973 research outputs found

    Structure of 2-Methyl-5,6,7-triphenyl-6,7-dihydropyrazolo[2,3-\u3cem\u3ea\u3c/em\u3e]pyrimidine

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    C25H21N3, Mr = 363.46, monoclinic, P21/n, a = 9.245 (2), b = 23.502 (5), c = 9.340 (2) Γ…, Ξ²= 103.50(3)Β°, V=1973.3(2) Γ…3, Z=4, Dx= 1.220 (2) g cm-3, Ξ» (Mo KΞ± )= 0.71069 Γ…, ΞΌ = 0.068 cm-1, F(000) = 768, T= 292 K, R = 0.091 for 1442 unique observed reflections. The dihydropyrimidine ring adopts a distorted sofa conformation. The aryl substituents on the saturated C atoms have an axial orientation

    Π‘ΠΈΠ½Ρ‚Π΅Π· 7-Π°Ρ€ΠΈΠ»-6,7-Π΄ΠΈΠ³Ρ–Π΄Ρ€ΠΎΡ‚Π΅Ρ‚Ρ€Π°Π·ΠΎΠ»ΠΎ[1,5-a]ΠΏΡ–Ρ€ΠΈΠΌΡ–Π΄ΠΈΠ½-5(4H)-ΠΎΠ½Ρ–Π²

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    Arylmethyliden derivatives of 2,2-dimethyl-1,3-dioxane-4,6-dione; Meldrum`s acid; 6,7-dihydro-7-aryltetrazolo [1,5-a]pyrimidin-5(4H)-ones; synthesis; pharmacological activityCyclocondensations of 1H-tetrazol-5-amine with methylcinnamates, arylmethyliden malonic acids and arylmethyliden derivatives of 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum`s acid) proceed regioselectively and lead to formation of 7-aryl-6,7-dyhidrotetrazolo[1,5-a]pyrimidin-5(4H)-ones. The direction of cyclization corresponds to the interaction of the carbon atom in Ξ²-position of the unsaturated carbonyl compounds with the endocyclic nitrogen atom and the carbonyl group with amino group in the aminoazole molecule. Compounds of the isomeric structure in any of the experiments have been not identified. The structures and composition of the newly synthesized tetrazolo[1,5-a]pyrimidin-5(4H)-ones have been confirmed by elemental analysis, infrared spectroscopy (IR), nuclear magnetic resonance on protones (1H NMR) and mass spectra data. Virtual screening of 7-aryl-6,7-dihydrotetrazolo[1,5-a]pyrimidin-5(4H)-ones carried out using the PASS programme for 780 types of the pharmacological action has demonstrated that it is expedient to test these compounds by their analgesic and anti-inflammatory activity, as well as as potential agents for the treatment of heart failure.ЦиклокондСнсации 1Н-Ρ‚Π΅Ρ‚Ρ€Π°Π·ΠΎΠ»-5-Π°ΠΌΠΈΠ½Π° с ΠΌΠ΅Ρ‚ΠΈΠ»Ρ†ΠΈΠ½Π½Π°ΠΌΠ°Ρ‚Π°ΠΌΠΈ, Π°Ρ€ΠΈΠ»ΠΌΠ΅Ρ‚ΠΈΠ»ΠΈΠ΄Π΅Π½ΠΌΠ°Π»ΠΎΠ½ΠΎΠ²Ρ‹ΠΌΠΈ кислотами ΠΈ Π°Ρ€ΠΈΠ»ΠΌΠ΅Ρ‚ΠΈΠ»ΠΈΠ΄Π΅Π½ΠΏΡ€ΠΎΠΈΠ·Π²ΠΎΠ΄Π½Ρ‹ΠΌΠΈ 2,2-Π΄ΠΈΠΌΠ΅Ρ‚ΠΈΠ»-1,3-диоксан-4,6-Π΄ΠΈΠΎΠ½Π° (кислоты ΠœΠ΅Π»ΡŒΠ΄Ρ€ΡƒΠΌΠ°) происходят рСгиосСлСктивно ΠΈ приводят ΠΊ ΠΎΠ±Ρ€Π°Π·ΠΎΠ²Π°Π½ΠΈΡŽ 7-Π°Ρ€ΠΈΠ»-6,7-Π΄ΠΈΠ³ΠΈΠ΄Ρ€ΠΎΡ‚Π΅Ρ‚Ρ€Π°Π·ΠΎΠ»ΠΎ[1,5-a]ΠΏΠΈΡ€ΠΈΠΌΠΈΠ΄ΠΈΠ½- 5(4Н)-ΠΎΠ½ΠΎΠ². ΠΠ°ΠΏΡ€Π°Π²Π»Π΅Π½Π½ΠΎΡΡ‚ΡŒ формирования ΠΏΠΈΡ€ΠΈΠΌΠΈΠ΄ΠΈΠ½ΠΎΠ²ΠΎΠ³ΠΎ ΠΊΠΎΠ»ΡŒΡ†Π° соотвСтствуСт Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡ‚Π²ΠΈΡŽ Π°Ρ‚ΠΎΠΌΠ° ΡƒΠ³Π»Π΅Ρ€ΠΎΠ΄Π°, находящСгося Π² Ξ²-ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΠΈ нСнасыщСнного ΠΊΠ°Ρ€Π±ΠΎΠ½ΠΈΠ»ΡŒΠ½ΠΎΠ³ΠΎ соСдинСния, с эндоцикличСским Π°Ρ‚ΠΎΠΌΠΎΠΌ Π°Π·ΠΎΡ‚Π°, Π° ΠΊΠ°Ρ€Π±ΠΎΠ½ΠΈΠ»ΡŒΠ½ΠΎΠΉ Π³Ρ€ΡƒΠΏΠΏΡ‹ – с Π°ΠΌΠΈΠ½ΠΎΠ³Ρ€ΡƒΠΏΠΏΠΎΠΉ Π² ΠΌΠΎΠ»Π΅ΠΊΡƒΠ»Π΅ Π°ΠΌΠΈΠ½ΠΎΠ°Π·ΠΎΠ»Π°. БоСдинСния ΠΈΠ·ΠΎΠΌΠ΅Ρ€Π½ΠΎΠ³ΠΎ строСния Π½ΠΈ Π² ΠΎΠ΄Π½ΠΎΠΌ ΠΈΠ· экспСримСнтов Π½Π΅ выявлСны. Бостав ΠΈ строСниС Π²ΠΏΠ΅Ρ€Π²Ρ‹Π΅ синтСзированных Ρ‚Π΅Ρ‚Ρ€Π°Π·ΠΎΠ»ΠΎ[1,5-a]ΠΏΠΈΡ€ΠΈΠΌΠΈΠ΄ΠΈΠ½-5(4Н)-ΠΎΠ½ΠΎΠ² Π΄ΠΎΠΊΠ°Π·Π°Π½Ρ‹ ΠΏΡ€ΠΈ ΠΏΠΎΠΌΠΎΡ‰ΠΈ элСмСнтного Π°Π½Π°Π»ΠΈΠ·Π°, инфракрасной спСктроскопии (ИК), ядСрного ΠΌΠ°Π³Π½ΠΈΡ‚Π½ΠΎΠ³ΠΎ рСзонанса Π½Π° ΠΏΡ€ΠΎΡ‚ΠΎΠ½Π°Ρ… (ЯМР 1Н) ΠΈ массспСктромСтрии. Π’ΠΈΡ€Ρ‚ΡƒΠ°Π»ΡŒΠ½Ρ‹ΠΉ скрининг ΠΏΠΎΠ»ΡƒΡ‡Π΅Π½Π½Ρ‹Ρ… 7-Π°Ρ€ΠΈΠ»-6,7-Π΄ΠΈΠ³ΠΈΠ΄Ρ€ΠΎΡ‚Π΅Ρ‚Ρ€Π°Π·ΠΎΠ»ΠΎ[1,5-a]ΠΏΠΈΡ€ΠΈΠΌΠΈΠ΄ΠΈΠ½-5(4Н)-ΠΎΠ½ΠΎΠ², ΠΏΡ€ΠΎΠ²Π΅Π΄Π΅Π½Π½Ρ‹ΠΉ с использованиСм ΠΏΡ€ΠΎΠ³Ρ€Π°ΠΌΠΌΡ‹ PASS ΠΏΠΎ 780 Π²ΠΈΠ΄Π°ΠΌ фармакологичСского дСйствия, ΠΏΠΎΠΊΠ°Π·Π°Π», Ρ‡Ρ‚ΠΎ эти соСдинСния цСлСсообразно Ρ‚Π΅ΡΡ‚ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ ΠΏΠΎ показатСлям Π°Π½Π°Π»ΡŒΠ³Π΅Ρ‚ΠΈΡ‡Π΅ΡΠΊΠΎΠΉ ΠΈ ΠΏΡ€ΠΎΡ‚ΠΈΠ²ΠΎΠ²ΠΎΡΠΏΠ°Π»ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΠΉ активности, Π° Ρ‚Π°ΠΊΠΆΠ΅ ΠΊΠ°ΠΊ ΠΏΠΎΡ‚Π΅Π½Ρ†ΠΈΠ°Π»ΡŒΠ½Ρ‹Π΅ срСдства для лСчСния сСрдСчной нСдостаточности.ЦиклокондСнсації 1Н-Ρ‚Π΅Ρ‚Ρ€Π°Π·ΠΎΠ»-5-Π°ΠΌΡ–Π½Ρƒ Π· ΠΌΠ΅Ρ‚ΠΈΠ»Ρ†ΠΈΠ½Π°ΠΌΠ°Ρ‚Π°ΠΌΠΈ, Π°Ρ€ΠΈΠ»ΠΌΠ΅Ρ‚ΠΈΠ»Ρ–Π΄Π΅Π½ΠΌΠ°Π»ΠΎΠ½ΠΎΠ²ΠΈΠΌΠΈ кислотами Ρ‚Π° Π°Ρ€ΠΈΠ»ΠΌΠ΅Ρ‚ΠΈΠ»Ρ–Π΄Π΅Π½ΠΏΠΎΡ…Ρ–Π΄Π½ΠΈΠΌΠΈ 2,2-Π΄ΠΈΠΌΠ΅Ρ‚ΠΈΠ»-1,3-діоксан-4,6-Π΄Ρ–ΠΎΠ½Ρƒ (кислоти ΠœΠ΅Π»ΡŒΠ΄Ρ€ΡƒΠΌΠ°) Π²Ρ–Π΄Π±ΡƒΠ²Π°ΡŽΡ‚ΡŒΡΡ рСгіосСлСктивно Ρ‚Π° ΠΏΡ€ΠΈΠ²ΠΎΠ΄ΡΡ‚ΡŒ Π΄ΠΎ утворСння 7-Π°Ρ€ΠΈΠ»-6,7-Π΄ΠΈΠ³Ρ–Π΄Ρ€ΠΎΡ‚Π΅Ρ‚Ρ€Π°Π·ΠΎΠ»ΠΎ[1,5-a]ΠΏΡ–Ρ€ΠΈΠΌΡ–Π΄ΠΈΠ½-5(4Н)-ΠΎΠ½Ρ–Π².ΠΠ°ΠΏΡ€Π°Π²Π»Π΅Π½Ρ–ΡΡ‚ΡŒ формування ΠΏΡ–Ρ€ΠΈΠΌΡ–Π΄ΠΈΠ½ΠΎΠ²ΠΎΠ³ΠΎ ΠΊΡ–Π»ΡŒΡ†Ρ Π²Ρ–Π΄ΠΏΠΎΠ²Ρ–Π΄Π°Ρ” Π²Π·Π°Ρ”ΠΌΠΎΠ΄Ρ–Ρ— Π°Ρ‚ΠΎΠΌΠ° ΠΊΠ°Ρ€Π±ΠΎΠ½Ρƒ Ρƒ Ξ²-ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½Π½Ρ– нСнасичСної ΠΊΠ°Ρ€Π±ΠΎΠ½Ρ–Π»ΡŒΠ½ΠΎΡ— сполуки Π· Π΅Π½Π΄ΠΎΡ†ΠΈΠΊΠ»Ρ–Ρ‡Π½ΠΈΠΌ Π°Ρ‚ΠΎΠΌΠΎΠΌ Π½Ρ–Ρ‚Ρ€ΠΎΠ³Π΅Π½Ρƒ, Π° ΠΊΠ°Ρ€Π±ΠΎΠ½Ρ–Π»ΡŒΠ½ΠΎΡ— Π³Ρ€ΡƒΠΏΠΈ – Π· Π°ΠΌΡ–Π½ΠΎΠ³Ρ€ΡƒΠΏΠΎΡŽ Π² ΠΌΠΎΠ»Π΅ΠΊΡƒΠ»Ρ– Π°ΠΌΡ–Π½ΠΎΠ°Π·ΠΎΠ»Ρƒ. Π‘ΠΏΠΎΠ»ΡƒΠΊ Ρ–Π·ΠΎΠΌΠ΅Ρ€Π½ΠΎΡ— Π±ΡƒΠ΄ΠΎΠ²ΠΈ Π² ΠΆΠΎΠ΄Π½ΠΎΠΌΡƒ Π· СкспСримСнтів Π½Π΅ виявлСно. Π‘ΠΊΠ»Π°Π΄ Ρ‚Π° Π±ΡƒΠ΄ΠΎΠ²Ρƒ Π²ΠΏΠ΅Ρ€ΡˆΠ΅ синтСзованих Ρ‚Π΅Ρ‚Ρ€Π°Π·ΠΎΠ»ΠΎ[1,5-a]ΠΏΡ–Ρ€ΠΈΠΌΡ–Π΄ΠΈΠ½-5(4Н)-ΠΎΠ½Ρ–Π² Π΄ΠΎΠ²Π΅Π΄Π΅Π½ΠΎ Π·Π° допомогою Π΅Π»Π΅ΠΌΠ΅Π½Ρ‚Π½ΠΎΠ³ΠΎ Π°Π½Π°Π»Ρ–Π·Ρƒ, Ρ–Π½Ρ„Ρ€Π°Ρ‡Π΅Ρ€Π²ΠΎΠ½ΠΎΡ— спСктроскопії (Π†Π§), ядСрного ΠΌΠ°Π³Π½Ρ–Ρ‚Π½ΠΎΠ³ΠΎ рСзонансу Π½Π° ΠΏΡ€ΠΎΡ‚ΠΎΠ½Π°Ρ… (ЯМР 1Н) Ρ‚Π° мас-спСктромСтрії. Π’Ρ–Ρ€Ρ‚ΡƒΠ°Π»ΡŒΠ½ΠΈΠΉ скринінг 7-Π°Ρ€ΠΈΠ»-6,7-Π΄ΠΈΠ³Ρ–Π΄Ρ€ΠΎΡ‚Π΅Ρ‚Ρ€Π°Π·ΠΎΠ»ΠΎ[1,5-a]ΠΏΡ–Ρ€ΠΈΠΌΡ–Π΄ΠΈΠ½-5(4Н)-ΠΎΠ½Ρ–Π², ΠΏΡ€ΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠΉ Ρ–Π· використанням ΠΏΡ€ΠΎΠ³Ρ€Π°ΠΌΠΈ PASS Π·Π° 780 Π²ΠΈΠ΄Π°ΠΌΠΈ Ρ„Π°Ρ€ΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³Ρ–Ρ‡Π½ΠΎΡ— Π΄Ρ–Ρ—, засвідчив, Ρ‰ΠΎ Ρ†Ρ– сполуки Π΄ΠΎΡ†Ρ–Π»ΡŒΠ½ΠΎ тСстувати Π·Π° ΠΏΠΎΠΊΠ°Π·Π½ΠΈΠΊΠ°ΠΌΠΈ Π°Π½Π°Π»Π³Π΅Ρ‚ΠΈΡ‡Π½ΠΎΡ— активності, Π° Ρ‚Π°ΠΊΠΎΠΆ як ΠΏΠΎΡ‚Π΅Π½Ρ†Ρ–ΠΉΠ½Ρ– засоби для лікування сСрцСвої нСдостатності

    Observation of Macroscopic Structural Fluctuations in bcc Solid 4He

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    We report neutron diffraction studies of low density bcc and hcp solid 4He. In the bcc phase, we observed a continuous dynamical behaviour involving macroscopic structural changes of the solid. The dynamical behaviour takes place in a cell full of solid, and therefore represents a solidsolid transformation. The structural changes are consistent with a gradual rotation of macroscopic grains separated by low angle grain boundaries. We suggest that these changes are triggered by random momentary vibrations of the experimental system. An analysis of Laue diffraction patterns indicates that in some cases these structural changes, once initiated by a momentary impulse, seem to proceed at a constant rate over times approaching an hour. The energy associated with these macroscopic changes appears to be on the order of kT. Under similar conditions (temperature and pressure), these effects were absent in the hcp phase.Comment: 14 pages, 6 figure, accepted for PR

    Π₯Ρ–ΠΌΡ–Ρ‡Π½Ρ– властивості 3-(5-Π°ΠΌΡ–Π½ΠΎ-1Н-1,2,4-Ρ‚Ρ€ΠΈΠ°Π·ΠΎΠ»-1-Ρ–Π»)- Ρ‚Π° 3-(2-Π°ΠΌΡ–Π½ΠΎ-1Н-Π±Π΅Π½Π·ΠΎ[d]Ρ–ΠΌΡ–Π΄Π°Π·ΠΎΠ»-1-Ρ–Π»)-3-Ρ„Π΅Π½Ρ–Π»ΠΏΡ€ΠΎΠΏΠ°Π½Π³Ρ–Π΄Ρ€Π°Π·ΠΈΠ΄Ρ–Π²

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    Reactions of 3-(5-amino-1H-1,2,4-triazol-1-yl)- and 3-(2-amΡ–no-1H-benzo[d]Ρ–mΡ–dazol-1-yl)-3-phenylpropanehydrazides with carbonyl electrophiles such as acetylacetone, aromatic and heterocyclic aldehydes in the alcoholic medium complete by formation of the corresponding hydrazones as a E-geometric isomers and s-trans/cis conformers with respect to the amide bond. In more severe conditions elimination of hydrazone fragments and retrocondensation of aminoazolophenylpropionyl residues in dihydroazolopyrimidinones have been observed.The composition and structure of the hydrazones synthesized for the first time have been proven by data of elemental analysis, infrared spectroscopy (IR), nuclear magnetic resonance on protones (1H NMR) and mass spectra.Virtual screening of the substances obtained carried out by using the PASS programme for 780 types of pharmacological action has shown that these compounds are advisable to test for the presence of their antibacterial and fungicidal properties. However, the experimental evaluation of the antimicrobial activity of N1-ylidene derivatives of 3-phenylpropanehydrazides performed on five museum strains of test cultures has revealed a weak activity against Staphylococcus aureus only in 3-(5-amΡ–no-1H-1,2,4-triazol-1-yl)-N1 benzilΡ–dene-3-phenylpropanehydrazide.Π Π΅Π°ΠΊΡ†ΠΈΠΈ 3-(5-Π°ΠΌΠΈΠ½ΠΎ-1Н-1,2,4-Ρ‚Ρ€ΠΈΠ°Π·ΠΎΠ»-1-ΠΈΠ»)- ΠΈ 3-(2-Π°ΠΌΠΈΠ½ΠΎ-1Н Π±Π΅Π½Π·ΠΎ[d]ΠΈΠΌΠΈΠ΄Π°Π·ΠΎΠ»-1-ΠΈΠ»)-3-Ρ„Π΅Π½ΠΈΠ»ΠΏΡ€ΠΎΠΏΠ°Π½Π³ΠΈΠ΄Ρ€Π°Π·ΠΈΠ΄ΠΎΠ² с ΠΊΠ°Ρ€Π±ΠΎΠ½ΠΈΠ»ΡŒΠ½Ρ‹ΠΌΠΈ элСктрофилами – Π°Ρ†Π΅Ρ‚ΠΈΠ»Π°Ρ†Π΅Ρ‚ΠΎΠ½ΠΎΠΌ, ароматичСскими ΠΈ гСтСроцикличСскими альдСгидами Π² спиртовой срСдС Π·Π°Π²Π΅Ρ€ΡˆΠ°ΡŽΡ‚ΡΡ ΠΎΠ±Ρ€Π°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΡΠΎΠΎΡ‚Π²Π΅Ρ‚ΡΡ‚Π²ΡƒΡŽΡ‰ΠΈΡ… Π³ΠΈΠ΄Ρ€Π°Π·ΠΎΠ½ΠΎΠ² Π² Π²ΠΈΠ΄Π΅ Π•-гСомСтричСских ΠΈΠ·ΠΎΠΌΠ΅Ρ€ΠΎΠ² ΠΈ s-trans/cis ΠΊΠΎΠ½Ρ„ΠΎΡ€ΠΌΠ΅Ρ€ΠΎΠ² ΠΏΠΎ ΠΎΡ‚Π½ΠΎΡˆΠ΅Π½ΠΈΡŽ ΠΊ Π°ΠΌΠΈΠ΄Π½ΠΎΠΉ связи. Π’ Π±ΠΎΠ»Π΅Π΅ ТСстких условиях происходит элиминированиС Π³ΠΈΠ΄Ρ€Π°Π·ΠΎΠ½Π½Ρ‹Ρ… Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚ΠΎΠ² ΠΈ рСтрокондСнсация Π°ΠΌΠΈΠ½ΠΎΠ°Π·ΠΎΠ»ΠΎΡ„Π΅Π½ΠΈΠ»ΠΏΡ€ΠΎΠΏΠΈΠΎΠ½ΠΈΠ»ΡŒΠ½Ρ‹Ρ… остатков Π² Π΄ΠΈΠ³ΠΈΠ΄Ρ€ΠΎΠ°Π·ΠΎΠ»ΠΎΠΏΠΈΡ€ΠΈΠΌΠΈΠ΄ΠΈΠ½ΠΎΠ½Ρ‹. Бостав ΠΈ строСниС Π²ΠΏΠ΅Ρ€Π²Ρ‹Π΅ синтСзированных Π³ΠΈΠ΄Ρ€Π°Π·ΠΎΠ½ΠΎΠ² Π΄ΠΎΠΊΠ°Π·Π°Π½ΠΎ с ΠΏΠΎΠΌΠΎΡ‰ΡŒΡŽ элСмСнтного Π°Π½Π°Π»ΠΈΠ·Π°, инфракрасной спСктроскопии (ИК), ядСрного ΠΌΠ°Π³Π½ΠΈΡ‚Π½ΠΎΠ³ΠΎ рСзонанса Π½Π° ΠΏΡ€ΠΎΡ‚ΠΎΠ½Π°Ρ… (ЯМР 1Н) ΠΈ масс-спСктромСтрии. Π’ΠΈΡ€Ρ‚ΡƒΠ°Π»ΡŒΠ½Ρ‹ΠΉ скрининг ΠΏΠΎΠ»ΡƒΡ‡Π΅Π½Π½Ρ‹Ρ… вСщСств, ΠΏΡ€ΠΎΠ²Π΅Π΄Π΅Π½Π½Ρ‹ΠΉ с использованиСм ΠΏΡ€ΠΎΠ³Ρ€Π°ΠΌΠΌΡ‹ PASS ΠΏΠΎ 780 Π²ΠΈΠ΄Π°ΠΌ фармакологичСского дСйствия, ΠΏΠΎΠΊΠ°Π·Π°Π», Ρ‡Ρ‚ΠΎ эти соСдинСния цСлСсообразно Ρ‚Π΅ΡΡ‚ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ Π½Π° Π½Π°Π»ΠΈΡ‡ΠΈΠ΅ Ρƒ Π½ΠΈΡ… Π°Π½Ρ‚ΠΈΠ±Π°ΠΊΡ‚Π΅Ρ€ΠΈΠ°Π»ΡŒΠ½Ρ‹Ρ… ΠΈ Ρ„ΡƒΠ½Π³ΠΈΡ†ΠΈΠ΄Π½Ρ‹Ρ… свойств. Однако ΡΠΊΡΠΏΠ΅Ρ€ΠΈΠΌΠ΅Π½Ρ‚Π°Π»ΡŒΠ½Π°Ρ ΠΎΡ†Π΅Π½ΠΊΠ° Π°Π½Ρ‚ΠΈΠΌΠΈΠΊΡ€ΠΎΠ±Π½ΠΎΠΉ активности N1-ΠΈΠ»ΠΈΠ΄Π΅Π½ΠΎΠ²Ρ‹Ρ… ΠΏΡ€ΠΎΠΈΠ·Π²ΠΎΠ΄Π½Ρ‹Ρ… 3-Ρ„Π΅Π½ΠΈΠ»ΠΏΡ€ΠΎΠΏΠ°Π½Π³ΠΈΠ΄Ρ€Π°Π·ΠΈΠ΄ΠΎΠ², провСдСнная Π½Π° пяти ΠΌΡƒΠ·Π΅ΠΉΠ½Ρ‹Ρ… ΡˆΡ‚Π°ΠΌΠΌΠ°Ρ… тСст-ΠΊΡƒΠ»ΡŒΡ‚ΡƒΡ€, ΠΎΠ±Π½Π°Ρ€ΡƒΠΆΠΈΠ»Π° ΡΠ»Π°Π±ΡƒΡŽ Π°ΠΊΡ‚ΠΈΠ²Π½ΠΎΡΡ‚ΡŒ ΠΎΡ‚Π½ΠΎΡΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎ Staphylococcus aureus Ρ‚ΠΎΠ»ΡŒΠΊΠΎ Ρƒ 3-(5-Π°ΠΌΠΈΠ½ΠΎ-1Н-1,2,4-Ρ‚Ρ€ΠΈΠ°Π·ΠΎΠ»-1-ΠΈΠ»)-N1-Π±Π΅Π½Π·ΠΈΠ»ΠΈΠ΄Π΅Π½-3 Ρ„Π΅Π½ΠΈΠ»ΠΏΡ€ΠΎΠΏΠ°Π½Π³ΠΈΠ΄Ρ€Π°Π·ΠΈΠ΄Π°.Π Π΅Π°ΠΊΡ†Ρ–Ρ— 3-(5-Π°ΠΌΡ–Π½ΠΎ-1Н-1,2,4-Ρ‚Ρ€ΠΈΠ°Π·ΠΎΠ»-1-Ρ–Π»)- Ρ‚Π° 3-(2-Π°ΠΌΡ–Π½ΠΎ-1Н-Π±Π΅Π½Π·ΠΎ[d]Ρ–ΠΌΡ–Π΄Π°Π·ΠΎΠ»-1-Ρ–Π»)-3-Ρ„Π΅Π½Ρ–Π»ΠΏΡ€ΠΎΠΏΠ°Π½Π³Ρ–Π΄Ρ€Π°Π·ΠΈΠ΄Ρ–Π² Π· ΠΊΠ°Ρ€Π±ΠΎΠ½Ρ–Π»ΡŒΠ½ΠΈΠΌΠΈ Π΅Π»Π΅ΠΊΡ‚Ρ€ΠΎΡ„Ρ–Π»Π°ΠΌΠΈ – Π°Ρ†Π΅Ρ‚ΠΈΠ»Π°Ρ†Π΅Ρ‚ΠΎΠ½ΠΎΠΌ, Π°Ρ€ΠΎΠΌΠ°Ρ‚ΠΈΡ‡Π½ΠΈΠΌΠΈ Ρ‚Π° Π³Π΅Ρ‚Π΅Ρ€ΠΎΡ†ΠΈΠΊΠ»Ρ–Ρ‡Π½ΠΈΠΌΠΈ Π°Π»ΡŒΠ΄Π΅Π³Ρ–Π΄Π°ΠΌΠΈ Ρƒ спиртовому сСрСдовищі Π·Π°Π²Π΅Ρ€ΡˆΡƒΡŽΡ‚ΡŒΡΡ утворСнням Π²Ρ–Π΄ΠΏΠΎΠ²Ρ–Π΄Π½ΠΈΡ… Π³Ρ–Π΄Ρ€Π°Π·ΠΎΠ½Ρ–Π² Ρƒ вигляді Π•-Π³Π΅ΠΎΠΌΠ΅Ρ‚Ρ€ΠΈΡ‡Π½ΠΈΡ… Ρ–Π·ΠΎΠΌΠ΅Ρ€Ρ–Π² Ρ– s-trans/cis ΠΊΠΎΠ½Ρ„ΠΎΡ€ΠΌΠ΅Ρ€Ρ–Π² ΠΏΠΎ Π²Ρ–Π΄Π½ΠΎΡˆΠ΅Π½Π½ΡŽ Π΄ΠΎ Π°ΠΌΡ–Π΄Π½ΠΎΠ³ΠΎ зв’язку. Π’ Π±Ρ–Π»ΡŒΡˆ Торстких ΡƒΠΌΠΎΠ²Π°Ρ… Π²Ρ–Π΄Π±ΡƒΠ²Π°Ρ”Ρ‚ΡŒΡΡ Слімінування Π³Ρ–Π΄Ρ€Π°Π·ΠΎΠ½Π½ΠΈΡ… Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚Ρ–Π² Ρ‚Π° рСтрокондСнсація Π°ΠΌΡ–Π½ΠΎΠ°Π·ΠΎΠ»ΠΎΡ„Π΅Π½Ρ–Π»ΠΏΡ€ΠΎΠΏΡ–ΠΎΠ½Ρ–Π»ΡŒΠ½ΠΈΡ… Π·Π°Π»ΠΈΡˆΠΊΡ–Π² Ρƒ Π΄ΠΈΠ³Ρ–Π΄Ρ€ΠΎΠ°Π·ΠΎΠ»ΠΎΠΏΡ–Ρ€ΠΈΠΌΡ–Π΄ΠΈΠ½ΠΎΠ½ΠΈ. Π‘ΠΊΠ»Π°Π΄ Ρ‚Π° Π±ΡƒΠ΄ΠΎΠ²Ρƒ Π²ΠΏΠ΅Ρ€ΡˆΠ΅ синтСзованих Π³Ρ–Π΄Ρ€Π°Π·ΠΎΠ½Ρ–Π² Π΄ΠΎΠ²Π΅Π΄Π΅Π½ΠΎ Π·Π° допомогою Π΅Π»Π΅ΠΌΠ΅Π½Ρ‚Π½ΠΎΠ³ΠΎ Π°Π½Π°Π»Ρ–Π·Ρƒ, Ρ–Π½Ρ„Ρ€Π°Ρ‡Π΅Ρ€Π²ΠΎΠ½ΠΎΡ— спСктроскопії (Π†Π§), ядСрного ΠΌΠ°Π³Π½Ρ–Ρ‚Π½ΠΎΠ³ΠΎ рСзонансу Π½Π° ΠΏΡ€ΠΎΡ‚ΠΎΠ½Π°Ρ… (ЯМР 1Н) Ρ‚Π° мас-спСктромСтрії. Π’Ρ–Ρ€Ρ‚ΡƒΠ°Π»ΡŒΠ½ΠΈΠΉ скринінг ΠΎΠ΄Π΅Ρ€ΠΆΠ°Π½ΠΈΡ… Ρ€Π΅Ρ‡ΠΎΠ²ΠΈΠ½, ΠΏΡ€ΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠΉ Ρ–Π· використанням ΠΏΡ€ΠΎΠ³Ρ€Π°ΠΌΠΈ PASS Π·Π° 780 Π²ΠΈΠ΄Π°ΠΌΠΈ Ρ„Π°Ρ€ΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³Ρ–Ρ‡Π½ΠΎΡ— Π΄Ρ–Ρ—, засвідчив, Ρ‰ΠΎ Ρ†Ρ– сполуки Π΄ΠΎΡ†Ρ–Π»ΡŒΠ½ΠΎ тСстувати Π½Π° Π½Π°ΡΠ²Π½Ρ–ΡΡ‚ΡŒ Ρƒ Π½ΠΈΡ… Π°Π½Ρ‚ΠΈΠ±Π°ΠΊΡ‚Π΅Ρ€Ρ–Π°Π»ΡŒΠ½ΠΈΡ… Ρ‚Π° Ρ„ΡƒΠ½Π³Ρ–Ρ†ΠΈΠ΄Π½ΠΈΡ… властивостСй. Однак Π΅ΠΊΡΠΏΠ΅Ρ€ΠΈΠΌΠ΅Π½Ρ‚Π°Π»ΡŒΠ½Π° ΠΎΡ†Ρ–Π½ΠΊΠ° Π°Π½Ρ‚ΠΈΠΌΡ–ΠΊΡ€ΠΎΠ±Π½ΠΎΡ— активності N1-Ρ–Π»Ρ–Π΄Π΅Π½ΠΎΠ²ΠΈΡ… ΠΏΠΎΡ…Ρ–Π΄Π½ΠΈΡ… 3-Ρ„Π΅Π½Ρ–Π»ΠΏΡ€ΠΎΠΏΠ°Π½Π³Ρ–Π΄Ρ€Π°Π·ΠΈΠ΄Ρ–Π², ΠΏΡ€ΠΎΠ²Π΅Π΄Π΅Π½Π° Π½Π° п’яти ΠΌΡƒΠ·Π΅ΠΉΠ½ΠΈΡ… ΡˆΡ‚Π°ΠΌΠ°Ρ… тСст-ΠΊΡƒΠ»ΡŒΡ‚ΡƒΡ€, виявила слабку Π°ΠΊΡ‚ΠΈΠ²Π½Ρ–ΡΡ‚ΡŒ відносно Staphylococcus aureus лишС Ρƒ 3-(5-Π°ΠΌΡ–Π½ΠΎ-1Н-1,2,4-Ρ‚Ρ€ΠΈΠ°Π·ΠΎΠ»-1-Ρ–Π»)-N1-Π±Π΅Π½Π·ΠΈΠ»Ρ–Π΄Π΅Π½-3-Ρ„Π΅Π½Ρ–Π»ΠΏΡ€ΠΎΠΏΠ°Π½Π³Ρ–Π΄Ρ€Π°Π·ΠΈΠ΄Ρƒ

    Π”ΠΎΠΌΡ–Π½ΠΎ-Ρ€Π΅Π°ΠΊΡ†Ρ–Ρ— Ρ–Π·Π°Ρ‚ΠΈΠ½Ρ–Π² Π· 5-Π°ΠΌΡ–Π½ΠΎΠΏΡ–Ρ€Π°Π·ΠΎΠ»Π°ΠΌΠΈ Ρ‚Π° 2,2-Π΄ΠΈΠΌΠ΅Ρ‚ΠΈΠ»-1,3-діоксан-4,6-Π΄Ρ–ΠΎΠ½ΠΎΠΌ

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    Aim. To determine the direction of the interaction of isatins with 5-amino-pyrazoles and 2,2-dimethyl-1,3-dioxane-4,6-dione under different conditions.Results and discussion. The domino-reactions of isatins, 5-aminopyrazoles and 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum’s acid) in the alcoholic medium are completed by formation of a mixture of pyrazolo[3,4-b]pyridine-4-spiroindolinones and 3-(5-aminopyrazol-3-yl)-3-hydroxy-2-oxindolines with the predominant content of spiro compounds. 3-(5-Aminopyrazol-4-yl)-3-hydroxy-2-oxindolines may turn into pyrazolo[3,4-b]pyridine-4-spiroindolinones very slowly only as a result of retrograde fragmentation to isatin and aminopyrazole in the presence of Meldrum’s acid.Experimental part. The mixtures of pyrazolo[3,4-b]pyridine-4-spiroindolinones and 3-(5-aminopyrazol-3-yl)-3-hydroxy-2-oxindolines separated by crystallization were obtained by boiling in methanol of the equimolar quantity of isatins, 5-aminopyrazoles and Meldrum’s acids. The yield for spiro compounds is 26-82 %, and for 3-(5-aminopyrazole-3-yl)-3-hydroxy-2-oxindolines it is 5-23 %. The transformation of the latter into the spiro compound in the presence of Meldrum’s acid occurs with prolonged boiling in the alcoholic medium and is accompanied with extremely low yields. The structure of all compounds synthesized has been proven by 1H NMR, mass spectra and elemental analysis.Conclusions. It has been found that in the three-component reactions of isatins, 5-aminopyrazoles and 2,2-dimethyl-1,3-dioxane-4,6-dione there are two competing directions of the interaction of isatin with nucleophiles. One of them is the nucleophilic addition of the C4 reaction center of aminopyrazole to the carbonyl group of isatin, which results in 3-(5-aminopyrazol-4-yl)-3-hydroxy-2-oxidolines. Another one is the Knoevenagel condensation of isatin with dioxane-4,6-dione – a domino process that starts formation of the predominant reaction products – pyrazolo[3,4-b]pyridine-4-spiroindolinones.ЦСль Ρ€Π°Π±ΠΎΡ‚Ρ‹ – ΡƒΡΡ‚Π°Π½ΠΎΠ²ΠΈΡ‚ΡŒ Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½Π½ΠΎΡΡ‚ΡŒ взаимодСйствия ΠΈΠ·Π°Ρ‚ΠΈΠ½ΠΎΠ² с 5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡ€Π°Π·ΠΎΠ»Π°ΠΌΠΈ ΠΈ 2,2-Π΄ΠΈΠΌΠ΅Ρ‚ΠΈΠ»-1,3-диоксан-4,6-Π΄ΠΈΠΎΠ½ΠΎΠΌ Π² Ρ€Π°Π·Π½Ρ‹Ρ… условиях.Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹ ΠΈ ΠΈΡ… обсуТдСниС. Π”ΠΎΠΌΠΈΠ½ΠΎ-Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ ΠΈΠ·Π°Ρ‚ΠΈΠ½ΠΎΠ², 5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡ€Π°Π·ΠΎΠ»ΠΎΠ² ΠΈ 2,2-Π΄ΠΈΠΌΠ΅Ρ‚ΠΈΠ»-1,3-диоксан-4,6-Π΄ΠΈΠΎΠ½Π° (кислоты ΠœΠ΅Π»ΡŒΠ΄Ρ€ΡƒΠΌΠ°) Π² спиртовой срСдС Π·Π°Π²Π΅Ρ€ΡˆΠ°ΡŽΡ‚ΡΡ ΠΎΠ±Ρ€Π°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ смСсСй ΠΏΠΈΡ€Π°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΠΈΡ€ΠΈΠ΄ΠΈΠ½-4-спироиндолинонов ΠΈ 3-(5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡ€Π°Π·ΠΎΠ»-3-ΠΈΠ»)-3-гидрокси-2-оксиндолинов с ΠΏΡ€Π΅ΠΎΠ±Π»Π°Π΄Π°ΡŽΡ‰ΠΈΠΌ содСрТаниСм спиро-соСдинСний. 3-(5-Аминопиразол-4-ΠΈΠ»)-3-гидрокси-2-оксиндолины лишь Π² Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Π΅ рСтрораспада Π½Π° исходныС ΠΈΠ·Π°Ρ‚ΠΈΠ½ ΠΈ Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡ€Π°Π·ΠΎΠ» Π² присутствии кислоты ΠœΠ΅Π»ΡŒΠ΄Ρ€ΡƒΠΌΠ° ΠΌΠΎΠ³ΡƒΡ‚ ΠΎΡ‡Π΅Π½ΡŒ ΠΌΠ΅Π΄Π»Π΅Π½Π½ΠΎ с Π½ΠΈΠ·ΠΊΠΈΠΌΠΈ Π²Ρ‹Ρ…ΠΎΠ΄Π°ΠΌΠΈ ΠΏΡ€Π΅Π²Ρ€Π°Ρ‰Π°Ρ‚ΡŒΡΡ Π² ΠΏΠΈΡ€Π°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΠΈΡ€ΠΈΠ΄ΠΈΠ½-4-спироиндолиноны.Π­ΠΊΡΠΏΠ΅Ρ€ΠΈΠΌΠ΅Π½Ρ‚Π°Π»ΡŒΠ½Π°Ρ Ρ‡Π°ΡΡ‚ΡŒ. ΠšΠΈΠΏΡΡ‡Π΅Π½ΠΈΠ΅ΠΌ Π² ΠΌΠ΅Ρ‚Π°Π½ΠΎΠ»Π΅ ΡΠΊΠ²ΠΈΠΌΠΎΠ»ΡŒΠ½Ρ‹Ρ… количСств ΠΈΠ·Π°Ρ‚ΠΈΠ½ΠΎΠ², 5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡ€Π°Π·ΠΎΠ»ΠΎΠ² ΠΈ кислоты ΠœΠ΅Π»ΡŒΠ΄Ρ€ΡƒΠΌΠ° ΠΏΠΎΠ»ΡƒΡ‡Π΅Π½Ρ‹ смСси ΠΏΠΈΡ€Π°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΠΈΡ€ΠΈΠ΄ΠΈΠ½-4-спироиндолинонов ΠΈ 3-(5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡ€Π°Π·ΠΎΠ»-3-ΠΈΠ»)-3-гидрокси-2-оксиндолинов, ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Π΅ Ρ€Π°Π·Π΄Π΅Π»Π΅Π½Ρ‹ кристаллизациСй. Π’Ρ‹Ρ…ΠΎΠ΄ спиро-соСдинСний составляСт 26-82 %, Π° 3-(5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡ€Π°Π·ΠΎΠ»-3-ΠΈΠ»)-3-гидрокси-2-оксиндолинов – 5-23 %. ΠŸΡ€Π΅Π²Ρ€Π°Ρ‰Π΅Π½ΠΈΠ΅ послСдних Π² присутствии кислоты ΠœΠ΅Π»ΡŒΠ΄Ρ€ΡƒΠΌΠ° Π² спиро-соСдинСния происходит ΠΏΡ€ΠΈ Π΄Π»ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΠΌ кипячСнии Π² спиртовой срСдС ΠΈ сопровоТдаСтся ΠΊΡ€Π°ΠΉΠ½Π΅ Π½ΠΈΠ·ΠΊΠΈΠΌΠΈ Π²Ρ‹Ρ…ΠΎΠ΄Π°ΠΌΠΈ. Π‘Ρ‚Ρ€ΠΎΠ΅Π½ΠΈΠ΅ ΠΈ состав всСх синтСзированных соСдинСний Π΄ΠΎΠΊΠ°Π·Π°Π½Ρ‹ Π΄Π°Π½Π½Ρ‹ΠΌΠΈ ЯМР 1Н, масс-спСктров ΠΈ элСмСнтным Π°Π½Π°Π»ΠΈΠ·ΠΎΠΌ.Π’Ρ‹Π²ΠΎΠ΄Ρ‹. УстановлСно, Ρ‡Ρ‚ΠΎ Π² Ρ‚Ρ€Π΅Ρ…ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½Ρ‚Π½Ρ‹Ρ… рСакциях ΠΈΠ·Π°Ρ‚ΠΈΠ½ΠΎΠ², 5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡ€Π°Π·ΠΎΠ»ΠΎΠ² ΠΈ 2,2-Π΄ΠΈΠΌΠ΅Ρ‚ΠΈΠ»-1,3-диоксан-4,6-Π΄ΠΈΠΎΠ½Π° Ρ€Π΅Π°Π»ΠΈΠ·ΡƒΡŽΡ‚ΡΡ Π΄Π²Π° ΠΊΠΎΠ½ΠΊΡƒΡ€ΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… направлСния взаимодСйствия ΠΈΠ·Π°Ρ‚ΠΈΠ½Π° с Π½ΡƒΠΊΠ»Π΅ΠΎΡ„ΠΈΠ»Π°ΠΌΠΈ. Одно ΠΈΠ· Π½ΠΈΡ… – Π½ΡƒΠΊΠ»Π΅ΠΎΡ„ΠΈΠ»ΡŒΠ½ΠΎΠ΅ присоСдинСниС Π‘4 Ρ€Π΅Π°ΠΊΡ†ΠΈΠΎΠ½Π½ΠΎΠ³ΠΎ Ρ†Π΅Π½Ρ‚Ρ€Π° Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡ€Π°Π·ΠΎΠ»Π° ΠΊ ΠΊΠ°Ρ€Π±ΠΎΠ½ΠΈΠ»ΡŒΠ½ΠΎΠΉ Π³Ρ€ΡƒΠΏΠΏΠ΅ ΠΈΠ·Π°Ρ‚ΠΈΠ½Π° ΠΏΡ€ΠΈΠ²ΠΎΠ΄ΠΈΡ‚ ΠΊ 3-(5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡ€Π°Π·ΠΎΠ»-4-ΠΈΠ»)-3-гидрокси-2-оксиндолинам. А Π²Ρ‚ΠΎΡ€ΠΎΠ΅ – кондСнсация ΠΈΠ·Π°Ρ‚ΠΈΠ½Π° с диоксан-4,6-Π΄ΠΈΠΎΠ½ΠΎΠΌ ΠΏΠΎ КнСвСнагСлю ΠΈΠ½ΠΈΡ†ΠΈΠΈΡ€ΡƒΠ΅Ρ‚ Π΄ΠΎΠΌΠΈΠ½ΠΎ-процСсс, ΠΊΠΎΡ‚ΠΎΡ€Ρ‹ΠΉ Π·Π°Π²Π΅Ρ€ΡˆΠ°Π΅Ρ‚ΡΡ ΠΎΠ±Ρ€Π°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ основных ΠΏΡ€ΠΎΠ΄ΡƒΠΊΡ‚ΠΎΠ² Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ – ΠΏΠΈΡ€Π°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΠΈΡ€ΠΈΠ΄ΠΈΠ½-4-спироиндолинонов.ΠœΠ΅Ρ‚Π° Ρ€ΠΎΠ±ΠΎΡ‚ΠΈ – встановити Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½Ρ–ΡΡ‚ΡŒ Π²Π·Π°Ρ”ΠΌΠΎΠ΄Ρ–Ρ— Ρ–Π·Π°Ρ‚ΠΈΠ½Ρ–Π² Π· 5-Π°ΠΌΡ–Π½ΠΎΠΏΡ–Ρ€Π°Π·ΠΎΠ»Π°ΠΌΠΈ Ρ‚Π° 2,2-Π΄ΠΈΠΌΠ΅Ρ‚ΠΈΠ»-1,3-діоксан-4,6-Π΄Ρ–ΠΎΠ½ΠΎΠΌ Ρƒ Ρ€Ρ–Π·Π½ΠΈΡ… ΡƒΠΌΠΎΠ²Π°Ρ….Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚ΠΈ Ρ‚Π° Ρ—Ρ… обговорСння. Π”ΠΎΠΌΡ–Π½ΠΎ-Ρ€Π΅Π°ΠΊΡ†Ρ–Ρ— Ρ–Π·Π°Ρ‚ΠΈΠ½Ρ–Π², 5-Π°ΠΌΡ–Π½ΠΎΠΏΡ–Ρ€Π°Π·ΠΎΠ»Ρ–Π² Ρ‚Π° 2,2-Π΄ΠΈΠΌΠ΅Ρ‚ΠΈΠ»-1,3-діоксан-4,6-Π΄Ρ–ΠΎΠ½Ρƒ (кислоти ΠœΠ΅Π»ΡŒΠ΄Ρ€ΡƒΠΌΠ°) Ρƒ спиртовому сСрСдовищі Π·Π°Π²Π΅Ρ€ΡˆΡƒΡŽΡ‚ΡŒΡΡ утворСнням ΡΡƒΠΌΡ–ΡˆΡ– ΠΏΡ–Ρ€Π°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΡ–Ρ€ΠΈΠ΄ΠΈΠ½-4-спіроіндолінонів Ρ‚Π° 3-(5-Π°ΠΌΡ–Π½ΠΎΠΏΡ–Ρ€Π°Π·ΠΎΠ»-3-Ρ–Π»)-3-гідрокси-2-оксіндолінів Π· ΠΏΠ΅Ρ€Π΅Π²Π°ΠΆΠ½ΠΈΠΌ вмістом спіро-сполук. 3-(5-Амінопіразол-4-Ρ–Π»)-3-гідрокси-2-оксіндоліни лишС Π² Ρ€Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ– Ρ€Π΅Ρ‚Ρ€ΠΎΡ€ΠΎΠ·ΠΏΠ°Π΄Ρƒ Π½Π° Π²ΠΈΡ…Ρ–Π΄Π½Ρ– Ρ–Π·Π°Ρ‚ΠΈΠ½ Ρ‚Π° Π°ΠΌΡ–Π½ΠΎΠΏΡ–Ρ€Π°Π·ΠΎΠ» Ρƒ присутності кислоти ΠœΠ΅Π»ΡŒΠ΄Ρ€ΡƒΠΌΠ° ΠΌΠΎΠΆΡƒΡ‚ΡŒ Π΄ΡƒΠΆΠ΅ ΠΏΠΎΠ²Ρ–Π»ΡŒΠ½ΠΎ Π· низькими Π²ΠΈΡ…ΠΎΠ΄Π°ΠΌΠΈ ΠΏΠ΅Ρ€Π΅Ρ‚Π²ΠΎΡ€ΡŽΠ²Π°Ρ‚ΠΈΡΡ Π½Π° ΠΏΡ–Ρ€Π°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΡ–Ρ€ΠΈΠ΄ΠΈΠ½-4-спіроіндолінони.Π•ΠΊΡΠΏΠ΅Ρ€ΠΈΠΌΠ΅Π½Ρ‚Π°Π»ΡŒΠ½Π° частина. ΠšΠΈΠΏβ€™ΡΡ‚Ρ–Π½Π½ΡΠΌ Ρƒ ΠΌΠ΅Ρ‚Π°Π½ΠΎΠ»Ρ– Π΅ΠΊΠ²Ρ–ΠΌΠΎΠ»ΡŒΠ½ΠΈΡ… ΠΊΡ–Π»ΡŒΠΊΠΎΡΡ‚Π΅ΠΉ Ρ–Π·Π°Ρ‚ΠΈΠ½Ρ–Π², 5-Π°ΠΌΡ–Π½ΠΎΠΏΡ–Ρ€Π°Π·ΠΎΠ»Ρ–Π² Ρ‚Π° кислоти ΠœΠ΅Π»ΡŒΠ΄Ρ€ΡƒΠΌΠ° ΠΎΠ΄Π΅Ρ€ΠΆΠ°Π½ΠΎ ΡΡƒΠΌΡ–ΡˆΡ– ΠΏΡ–Ρ€Π°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΡ–Ρ€ΠΈΠ΄ΠΈΠ½-4-спіроіндолінонів Ρ‚Π° 3-(5-Π°ΠΌΡ–Π½ΠΎΠΏΡ–Ρ€Π°Π·ΠΎΠ»-3-Ρ–Π»)-3-гідрокси-2-оксіндолінів, які Ρ€ΠΎΠ·Π΄Ρ–Π»Π΅Π½Ρ– ΠΊΡ€ΠΈΡΡ‚Π°Π»Ρ–Π·Π°Ρ†Ρ–Ρ”ΡŽ. Π’ΠΈΡ…Ρ–Π΄ спіро-сполук складає 26-82 %, Π° 3-(5-Π°ΠΌΡ–Π½ΠΎΠΏΡ–Ρ€Π°Π·ΠΎΠ»-3-Ρ–Π»)-3-гідрокси-2-оксіндолінів – 5-23 %. ΠŸΠ΅Ρ€Π΅Ρ‚Π²ΠΎΡ€Π΅Π½Π½Ρ останніх Ρƒ присутності кислоти ΠœΠ΅Π»ΡŒΠ΄Ρ€ΡƒΠΌΠ° Π½Π° спіро-сполуки Π²Ρ–Π΄Π±ΡƒΠ²Π°Ρ”Ρ‚ΡŒΡΡ ΠΏΡ€ΠΈ Ρ‚Ρ€ΠΈΠ²Π°Π»ΠΎΠΌΡƒ кип’ятінні Ρƒ спиртовому сСрСдовищі Ρ– ΡΡƒΠΏΡ€ΠΎΠ²ΠΎΠ΄ΠΆΡƒΡ”Ρ‚ΡŒΡΡ Π²ΠΊΡ€Π°ΠΉ низькими Π²ΠΈΡ…ΠΎΠ΄Π°ΠΌΠΈ. Π‘Ρ‚Ρ€ΡƒΠΊΡ‚ΡƒΡ€Ρƒ Ρ– склад усіх синтСзованих сполук Π΄ΠΎΠ²Π΅Π΄Π΅Π½ΠΎ Π΄Π°Π½ΠΈΠΌΠΈ ЯМР 1Н, мас-спСктрів Ρ– Π΅Π»Π΅ΠΌΠ΅Π½Ρ‚Π½ΠΈΠΌ Π°Π½Π°Π»Ρ–Π·ΠΎΠΌ.Висновки. ВстановлСно, Ρ‰ΠΎ Ρƒ Ρ‚Ρ€ΠΈΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½Ρ‚Π½ΠΈΡ… рСакціях Ρ–Π·Π°Ρ‚ΠΈΠ½Ρ–Π², 5-Π°ΠΌΡ–Π½ΠΎΠΏΡ–Ρ€Π°Π·ΠΎΠ»Ρ–Π² Ρ– 2,2-Π΄ΠΈΠΌΠ΅Ρ‚ΠΈΠ»-1,3-діоксан-4,6-Π΄Ρ–ΠΎΠ½Ρƒ Ρ€Π΅Π°Π»Ρ–Π·ΡƒΡŽΡ‚ΡŒΡΡ Π΄Π²Π° ΠΊΠΎΠ½ΠΊΡƒΡ€ΡƒΡŽΡ‡ΠΈΡ… напрямки Π²Π·Π°Ρ”ΠΌΠΎΠ΄Ρ–Ρ— Ρ–Π·Π°Ρ‚ΠΈΠ½Ρƒ Π· Π½ΡƒΠΊΠ»Π΅ΠΎΡ„Ρ–Π»Π°ΠΌΠΈ. Один Π· Π½ΠΈΡ… – Π½ΡƒΠΊΠ»Π΅ΠΎΡ„Ρ–Π»ΡŒΠ½Π΅ приєднання Π‘4 Ρ€Π΅Π°ΠΊΡ†Ρ–ΠΉΠ½ΠΎΠ³ΠΎ Ρ†Π΅Π½Ρ‚Ρ€Π° Π°ΠΌΡ–Π½ΠΎΠΏΡ–Ρ€Π°Π·ΠΎΠ»Ρƒ Π΄ΠΎ ΠΊΠ°Ρ€Π±ΠΎΠ½Ρ–Π»ΡŒΠ½ΠΎΡ— Π³Ρ€ΡƒΠΏΠΈ Ρ–Π·Π°Ρ‚ΠΈΠ½Ρƒ ΠΏΡ€ΠΈΠ²ΠΎΠ΄ΠΈΡ‚ΡŒ Π΄ΠΎ 3-(5-Π°ΠΌΡ–Π½ΠΎΠΏΡ–Ρ€Π°Π·ΠΎΠ»-4-Ρ–Π»)-3-гідрокси-2-оксіндолінів. А Ρ–Π½ΡˆΠΈΠΉ – кондСнсація Ρ–Π·Π°Ρ‚ΠΈΠ½Ρƒ Π· діоксан-4,6-Π΄Ρ–ΠΎΠ½ΠΎΠΌ Π·Π° КньовСнагСлСм Π·Π°ΠΏΠΎΡ‡Π°Ρ‚ΠΊΠΎΠ²ΡƒΡ” Π΄ΠΎΠΌΡ–Π½ΠΎ-процСс, який Π·Π°Π²Π΅Ρ€ΡˆΡƒΡ”Ρ‚ΡŒΡΡ утворСнням ΠΏΠ΅Ρ€Π΅Π²Π°ΠΆΠ½ΠΈΡ… ΠΏΡ€ΠΎΠ΄ΡƒΠΊΡ‚Ρ–Π² Ρ€Π΅Π°ΠΊΡ†Ρ–Ρ— – ΠΏΡ–Ρ€Π°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΡ–Ρ€ΠΈΠ΄ΠΈΠ½-4-спіроіндолінонів

    Π”ΠΎΠΌΡ–Π½ΠΎ-Ρ€Π΅Π°ΠΊΡ†Ρ–Ρ— 3-ΠΌΠ΅Ρ‚ΠΈΠ»-5-Π°ΠΌΡ–Π½ΠΎΠΏΡ–Ρ€Π°Π·ΠΎΠ»Ρƒ Π· 1-Ρ„Π΅Π½Ρ–Π»-3-(4-алкоксифСніл)ΠΏΡ–Ρ€Π°Π·ΠΎΠ»-4-ΠΊΠ°Ρ€Π±Π°Π»ΡŒΠ΄Π΅Π³Ρ–Π΄Π°ΠΌΠΈ Ρ‚Π° 2,2-Π΄ΠΈΠΌΠ΅Ρ‚ΠΈΠ»-1,3-діоксан-4,6-Π΄Ρ–ΠΎΠ½ΠΎΠΌ

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    Aim. To synthesize 1-phenyl-3-(4-alkoxyphenyl)pyrazole-4-carbaldehydes and determine the direction of their interaction in the three-component condensation with 3-methyl-5-aminopyrazole and 2,2-dimethyl-1,3-dioxane-4,6-dione.Results and discussion. A series of 1-phenyl-3-(4-alkoxyphenyl)pyrazole-4-carbaldehydes was synthesized from arylhydrazone by the Vilsmeier–Haak reaction. The domino-reactions of these aldehydes with 3-methyl-5-aminopyrazole and 2,2-dimethyl-1,3-dioxane-4,6-dione lead to pyrazolo[3,4-b]pyridone systems.Experimental part. The synthesis of 1-phenyl-3-(4-alkoxyphenyl)pyrazole-4-carbaldehyde was carried out by formylation of arylhydrazones under the conditions of the Vilsmeier–Haack reaction with the yield of 55 – 88 %. Refluxing in 2-propanol equimolar amounts of these aldehydes, 3-methyl-5-aminopyrazole and 2,2-dimethyl-1,3-dioxane-4,6-dione gave 3-methyl-4-(1',3'-diarylpyrazol-4'-yl)tetrahydropyrazolo[3,4-b]pyridin-6-ones with the yield of 48 – 75 %. The structure and composition of all substances synthesized were proven by 1H NMR, IR-spectra and elemental analysis.Conclusions. It has been found that the reactions of 1,3-diaryl substituted pyrazole-4-carbaldehydes with 3-methyl-5-aminopyrazole and 2,2-dimethyl-1,3-dioxane-4,6-dione are regioselective and lead to the formation of pyrazolo[3,4-b]pyridone systems. This orientation of the process corresponds to the interaction of the Ξ²-carbon atom of the probable intermediate, which is formed at the first stage of the reaction from dioxandione and aldehyde, with the carbon nucleophilic center in the aminoazole molecule, and then the exocyclic amino group in the heterylamine attacks the C=O group in the dioxane-4,6-dione fragment.ЦСль. Π‘ΠΈΠ½Ρ‚Π΅Π·ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ 1-Ρ„Π΅Π½ΠΈΠ»-3-(4-алкоксифСнил)ΠΏΠΈΡ€Π°Π·ΠΎΠ»-4-ΠΊΠ°Ρ€Π±Π°Π»ΡŒΠ΄Π΅Π³ΠΈΠ΄Ρ‹ ΠΈ ΡƒΡΡ‚Π°Π½ΠΎΠ²ΠΈΡ‚ΡŒ Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½Π½ΠΎΡΡ‚ΡŒ ΠΈΡ… взаимодСйствия Π² Ρ‚Ρ€Π΅Ρ…ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½Ρ‚Π½ΠΎΠΉ кондСнсации с 3-ΠΌΠ΅Ρ‚ΠΈΠ»-5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡ€Π°Π·ΠΎΠ»ΠΎΠΌ ΠΈ 2,2-Π΄ΠΈΠΌΠ΅Ρ‚ΠΈΠ»-1,3-диоксан-4,6-Π΄ΠΈΠΎΠ½ΠΎΠΌ.Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹ ΠΈ ΠΈΡ… обсуТдСниС. Π€ΠΎΡ€ΠΌΠΈΠ»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π°Ρ€ΠΈΠ»Π³ΠΈΠ΄Ρ€Π°Π·ΠΎΠ½ΠΎΠ² ΠΏΠΎ Π’ΠΈΠ»ΡŒΡΠΌΠ΅ΠΉΠ΅Ρ€Ρƒβ€“Π₯Π°Π°ΠΊΡƒ синтСзирован ряд 1-Ρ„Π΅Π½ΠΈΠ»-3-(4-алкоксифСнил)ΠΏΠΈΡ€Π°Π·ΠΎΠ»-4-ΠΊΠ°Ρ€Π±Π°Π»ΡŒΠ΄Π΅Π³ΠΈΠ΄ΠΎΠ². Π”ΠΎΠΌΠΈΠ½ΠΎ-Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ этих альдСгидов с 3-ΠΌΠ΅Ρ‚ΠΈΠ»-5-Π°ΠΌΠΈΠ½ΠΎΒ­ΠΏΠΈΡ€Π°Π·ΠΎΠ»ΠΎΠΌ ΠΈ 2,2-Π΄ΠΈΠΌΠ΅Ρ‚ΠΈΠ»-1,3-диоксан-4,6-Π΄ΠΈΠΎΠ½ΠΎΠΌ Π·Π°Π²Π΅Ρ€ΡˆΠ°ΡŽΡ‚ΡΡ ΠΎΠ±Ρ€Π°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΏΠΈΡ€Π°Π·ΠΎΠ»ΠΎ[3,4-b]-ΠΏΠΈΡ€ΠΈΠ΄ΠΎΠ½ΠΎΠ²Ρ‹Ρ… систСм.Π­ΠΊΡΠΏΠ΅Ρ€ΠΈΠΌΠ΅Π½Ρ‚Π°Π»ΡŒΠ½Π°Ρ Ρ‡Π°ΡΡ‚ΡŒ. Π‘ΠΈΠ½Ρ‚Π΅Π· 1-Ρ„Π΅Π½ΠΈΠ»-3-(4-алкоксифСнил)Β­ΠΏΠΈΡ€Π°Β­Π·ΠΎΠ»-4-ΠΊΠ°Ρ€Π±Π°Π»ΡŒΠ΄Π΅Π³ΠΈΠ΄ΠΎΠ² осущСствлСн  Ρ„ΠΎΡ€ΠΌΠΈΠ»ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π°Ρ€ΠΈΠ»Π³ΠΈΠ΄Ρ€Π°Π·ΠΎΠ½ΠΎΠ² Π² условиях Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ Π’ΠΈΠ»ΡŒΡΠΌΠ΅ΠΉΠ΅Ρ€Π°β€“Π₯Π°Π°ΠΊΠ° с Π²Ρ‹Ρ…ΠΎΠ΄ΠΎΠΌ 55 – 88 %. ΠšΠΈΠΏΡΡ‡Π΅Π½ΠΈΠ΅ΠΌ Π² 2-ΠΏΡ€ΠΎΠΏΠ°Π½ΠΎΠ»Π΅ эквимолярных количСств этих альдСгидов, 3-ΠΌΠ΅Ρ‚ΠΈΠ»-5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡ€Π°Π·ΠΎΠ»Π° ΠΈ 2,2-Π΄ΠΈΠΌΠ΅Ρ‚ΠΈΠ»-1,3-диоксан-4,6-Π΄ΠΈΠΎΠ½Π° ΠΏΠΎΠ»ΡƒΡ‡Π΅Π½Ρ‹ 3-ΠΌΠ΅Ρ‚ΠΈΠ»-4-(1β€²,3β€²-Π΄ΠΈΠ°Ρ€ΠΈΠ»ΠΏΠΈΡ€Π°Π·ΠΎΠ»-4β€²-ΠΈΠ»)Ρ‚Π΅Ρ‚Ρ€Π°Π³ΠΈΠ΄Ρ€ΠΎΠΏΠΈΡ€Π°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΠΈΡ€ΠΈΠ΄ΠΈΠ½-6-ΠΎΠ½Ρ‹. Π’Ρ‹Ρ…ΠΎΠ΄ Ρ†Π΅Π»Π΅Π²Ρ‹Ρ… соСдинСний – 48 – 75 %. Π‘Ρ‚Ρ€ΠΎΠ΅Π½ΠΈΠ΅ ΠΈ состав всСх синтСзированных вСщСств Π΄ΠΎΠΊΠ°Π·Π°Π½Ρ‹ Π΄Π°Π½Π½Ρ‹ΠΌΠΈ 1Н ЯМР-, ИК-спСктров ΠΈ элСмСнтным Π°Π½Π°Π»ΠΈΠ·ΠΎΠΌ.Π’Ρ‹Π²ΠΎΠ΄Ρ‹. УстановлСно, Ρ‡Ρ‚ΠΎ Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ 1,3-Π΄ΠΈΠ°Ρ€ΠΈΠ»Π·Π°ΠΌΠ΅Ρ‰Π΅Π½Π½Ρ‹Ρ… ΠΏΠΈΡ€Π°Π·ΠΎΠ»-4-ΠΊΠ°Ρ€Π±Π°Π»ΡŒΠ΄Π΅Π³ΠΈΠ΄ΠΎΠ² с 3-ΠΌΠ΅Ρ‚ΠΈΠ»- 5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡ€Π°Π·ΠΎΠ»ΠΎΠΌ ΠΈ 2,2‑димСтил-1,3-диоксан-4,6-Π΄ΠΈΠΎΠ½ΠΎΠΌ рСгиосСлСктивны ΠΈ Π·Π°Π²Π΅Ρ€ΡˆΠ°ΡŽΡ‚ΡΡ ΠΎΠ±Ρ€Π°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ 3,4-ΠΏΠΈΡ€Π°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΠΈΡ€ΠΈΠ΄ΠΎΠ½ΠΎΠ²Ρ‹Ρ… систСм. Вакая Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½Π½ΠΎΡΡ‚ΡŒ процСсса ΠΎΡ‚Π²Π΅Ρ‡Π°Π΅Ρ‚ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡ‚Π²ΠΈΡŽ Ξ²-ΡƒΠ³Π»Π΅Ρ€ΠΎΠ΄Π½ΠΎΠ³ΠΎ Π°Ρ‚ΠΎΠΌΠ° Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠ³ΠΎ ΠΈΠ½Ρ‚Π΅Ρ€ΠΌΠ΅Π΄ΠΈΠ°Ρ‚Π°, ΠΎΠ±Ρ€Π°Π·ΡƒΡŽΡ‰Π΅Π³ΠΎΡΡ Π½Π° ΠΏΠ΅Ρ€Π²ΠΎΠΉ стадии ΠΈΠ· диоксандиона ΠΈ альдСгида, с ΡƒΠ³Π»Π΅Ρ€ΠΎΠ΄Π½Ρ‹ΠΌ Π½ΡƒΠΊΠ»Π΅ΠΎΡ„ΠΈΠ»ΡŒΠ½Ρ‹ΠΌ Ρ†Π΅Π½Ρ‚Ρ€ΠΎΠΌ Π² ΠΌΠΎΠ»Π΅ΠΊΡƒΠ»Π΅ Π°ΠΌΠΈΠ½ΠΎΠ°Π·ΠΎΠ»Π°, Π° Π°Ρ‚ΠΎΠΌΠ° ΡƒΠ³Π»Π΅Ρ€ΠΎΠ΄Π° Π‘=О Π³Ρ€ΡƒΠΏΠΏΡ‹ диоксан-4,6-Π΄ΠΈΠΎΠ½Π° – с экзоцикличСской Π°ΠΌΠΈΠ½ΠΎΠ³Ρ€ΡƒΠΏΠΏΠΎΠΉ Π³Π΅Ρ‚Π΅Ρ€ΠΈΠ»Π°ΠΌΠΈΠ½Π°.Β Received: 13.01.2019Revised: 31.01.2020Accepted: 27.02.2020ΠœΠ΅Ρ‚Π°. Π‘ΠΈΠ½Ρ‚Π΅Π·ΡƒΠ²Π°Ρ‚ΠΈ 1-Ρ„Π΅Π½Ρ–Π»-3-(4-алкоксифСніл)ΠΏΡ–Ρ€Π°Π·ΠΎΠ»-4-ΠΊΠ°Ρ€Π±Π°Π»ΡŒΠ΄Π΅Π³Ρ–Π΄ΠΈ Ρ– встановити Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½Ρ–ΡΡ‚ΡŒ Ρ—Ρ… Π²Π·Π°Ρ”ΠΌΠΎΠ΄Ρ–Ρ— Ρƒ Ρ‚Ρ€ΠΈΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½Ρ‚Π½Ρ–ΠΉ кондСнсації Π· 3-ΠΌΠ΅Ρ‚ΠΈΠ»-5-Π°ΠΌΡ–Π½ΠΎΠΏΡ–Ρ€Π°Π·ΠΎΠ»ΠΎΠΌ Ρ‚Π° 2,2-Π΄ΠΈΠΌΠ΅Ρ‚ΠΈΠ»-1,3-діоксан-4,6-Π΄Ρ–ΠΎΠ½ΠΎΠΌ.Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚ΠΈ Ρ‚Π° Ρ—Ρ… обговорСння. Π‘ΠΈΠ½Ρ‚Π΅Π·ΠΎΠ²Π°Π½ΠΎ ряд 1-Ρ„Π΅Π½Ρ–Π»-3-(4-алкоксифСніл)ΠΏΡ–Ρ€Π°Π·ΠΎΠ»-4-ΠΊΠ°Ρ€Π±Π°Π»ΡŒΠ΄Π΅Π³Ρ–Π΄Ρ–Π² Ρ„ΠΎΡ€ΠΌΡ–Π»ΡŽΠ²Π°Π½Π½ΡΠΌ Π°Ρ€ΠΈΠ»Π³Ρ–Π΄Ρ€Π°Π·ΠΎΠ½Ρ–Π² Π·Π° Π’Ρ–Π»ΡŒΡΠΌΠ΅ΠΉΠ΅Ρ€ΠΎΠΌβ€“Π₯Π°Π°ΠΊΠΎΠΌ. Π”ΠΎΠΌΡ–Π½ΠΎ-Ρ€Π΅Π°ΠΊΡ†Ρ–Ρ— Ρ†ΠΈΡ… Π°Π»ΡŒΠ΄Π΅Π³Ρ–Π΄Ρ–Π² Π· 3-ΠΌΠ΅Ρ‚ΠΈΠ»-5-Π°ΠΌΡ–Π½ΠΎΠΏΡ–Ρ€Π°Π·ΠΎΠ»ΠΎΠΌ Ρ‚Π° 2,2-Π΄ΠΈΠΌΠ΅Ρ‚ΠΈΠ»-1,3-діоксан-4,6-Π΄Ρ–ΠΎΠ½ΠΎΠΌ Π·Π°Π²Π΅Ρ€ΡˆΡƒΡŽΡ‚ΡŒΡΡ утворСнням ΠΏΡ–Ρ€Π°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΡ–Ρ€ΠΈΠ΄ΠΎΠ½ΠΎΠ²ΠΈΡ… систСм.Π•ΠΊΡΠΏΠ΅Ρ€ΠΈΠΌΠ΅Π½Ρ‚Π°Π»ΡŒΠ½Π° частина. Π‘ΠΈΠ½Ρ‚Π΅Π· 1-Ρ„Π΅Π½Ρ–Π»-3-(4-алкоксифСніл)ΠΏΡ–Ρ€Π°Π·ΠΎΠ»-4-ΠΊΠ°Ρ€Π±Π°Π»ΡŒΠ΄Π΅Π³Ρ–Π΄Ρ–Π² здійснСно Ρ„ΠΎΡ€ΠΌΡ–Π»ΡŽΠ²Π°Π½Π½ΡΠΌ Π°Ρ€ΠΈΠ»Π³Ρ–Π΄Ρ€Π°Π·ΠΎΠ½Ρ–Π² Π² ΡƒΠΌΠΎΠ²Π°Ρ… Ρ€Π΅Π°ΠΊΡ†Ρ–Ρ— Π’Ρ–Π»ΡŒΡΠΌΠ΅ΠΉΠ΅Ρ€Π°β€“Π₯Π°Π°ΠΊΠ° Π· Π²ΠΈΡ…ΠΎΠ΄ΠΎΠΌ 55 – 88 %. ΠšΠΈΠΏβ€™ΡΡ‚Ρ–Π½Π½ΡΠΌ Ρƒ 2-ΠΏΡ€ΠΎΠΏΠ°Π½ΠΎΠ»Ρ– ΡΡƒΠΌΡ–ΡˆΡ– Π΅ΠΊΠ²Ρ–ΠΌΠΎΠ»ΡŒΠ½ΠΈΡ… ΠΊΡ–Π»ΡŒΠΊΠΎΡΡ‚Π΅ΠΉ Ρ†ΠΈΡ… Π°Π»ΡŒΠ΄Π΅Π³Ρ–Π΄Ρ–Π², 3-ΠΌΠ΅Ρ‚ΠΈΠ»-5-Π°ΠΌΡ–Π½ΠΎΠΏΡ–Ρ€Π°Π·ΠΎΠ»Ρƒ Ρ‚Π° 2,2-Π΄ΠΈΠΌΠ΅Ρ‚ΠΈΠ»-1,3-діоксан-4,6-Π΄Ρ–ΠΎΠ½Ρƒ ΠΎΠ΄Π΅Ρ€ΠΆΠ°Π½ΠΎ 3-ΠΌΠ΅Ρ‚ΠΈΠ»-4-(1',3'-Π΄Ρ–Π°Ρ€ΠΈΠ»ΠΏΡ–Ρ€Π°Π·ΠΎΠ»-4'-Ρ–Π»)Ρ‚Π΅Ρ‚Ρ€Π°Π³Ρ–Π΄Ρ€ΠΎΠΏΡ–Ρ€Π°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΡ–Ρ€ΠΈΠ΄ΠΈΠ½-6-ΠΎΠ½ΠΈ. Π’ΠΈΡ…Ρ–Π΄ Ρ†Ρ–Π»ΡŒΠΎΠ²ΠΈΡ… сполук – 48 – 75 %. Π‘Ρ‚Ρ€ΡƒΠΊΡ‚ΡƒΡ€Ρƒ Ρ– склад усіх синтСзованих Ρ€Π΅Ρ‡ΠΎΠ²ΠΈΠ½ Π΄ΠΎΠ²Π΅Π΄Π΅Π½ΠΎ Π΄Π°Π½ΠΈΠΌΠΈ 1Н ЯМР-, Π†Π§-спСктрів Ρ‚Π° Π΅Π»Π΅ΠΌΠ΅Π½Ρ‚Π½ΠΈΠΌ Π°Π½Π°Π»Ρ–Π·ΠΎΠΌ.Висновки. ВстановлСно, Ρ‰ΠΎ Ρ€Π΅Π°ΠΊΡ†Ρ–Ρ— 1,3-Π΄Ρ–Π°Ρ€ΠΈΠ»Π·Π°ΠΌΡ–Ρ‰Π΅Π½ΠΈΡ… ΠΏΡ–Ρ€Π°Π·ΠΎΠ»-4-ΠΊΠ°Ρ€Π±Π°Π»ΡŒΠ΄Π΅Π³Ρ–Π΄Ρ–Π² Π· 3-ΠΌΠ΅Ρ‚ΠΈΠ»-5-Π°ΠΌΡ–Π½ΠΎΠΏΡ–Ρ€Π°Π·ΠΎΠ»ΠΎΠΌ Ρ‚Π° 2,2‑димСтил-1,3-діоксан-4,6-Π΄Ρ–ΠΎΠ½ΠΎΠΌ Ρ” рСгіосСлСктивними Ρ– Π·Π°Π²Π΅Ρ€ΡˆΡƒΡŽΡ‚ΡŒΡΡ утворСнням Π²ΠΈΠΊΠ»ΡŽΡ‡Π½ΠΎ 3,4-ΠΏΡ–Ρ€Π°Π·ΠΎΠ»ΠΎ[3,4-b]-ΠΏΡ–Ρ€ΠΈΠ΄ΠΈΠ½-6-ΠΎΠ½ΠΎΠ²ΠΈΡ… систСм. Π’Π°ΠΊΠ° Π½Π°ΠΏΡ€Π°Π²Π»Π΅Π½Ρ–ΡΡ‚ΡŒ процСсу Π²Ρ–Π΄ΠΏΠΎΠ²Ρ–Π΄Π°Ρ” Π²Π·Π°Ρ”ΠΌΠΎΠ΄Ρ–Ρ— Ξ²-Π²ΡƒΠ³Π»Π΅Ρ†Π΅Π²ΠΎΠ³ΠΎ Π°Ρ‚ΠΎΠΌΠ° ΠΉΠΌΠΎΠ²Ρ–Ρ€Π½ΠΎΠ³ΠΎ Ρ–Π½Ρ‚Π΅Ρ€ΠΌΠ΅Π΄Ρ–Π°Ρ‚Ρƒ, який ΡƒΡ‚Π²ΠΎΡ€ΡŽΡ”Ρ‚ΡŒΡΡ Π½Π° ΠΏΠ΅Ρ€ΡˆΡ–ΠΉ стадії Π· діоксандіону Ρ‚Π° Π°Π»ΡŒΠ΄Π΅Π³Ρ–Π΄Ρƒ, Π· Π²ΡƒΠ³Π»Π΅Ρ†Π΅Π²ΠΈΠΌ Π½ΡƒΠΊΠ»Π΅ΠΎΡ„Ρ–Π»ΡŒΠ½ΠΈΠΌ Ρ†Π΅Π½Ρ‚Ρ€ΠΎΠΌ Ρƒ ΠΌΠΎΠ»Π΅ΠΊΡƒΠ»Ρ– Π°ΠΌΡ–Π½ΠΎΠ°Π·ΠΎΠ»Ρƒ, Π° Π°Ρ‚ΠΎΠΌΠ° Π²ΡƒΠ³Π»Π΅Ρ†ΡŽ Π‘=О Π³Ρ€ΡƒΠΏΠΈ діоксан-4,6-Π΄Ρ–ΠΎΠ½Ρƒ – Π· Π΅ΠΊΠ·ΠΎΡ†ΠΈΠΊΠ»Ρ–Ρ‡Π½ΠΎΡŽ Π°ΠΌΡ–Π½ΠΎΠ³Ρ€ΡƒΠΏΠΎΡŽ Π³Π΅Ρ‚Π΅Ρ€ΠΈΠ»Π°ΠΌΡ–Π½Ρƒ.Β Received: 13.01.2019Revised: 31.01.2020Accepted: 27.02.202

    Transcriptional Regulation of VEGF-A by the Unfolded Protein Response Pathway

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    BACKGROUND: Angiogenesis is crucial to many physiological and pathological processes including development and cancer cell survival. Vascular endothelial growth factor-A (VEGFA) is the predominant mediator of angiogenesis in the VEGF family. During development, adverse environmental conditions like nutrient deprivation, hypoxia and increased protein secretion occur. IRE1alpha, PERK, and ATF6alpha, master regulators of the unfolded protein response (UPR), are activated under these conditions and are proposed to have a role in mediating angiogenesis. PRINCIPAL FINDINGS: Here we show that IRE1alpha, PERK, and ATF6alpha powerfully regulate VEGFA mRNA expression under various stress conditions. In Ire1alpha(-/-) and Perk(-/-) mouse embryonic fibroblasts and ATF6alpha-knockdown HepG2 cells, induction of VEGFA mRNA by endoplasmic reticulum stress is attenuated as compared to control cells. Embryonic lethality of Ire1alpha-/- mice is due to the lack of VEGFA induction in labyrinthine trophoblast cells of the developing placenta. Rescue of IRE1alpha and PERK in Ire1alpha(-/-) and Perk(-/-) cells respectively, prevents VEGFA mRNA attenuation. We further report that the induction of VEGFA by IRE1alpha, PERK and ATF6 involves activation of transcription factors, spliced-XBP-1, ATF4 and cleaved ATF6 respectively. CONCLUSIONS/SIGNIFICANCE: Our results reveal that the IRE1alpha-XBP-1, PERK-ATF4, and ATF6alpha pathways constitute novel upstream regulatory pathways of angiogenesis by modulating VEGF transcription. Activation of these pathways helps the rapidly growing cells to obtain sufficient nutrients and growth factors for their survival under the prevailing hostile environmental conditions. These results establish an important role of the UPR in angiogenesis

    Coriolis Effect in Optics: Unified Geometric Phase and Spin-Hall Effect

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    We examine the spin-orbit coupling effects that appear when a wave carrying intrinsic angular momentum interacts with a medium. The Berry phase is shown to be a manifestation of the Coriolis effect in a non-inertial reference frame attached to the wave. In the most general case, when both the direction of propagation and the state of the wave are varied, the phase is given by a simple expression that unifies the spin redirection Berry phase and the Pancharatnam--Berry phase. The theory is supported by the experiment demonstrating the spin-orbit coupling of electromagnetic waves via a surface plasmon nano-structure. The measurements verify the unified geometric phase, demonstrated by the observed polarization-dependent shift (spin-Hall effect) of the waves.Comment: 4 pages, 3 figure

    Some Experiments on the influence of Problem Hardness in Morphological Development based Learning of Neural Controllers

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    Natural beings undergo a morphological development process of their bodies while they are learning and adapting to the environments they face from infancy to adulthood. In fact, this is the period where the most important learning pro-cesses, those that will support learning as adults, will take place. However, in artificial systems, this interaction between morphological development and learning, and its possible advantages, have seldom been considered. In this line, this paper seeks to provide some insights into how morphological development can be harnessed in order to facilitate learning in em-bodied systems facing tasks or domains that are hard to learn. In particular, here we will concentrate on whether morphological development can really provide any advantage when learning complex tasks and whether its relevance towards learning in-creases as tasks become harder. To this end, we present the results of some initial experiments on the application of morpho-logical development to learning to walk in three cases, that of a quadruped, a hexapod and that of an octopod. These results seem to confirm that as task learning difficulty increases the application of morphological development to learning becomes more advantageous.Comment: 10 pages, 4 figure

    Morphological communication: exploiting coupled dynamics in a complex mechanical structure to achieve locomotion

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    Traditional engineering approaches strive to avoid, or actively suppress, nonlinear dynamic coupling among components. Biological systems, in contrast, are often rife with these dynamics. Could there be, in some cases, a benefit to high degrees of dynamical coupling? Here we present a distributed robotic control scheme inspired by the biological phenomenon of tensegrity-based mechanotransduction. This emergence of morphology-as-information-conduit or β€˜morphological communication’, enabled by time-sensitive spiking neural networks, presents a new paradigm for the decentralized control of large, coupled, modular systems. These results significantly bolster, both in magnitude and in form, the idea of morphological computation in robotic control. Furthermore, they lend further credence to ideas of embodied anatomical computation in biological systems, on scales ranging from cellular structures up to the tendinous networks of the human hand
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