstract] [Hide abstract] ABSTRACT: Reactions of 5-carboxy and 4-methylphenylene-1,3-bisdiazonium tetrafluoroborates with amides and nitriles of acrylic and methacrylic acids in the presence of chloride, bromide, and thiocyanate anions proceed as anionarylation at one of the diazo groups and nucleophilic substitution at another one. With 4-methylphenylene- 1,3-bisdiazonium tetrafluoroborate as the arylating agent, the anionarylation and the Sandmeyer reaction occur involving para- and ortho-positioned diazo groups, respectively.
- [Show abstract] [Hide abstract] ABSTRACT: Studies have been conducted of the reactions of 7-phenyl-3,7-dihydro-4H-pyrazolo[3,4-d][1,2,3]triazin-4-one with alkyl halides and formaldehyde, that occurred with retention of the pyrazolotriazine structure. Ethyl 2-(4-oxo-7-phenyl-4,7-dihydro-3H-pyrazolo[3,4-d][1,2,3]triazin-3-yl)- acetate was prepared by the reaction of 7-phenyl-3,7-dihydro-4H-pyrazolo[3,4-d][1,2,3]triazin-4-one with ethyl chloroacetate. It was used to synthesize the corresponding hydrazide with the aim of introducing the pyrazole or 1,3,4-oxadiazole fragments in the side chain of a bicyclic system.
- [Show abstract] [Hide abstract] ABSTRACT: This article represents the research of the interaction of 1-phenyl-5-chloro-1H-pyrazole-4-carboxamide and 1-phenyl-N-formyl-5-chloro-1H-pyrazole-4-carboxamide with hydrazine hydrate in order to get pyrazole derivatives as potential bioactive substances. It has been found that during the short (~40 min) boiling of 1-phenyl-5-chloro-1H-pyrazole-4-carboxamide with hydrazine hydrate a previously unknown 5-hydrazino-1-phenyl-1Hpyrazole-4-carbohydrazide with the yield of 50% is formed. The further boiling (~15 h) of the product obtained with hydrazine hydrate leads unexpectedly to 1-phenyl-1H-pyrazole-4-carbohydrazide. The probable mechanism of its obtaining, which includes dimerization of the prototropic isomer formed while cleaving the hydrazine molecule and the further elimination of the nitrogen molecule, has been considered. When boiling with hydrazine hydrate for 3 hours 1-Phenyl-N-formyl-5-chloro-1H-pyrazole-4-carboxamide gives 5-amino-1-phenyl-1H-pyrazole-4-carbohydrazide. At fist, obviously, N-[(5-hydrazino-1-phenyl-1H-pyrazol-4-yl) carbonyl]formamide is formed with further cyclization into pyrazole[3,4-d][1,2,3]triazin-4-one. The latter eliminates the nitrogen molecule when heating with the formation of the reactive 4-carbonyl-1-phenyl-4,5-dihydro-1H-pyrazole-5-imine. Addition of hydrazine to it leads to 5-amino-1-phenyl-1H-pyrazole-4-carbohydrazide. The composition of all compounds synthesized has been proven by elemental analysis and the structure has been confimed by spectroscopic methods.
- [Show abstract] [Hide abstract] ABSTRACT: Reaction of 2-methoxy-5-morpholino-1,3-oxazole-4-carbonitrile with benzylamine, phenethylamine and phenylhydrazine results in the new substituted 5-amino-2,3-dihydro-1H-imidazol-2-ones.
- [Show abstract] [Hide abstract] ABSTRACT: The reaction of 7-phenyl-7H-pyrazolo[3,4-d][1,2,3]triazin-4-ol with thionyl chloride has been studied in the presence and absence of dimethyl formamide. It was found that heating the compound with thionyl chloride in the absence of dimethyl formamide gave 5-amino-1-phenyl-1H-pyrazole-4-carboxylic acid chloride and in its presence a mixture of 5-chloro-N-formyl-1-phenyl-1H-pyrazole-4-carboxamide, 5-chloro-1-phenyl-1H-pyrazole-4-carboxamide, and 4-chloro-6-(5-chloro-1-phenyl-1H-pyrazol-4-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine.
- [Show abstract] [Hide abstract] ABSTRACT: Anticancer activity of 1,3-thiazole (I - III) and 1,3-oxazole (IV - VI) derivatives have been studied which contain a sulfonyl group in position 4 (I, IV), a sulfonyl group in position 5 (V), a sulfonamide group in position 5 (VI), 2,4-disulfonyl derivatives (II) and 4,5-disulfonyl derivatives (III). The highest level of anticancer activity was detected for a many 4-arylsulfonyl-5-piperazin-1,3-thiazoles. Using multidimensional scaling of the correlation matrix of distances in visualizing patterns of activity allows to divide analyzed compounds into three patterns. The first pattern includes thiazoles type (I, II), the second – a 5-arylsulfonyl-4-cyano-1,3-oxazoles of type (V, VI), the third – thiazoles and oxazoles with piperazine moiety in position 5 (I, IV). This indicate three different mechanisms of action. A data set of 3240 unique compounds were collected from different published papers and PubChem. In the pre-processing stage all molecules were processed by the Chemaxon standardizer. 2D coordinates of atoms were recalculated, counter ions and salts were removed from molecular structures, molecules were neutralized. Data sets were then filtered from duplicates. 3D structures were generated using Chemaxon software and stored in SDF format. The molecular descriptors were calculated by Dragon program. QSAR methodologies used Associative Neural Networks (ASNN). The accuracy of all individual models was estimated using 5-fold cross-validation procedures. The influence of the descriptor set on the model accuracy was evaluated. Descriptors were selected by “pruning methods” implemented in ASNN software. Obtained model accuracy Ac were in the range 0.96-0.97. The activity of newly synthesized 1,3 – thiazole and 1,3 – oxazole derivates were predicted by created QSAR models. The anticancer activity of these compounds was also studied in the framework of the international program of the National Institute of Health, USA - DTP (Developmental Therapeutic Programm) of the National Cancer Institute (NCI). The results of prediction are shown in Fig. 1. The compounds were predicted with total good accuracy, Ac=0.694 (for active compounds - Ac=0.667). However, the anticancer activity of 1,3–oxazole derivatives was predicted by QSAR models more better than that for 1,3 – thiazole derivatives. Therefore, the created QSAR models can be used for prediction of anticancer activity of 1,3 – oxazole derivates.
- [Show abstract] [Hide abstract] ABSTRACT: The reaction of 2-acylamino-3,3-dichloroacrylonitriles with arylhydrazines in tetrahydrofuran upon heating was investigated. It led to previously unknown 3-acylamino-2-arylhydrazono-3-cyano-2,3-di-hydro-1H-indoles.
- [Show abstract] [Hide abstract] ABSTRACT: Various approaches to the synthesis of new derivatives of diethyl 5-mercapto-2-R-1,3-oxazole-4-ylphosphonates were considered. The behavior of these compounds in the presence of mineral acids and alkalis resulting in the synthesis of previously unknown 5-mercapto-2-R-1,3-oxazole-4-ylphosphonic acids was studied.
- [Show abstract] [Hide abstract] ABSTRACT: The interaction of 7-aryl-7H-pyrazolo[3,4-d][1,2,3]triazin-4-ols with phosphorus pentoxide or pentasulfide leads to the formation of 6-(5-amino-1-aryl-1H-pyrazol-4-yl)-1-aryl-1H,4H-pyrazolo[3,4-d][1,3]oxazin-4-ones and 6-(5-amino-1-aryl-1H-pyrazol-4-yl)-1-aryl-1H,4H-pyrazolo[3,4-d][1,3]thiazine-4-thiones, respectively. Reaction with phosphorus oxychloride leads to 1-aryl-5-chloro-1H-pyrazole-4-carbonyl chlorides, from which the corresponding amides, hydrazides, and substituted 1,3,4-oxadiazoles were synthesized.
- [Show abstract] [Hide abstract] ABSTRACT: The reaction of substituted 2-oxo-2,3-dihydro-1H-imidazole-4-carbonitriles with Lawesson’s reagent gave new compounds of the fused imidazo[4,5-d][1,3,2]diazaphosphinine system.
- [Show abstract] [Hide abstract] ABSTRACT: 5-Alkylamino-1,3-oxazole-4-carbonitriles containing a 2-phthalimidoethyl or 3-phthalimidopropyl substituent at position 2 of the oxazole ring were synthesized. In the reaction of 5-(morpholin-4-yl)-2-(2-phthalimidoethy)l-1,3-oxazole-4-carbonitrile with hydrazine hydrate, 2-(2-aminoethyl)-5-(morpholin-4-yl)-1,3-oxazole-4-carbonitrile is formed. In the case of the 3-phthalimidopropyl analog, the recyclization product 3-amino-2-(morpholin-4-ylcarbonyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole is formed.
- [Show abstract] [Hide abstract] ABSTRACT: Hydrazinolysis of phthalimidoethyloxazole (VIIIc) affords the expected free amine (IX), whilst a recyclization product (X) is formed in the hydrazinolysis of phthalimidopropyl analogue (VIIIg).
- [Show abstract] [Hide abstract] ABSTRACT: The preparation of 7-thioxoimidazo[1,2-c]pyrimidines (III) and their regioselective intramolecular condensation furnishing products (IV) are described for the first time.
- [Show abstract] [Hide abstract] ABSTRACT: A method for the synthesis of a new 4-phenylsulfonyl-substituted 3-aminopyrrole was developed and related pyrrolo[3,2-d]pyrimidine derivatives were synthesized.
- [Show abstract] [Hide abstract] ABSTRACT: The purpose-directed synthesis of a new heterocyclic system, 7,8-dihydroimidazo[1,2-c][1,3]thia- zolo[4,5-e]pyrimidine has been carried out based on the successive interaction of available 2-(aroyl- aminocyanomethylene)imidazolidines with hydrogen sulfide and triethyl orthoformate with subsequent intramolecular cyclocondensation of the obtained 8-aroylamino-7-thioxo-1,2,3,7-tetrahydroimidazo- [1,2-c]pyrimidines under the action of phosphorus pentasulfide or polyphosphoric acid.
- [Show abstract] [Hide abstract] ABSTRACT: On the basis of methyl esters of 2-aryl-5-hydrazino-1,3-oxazole-4-carboxylic acids the earlier unknown methyl esters of 2-aryl-5-(3,5-dimethyl-1H-pyrazol-1-yl)-1,3-oxazole-4-carboxylic acids as well as their functional derivatives were synthesized. The latter were used for further transformations, in particular, for introducing the residues of highly basic aliphatic amines into the 5 position of oxazole, and the oxazol-2-yl moiety into the 4 position of the oxazole ring.
- [Show abstract] [Hide abstract] ABSTRACT: The products of addition of amidines to accessible 5-arylamino-4-cyano-1,3-oxazoles at heating in acetic acid undergo recyclization and afford new derivatives of 6-amino-5-acylaminopyrimidin-4-one, whose structure was reliably established using X-ray diffraction studies.
- [Show abstract] [Hide abstract] ABSTRACT: Reactions of accessible 5-alkylamino- and 5-arylamino-1,3-oxazole-4-carbonitriles with hydrazine hydrate on heating involved a complex transformation sequence resulting in the formation of 3,4,5-triaminopyrazole derivatives. The structure of the products was confirmed by their cyclocondensation with acetylacetone, leading to 2-alkyl(aryl)amino-3-acylamino-5,7-dimethylpyrazolo[1,5-a]pyrimidines which were identified by NMR spectroscopy using COSY, NOESY, HMQC, and HMBC techniques.
National Academy of Sciences of Ukraine
Kievo, Kyiv City, Ukraine
- Institute of Bioorganic Chemistry and Petrochemistry