973 research outputs found
Structure of 2-Methyl-5,6,7-triphenyl-6,7-dihydropyrazolo[2,3-\u3cem\u3ea\u3c/em\u3e]pyrimidine
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‘ΠΈΠ½ΡΠ΅Π· 7-Π°ΡΠΈΠ»-6,7-Π΄ΠΈΠ³ΡΠ΄ΡΠΎΡΠ΅ΡΡΠ°Π·ΠΎΠ»ΠΎ[1,5-a]ΠΏΡΡΠΈΠΌΡΠ΄ΠΈΠ½-5(4H)-ΠΎΠ½ΡΠ²
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.Π¦ΠΈΠΊΠ»ΠΎΠΊΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΠΈΠΈ 1Π-ΡΠ΅ΡΡΠ°Π·ΠΎΠ»-5-Π°ΠΌΠΈΠ½Π° Ρ ΠΌΠ΅ΡΠΈΠ»ΡΠΈΠ½Π½Π°ΠΌΠ°ΡΠ°ΠΌΠΈ, Π°ΡΠΈΠ»ΠΌΠ΅ΡΠΈΠ»ΠΈΠ΄Π΅Π½ΠΌΠ°Π»ΠΎΠ½ΠΎΠ²ΡΠΌΠΈ ΠΊΠΈΡΠ»ΠΎΡΠ°ΠΌΠΈ ΠΈ Π°ΡΠΈΠ»ΠΌΠ΅ΡΠΈΠ»ΠΈΠ΄Π΅Π½ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΡΠΌΠΈ 2,2-Π΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΠΈΠΎΠΊΡΠ°Π½-4,6-Π΄ΠΈΠΎΠ½Π° (ΠΊΠΈΡΠ»ΠΎΡΡ ΠΠ΅Π»ΡΠ΄ΡΡΠΌΠ°) ΠΏΡΠΎΠΈΡΡ
ΠΎΠ΄ΡΡ ΡΠ΅Π³ΠΈΠΎΡΠ΅Π»Π΅ΠΊΡΠΈΠ²Π½ΠΎ ΠΈ ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡ ΠΊ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΡ 7-Π°ΡΠΈΠ»-6,7-Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΡΠ΅ΡΡΠ°Π·ΠΎΠ»ΠΎ[1,5-a]ΠΏΠΈΡΠΈΠΌΠΈΠ΄ΠΈΠ½- 5(4Π)-ΠΎΠ½ΠΎΠ². ΠΠ°ΠΏΡΠ°Π²Π»Π΅Π½Π½ΠΎΡΡΡ ΡΠΎΡΠΌΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΠΈΡΠΈΠΌΠΈΠ΄ΠΈΠ½ΠΎΠ²ΠΎΠ³ΠΎ ΠΊΠΎΠ»ΡΡΠ° ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΡΠ΅Ρ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ Π°ΡΠΎΠΌΠ° ΡΠ³Π»Π΅ΡΠΎΠ΄Π°, Π½Π°Ρ
ΠΎΠ΄ΡΡΠ΅Π³ΠΎΡΡ Π² Ξ²-ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΠΈ Π½Π΅Π½Π°ΡΡΡΠ΅Π½Π½ΠΎΠ³ΠΎ ΠΊΠ°ΡΠ±ΠΎΠ½ΠΈΠ»ΡΠ½ΠΎΠ³ΠΎ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ, Ρ ΡΠ½Π΄ΠΎΡΠΈΠΊΠ»ΠΈΡΠ΅ΡΠΊΠΈΠΌ Π°ΡΠΎΠΌΠΎΠΌ Π°Π·ΠΎΡΠ°, Π° ΠΊΠ°ΡΠ±ΠΎΠ½ΠΈΠ»ΡΠ½ΠΎΠΉ Π³ΡΡΠΏΠΏΡ β Ρ Π°ΠΌΠΈΠ½ΠΎΠ³ΡΡΠΏΠΏΠΎΠΉ Π² ΠΌΠΎΠ»Π΅ΠΊΡΠ»Π΅ Π°ΠΌΠΈΠ½ΠΎΠ°Π·ΠΎΠ»Π°. Π‘ΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΈΠ·ΠΎΠΌΠ΅ΡΠ½ΠΎΠ³ΠΎ ΡΡΡΠΎΠ΅Π½ΠΈΡ Π½ΠΈ Π² ΠΎΠ΄Π½ΠΎΠΌ ΠΈΠ· ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠΎΠ² Π½Π΅ Π²ΡΡΠ²Π»Π΅Π½Ρ. Π‘ΠΎΡΡΠ°Π² ΠΈ ΡΡΡΠΎΠ΅Π½ΠΈΠ΅ Π²ΠΏΠ΅ΡΠ²ΡΠ΅ ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΡΠ΅ΡΡΠ°Π·ΠΎΠ»ΠΎ[1,5-a]ΠΏΠΈΡΠΈΠΌΠΈΠ΄ΠΈΠ½-5(4Π)-ΠΎΠ½ΠΎΠ² Π΄ΠΎΠΊΠ°Π·Π°Π½Ρ ΠΏΡΠΈ ΠΏΠΎΠΌΠΎΡΠΈ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π°, ΠΈΠ½ΡΡΠ°ΠΊΡΠ°ΡΠ½ΠΎΠΉ ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΠΈΠΈ (ΠΠ), ΡΠ΄Π΅ΡΠ½ΠΎΠ³ΠΎ ΠΌΠ°Π³Π½ΠΈΡΠ½ΠΎΠ³ΠΎ ΡΠ΅Π·ΠΎΠ½Π°Π½ΡΠ° Π½Π° ΠΏΡΠΎΡΠΎΠ½Π°Ρ
(Π―ΠΠ 1Π) ΠΈ ΠΌΠ°ΡΡΡΠΏΠ΅ΠΊΡΡΠΎΠΌΠ΅ΡΡΠΈΠΈ. ΠΠΈΡΡΡΠ°Π»ΡΠ½ΡΠΉ ΡΠΊΡΠΈΠ½ΠΈΠ½Π³ ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ
7-Π°ΡΠΈΠ»-6,7-Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΡΠ΅ΡΡΠ°Π·ΠΎΠ»ΠΎ[1,5-a]ΠΏΠΈΡΠΈΠΌΠΈΠ΄ΠΈΠ½-5(4Π)-ΠΎΠ½ΠΎΠ², ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π½ΡΠΉ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΌΡ PASS ΠΏΠΎ 780 Π²ΠΈΠ΄Π°ΠΌ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ, ΠΏΠΎΠΊΠ°Π·Π°Π», ΡΡΠΎ ΡΡΠΈ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΡΠ΅Π»Π΅ΡΠΎΠΎΠ±ΡΠ°Π·Π½ΠΎ ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°ΡΡ ΠΏΠΎ ΠΏΠΎΠΊΠ°Π·Π°ΡΠ΅Π»ΡΠΌ Π°Π½Π°Π»ΡΠ³Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΈ ΠΏΡΠΎΡΠΈΠ²ΠΎΠ²ΠΎΡΠΏΠ°Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ, Π° ΡΠ°ΠΊΠΆΠ΅ ΠΊΠ°ΠΊ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΡΠ΅ ΡΡΠ΅Π΄ΡΡΠ²Π° Π΄Π»Ρ Π»Π΅ΡΠ΅Π½ΠΈΡ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎΠΉ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎΡΡΠΈ.Π¦ΠΈΠΊΠ»ΠΎΠΊΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΡΡ 1Π-ΡΠ΅ΡΡΠ°Π·ΠΎΠ»-5-Π°ΠΌΡΠ½Ρ Π· ΠΌΠ΅ΡΠΈΠ»ΡΠΈΠ½Π°ΠΌΠ°ΡΠ°ΠΌΠΈ, Π°ΡΠΈΠ»ΠΌΠ΅ΡΠΈΠ»ΡΠ΄Π΅Π½ΠΌΠ°Π»ΠΎΠ½ΠΎΠ²ΠΈΠΌΠΈ ΠΊΠΈΡΠ»ΠΎΡΠ°ΠΌΠΈ ΡΠ° Π°ΡΠΈΠ»ΠΌΠ΅ΡΠΈΠ»ΡΠ΄Π΅Π½ΠΏΠΎΡ
ΡΠ΄Π½ΠΈΠΌΠΈ 2,2-Π΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΡΠΎΠΊΡΠ°Π½-4,6-Π΄ΡΠΎΠ½Ρ (ΠΊΠΈΡΠ»ΠΎΡΠΈ ΠΠ΅Π»ΡΠ΄ΡΡΠΌΠ°) Π²ΡΠ΄Π±ΡΠ²Π°ΡΡΡΡΡ ΡΠ΅Π³ΡΠΎΡΠ΅Π»Π΅ΠΊΡΠΈΠ²Π½ΠΎ ΡΠ° ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡΡ Π΄ΠΎ ΡΡΠ²ΠΎΡΠ΅Π½Π½Ρ 7-Π°ΡΠΈΠ»-6,7-Π΄ΠΈΠ³ΡΠ΄ΡΠΎΡΠ΅ΡΡΠ°Π·ΠΎΠ»ΠΎ[1,5-a]ΠΏΡΡΠΈΠΌΡΠ΄ΠΈΠ½-5(4Π)-ΠΎΠ½ΡΠ².ΠΠ°ΠΏΡΠ°Π²Π»Π΅Π½ΡΡΡΡ ΡΠΎΡΠΌΡΠ²Π°Π½Π½Ρ ΠΏΡΡΠΈΠΌΡΠ΄ΠΈΠ½ΠΎΠ²ΠΎΠ³ΠΎ ΠΊΡΠ»ΡΡΡ Π²ΡΠ΄ΠΏΠΎΠ²ΡΠ΄Π°Ρ Π²Π·Π°ΡΠΌΠΎΠ΄ΡΡ Π°ΡΠΎΠΌΠ° ΠΊΠ°ΡΠ±ΠΎΠ½Ρ Ρ Ξ²-ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½Π½Ρ Π½Π΅Π½Π°ΡΠΈΡΠ΅Π½ΠΎΡ ΠΊΠ°ΡΠ±ΠΎΠ½ΡΠ»ΡΠ½ΠΎΡ ΡΠΏΠΎΠ»ΡΠΊΠΈ Π· Π΅Π½Π΄ΠΎΡΠΈΠΊΠ»ΡΡΠ½ΠΈΠΌ Π°ΡΠΎΠΌΠΎΠΌ Π½ΡΡΡΠΎΠ³Π΅Π½Ρ, Π° ΠΊΠ°ΡΠ±ΠΎΠ½ΡΠ»ΡΠ½ΠΎΡ Π³ΡΡΠΏΠΈ β Π· Π°ΠΌΡΠ½ΠΎΠ³ΡΡΠΏΠΎΡ Π² ΠΌΠΎΠ»Π΅ΠΊΡΠ»Ρ Π°ΠΌΡΠ½ΠΎΠ°Π·ΠΎΠ»Ρ. Π‘ΠΏΠΎΠ»ΡΠΊ ΡΠ·ΠΎΠΌΠ΅ΡΠ½ΠΎΡ Π±ΡΠ΄ΠΎΠ²ΠΈ Π² ΠΆΠΎΠ΄Π½ΠΎΠΌΡ Π· Π΅ΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΡΠ² Π½Π΅ Π²ΠΈΡΠ²Π»Π΅Π½ΠΎ. Π‘ΠΊΠ»Π°Π΄ ΡΠ° Π±ΡΠ΄ΠΎΠ²Ρ Π²ΠΏΠ΅ΡΡΠ΅ ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΈΡ
ΡΠ΅ΡΡΠ°Π·ΠΎΠ»ΠΎ[1,5-a]ΠΏΡΡΠΈΠΌΡΠ΄ΠΈΠ½-5(4Π)-ΠΎΠ½ΡΠ² Π΄ΠΎΠ²Π΅Π΄Π΅Π½ΠΎ Π·Π° Π΄ΠΎΠΏΠΎΠΌΠΎΠ³ΠΎΡ Π΅Π»Π΅ΠΌΠ΅Π½ΡΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΡΠ·Ρ, ΡΠ½ΡΡΠ°ΡΠ΅ΡΠ²ΠΎΠ½ΠΎΡ ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΡΡ (ΠΠ§), ΡΠ΄Π΅ΡΠ½ΠΎΠ³ΠΎ ΠΌΠ°Π³Π½ΡΡΠ½ΠΎΠ³ΠΎ ΡΠ΅Π·ΠΎΠ½Π°Π½ΡΡ Π½Π° ΠΏΡΠΎΡΠΎΠ½Π°Ρ
(Π―ΠΠ 1Π) ΡΠ° ΠΌΠ°Ρ-ΡΠΏΠ΅ΠΊΡΡΠΎΠΌΠ΅ΡΡΡΡ. ΠΡΡΡΡΠ°Π»ΡΠ½ΠΈΠΉ ΡΠΊΡΠΈΠ½ΡΠ½Π³ 7-Π°ΡΠΈΠ»-6,7-Π΄ΠΈΠ³ΡΠ΄ΡΠΎΡΠ΅ΡΡΠ°Π·ΠΎΠ»ΠΎ[1,5-a]ΠΏΡΡΠΈΠΌΡΠ΄ΠΈΠ½-5(4Π)-ΠΎΠ½ΡΠ², ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠΉ ΡΠ· Π²ΠΈΠΊΠΎΡΠΈΡΡΠ°Π½Π½ΡΠΌ ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΈ PASS Π·Π° 780 Π²ΠΈΠ΄Π°ΠΌΠΈ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΡΡΠ½ΠΎΡ Π΄ΡΡ, Π·Π°ΡΠ²ΡΠ΄ΡΠΈΠ², ΡΠΎ ΡΡ ΡΠΏΠΎΠ»ΡΠΊΠΈ Π΄ΠΎΡΡΠ»ΡΠ½ΠΎ ΡΠ΅ΡΡΡΠ²Π°ΡΠΈ Π·Π° ΠΏΠΎΠΊΠ°Π·Π½ΠΈΠΊΠ°ΠΌΠΈ Π°Π½Π°Π»Π³Π΅ΡΠΈΡΠ½ΠΎΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ, Π° ΡΠ°ΠΊΠΎΠΆ ΡΠΊ ΠΏΠΎΡΠ΅Π½ΡΡΠΉΠ½Ρ Π·Π°ΡΠΎΠ±ΠΈ Π΄Π»Ρ Π»ΡΠΊΡΠ²Π°Π½Π½Ρ ΡΠ΅ΡΡΠ΅Π²ΠΎΡ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠ½ΠΎΡΡΡ
Observation of Macroscopic Structural Fluctuations in bcc Solid 4He
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₯ΡΠΌΡΡΠ½Ρ Π²Π»Π°ΡΡΠΈΠ²ΠΎΡΡΡ 3-(5-Π°ΠΌΡΠ½ΠΎ-1Π-1,2,4-ΡΡΠΈΠ°Π·ΠΎΠ»-1-ΡΠ»)- ΡΠ° 3-(2-Π°ΠΌΡΠ½ΠΎ-1Π-Π±Π΅Π½Π·ΠΎ[d]ΡΠΌΡΠ΄Π°Π·ΠΎΠ»-1-ΡΠ»)-3-ΡΠ΅Π½ΡΠ»ΠΏΡΠΎΠΏΠ°Π½Π³ΡΠ΄ΡΠ°Π·ΠΈΠ΄ΡΠ²
Reactions of 3-(5-amino-1H-1,2,4-triazol-1-yl)- and 3-(2-amΡno-1H-benzo[d]ΡmΡdazol-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-amΡno-1H-1,2,4-triazol-1-yl)-N1 benzilΡdene-3-phenylpropanehydrazide.Π Π΅Π°ΠΊΡΠΈΠΈ 3-(5-Π°ΠΌΠΈΠ½ΠΎ-1Π-1,2,4-ΡΡΠΈΠ°Π·ΠΎΠ»-1-ΠΈΠ»)- ΠΈ 3-(2-Π°ΠΌΠΈΠ½ΠΎ-1Π Π±Π΅Π½Π·ΠΎ[d]ΠΈΠΌΠΈΠ΄Π°Π·ΠΎΠ»-1-ΠΈΠ»)-3-ΡΠ΅Π½ΠΈΠ»ΠΏΡΠΎΠΏΠ°Π½Π³ΠΈΠ΄ΡΠ°Π·ΠΈΠ΄ΠΎΠ² Ρ ΠΊΠ°ΡΠ±ΠΎΠ½ΠΈΠ»ΡΠ½ΡΠΌΠΈ ΡΠ»Π΅ΠΊΡΡΠΎΡΠΈΠ»Π°ΠΌΠΈ β Π°ΡΠ΅ΡΠΈΠ»Π°ΡΠ΅ΡΠΎΠ½ΠΎΠΌ, Π°ΡΠΎΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΠΈ Π³Π΅ΡΠ΅ΡΠΎΡΠΈΠΊΠ»ΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ Π°Π»ΡΠ΄Π΅Π³ΠΈΠ΄Π°ΠΌΠΈ Π² ΡΠΏΠΈΡΡΠΎΠ²ΠΎΠΉ ΡΡΠ΅Π΄Π΅ Π·Π°Π²Π΅ΡΡΠ°ΡΡΡΡ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΡΡΡΠΈΡ
Π³ΠΈΠ΄ΡΠ°Π·ΠΎΠ½ΠΎΠ² Π² Π²ΠΈΠ΄Π΅ Π-Π³Π΅ΠΎΠΌΠ΅ΡΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΠ·ΠΎΠΌΠ΅ΡΠΎΠ² ΠΈ s-trans/cis ΠΊΠΎΠ½ΡΠΎΡΠΌΠ΅ΡΠΎΠ² ΠΏΠΎ ΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΡ ΠΊ Π°ΠΌΠΈΠ΄Π½ΠΎΠΉ ΡΠ²ΡΠ·ΠΈ. Π Π±ΠΎΠ»Π΅Π΅ ΠΆΠ΅ΡΡΠΊΠΈΡ
ΡΡΠ»ΠΎΠ²ΠΈΡΡ
ΠΏΡΠΎΠΈΡΡ
ΠΎΠ΄ΠΈΡ ΡΠ»ΠΈΠΌΠΈΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π³ΠΈΠ΄ΡΠ°Π·ΠΎΠ½Π½ΡΡ
ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΈ ΡΠ΅ΡΡΠΎΠΊΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΠΈΡ Π°ΠΌΠΈΠ½ΠΎΠ°Π·ΠΎΠ»ΠΎΡΠ΅Π½ΠΈΠ»ΠΏΡΠΎΠΏΠΈΠΎΠ½ΠΈΠ»ΡΠ½ΡΡ
ΠΎΡΡΠ°ΡΠΊΠΎΠ² Π² Π΄ΠΈΠ³ΠΈΠ΄ΡΠΎΠ°Π·ΠΎΠ»ΠΎΠΏΠΈΡΠΈΠΌΠΈΠ΄ΠΈΠ½ΠΎΠ½Ρ. Π‘ΠΎΡΡΠ°Π² ΠΈ ΡΡΡΠΎΠ΅Π½ΠΈΠ΅ Π²ΠΏΠ΅ΡΠ²ΡΠ΅ ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π³ΠΈΠ΄ΡΠ°Π·ΠΎΠ½ΠΎΠ² Π΄ΠΎΠΊΠ°Π·Π°Π½ΠΎ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π°, ΠΈΠ½ΡΡΠ°ΠΊΡΠ°ΡΠ½ΠΎΠΉ ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΠΈΠΈ (ΠΠ), ΡΠ΄Π΅ΡΠ½ΠΎΠ³ΠΎ ΠΌΠ°Π³Π½ΠΈΡΠ½ΠΎΠ³ΠΎ ΡΠ΅Π·ΠΎΠ½Π°Π½ΡΠ° Π½Π° ΠΏΡΠΎΡΠΎΠ½Π°Ρ
(Π―ΠΠ 1Π) ΠΈ ΠΌΠ°ΡΡ-ΡΠΏΠ΅ΠΊΡΡΠΎΠΌΠ΅ΡΡΠΈΠΈ. ΠΠΈΡΡΡΠ°Π»ΡΠ½ΡΠΉ ΡΠΊΡΠΈΠ½ΠΈΠ½Π³ ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ
Π²Π΅ΡΠ΅ΡΡΠ², ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π½ΡΠΉ Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΌΡ PASS ΠΏΠΎ 780 Π²ΠΈΠ΄Π°ΠΌ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ, ΠΏΠΎΠΊΠ°Π·Π°Π», ΡΡΠΎ ΡΡΠΈ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΡΠ΅Π»Π΅ΡΠΎΠΎΠ±ΡΠ°Π·Π½ΠΎ ΡΠ΅ΡΡΠΈΡΠΎΠ²Π°ΡΡ Π½Π° Π½Π°Π»ΠΈΡΠΈΠ΅ Ρ Π½ΠΈΡ
Π°Π½ΡΠΈΠ±Π°ΠΊΡΠ΅ΡΠΈΠ°Π»ΡΠ½ΡΡ
ΠΈ ΡΡΠ½Π³ΠΈΡΠΈΠ΄Π½ΡΡ
ΡΠ²ΠΎΠΉΡΡΠ². ΠΠ΄Π½Π°ΠΊΠΎ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½Π°Ρ ΠΎΡΠ΅Π½ΠΊΠ° Π°Π½ΡΠΈΠΌΠΈΠΊΡΠΎΠ±Π½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ N1-ΠΈΠ»ΠΈΠ΄Π΅Π½ΠΎΠ²ΡΡ
ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΡΡ
3-ΡΠ΅Π½ΠΈΠ»ΠΏΡΠΎΠΏΠ°Π½Π³ΠΈΠ΄ΡΠ°Π·ΠΈΠ΄ΠΎΠ², ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π½Π°Ρ Π½Π° ΠΏΡΡΠΈ ΠΌΡΠ·Π΅ΠΉΠ½ΡΡ
ΡΡΠ°ΠΌΠΌΠ°Ρ
ΡΠ΅ΡΡ-ΠΊΡΠ»ΡΡΡΡ, ΠΎΠ±Π½Π°ΡΡΠΆΠΈΠ»Π° ΡΠ»Π°Π±ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΎΡΠ½ΠΎΡΠΈΡΠ΅Π»ΡΠ½ΠΎ Staphylococcus aureus ΡΠΎΠ»ΡΠΊΠΎ Ρ 3-(5-Π°ΠΌΠΈΠ½ΠΎ-1Π-1,2,4-ΡΡΠΈΠ°Π·ΠΎΠ»-1-ΠΈΠ»)-N1-Π±Π΅Π½Π·ΠΈΠ»ΠΈΠ΄Π΅Π½-3 ΡΠ΅Π½ΠΈΠ»ΠΏΡΠΎΠΏΠ°Π½Π³ΠΈΠ΄ΡΠ°Π·ΠΈΠ΄Π°.Π Π΅Π°ΠΊΡΡΡ 3-(5-Π°ΠΌΡΠ½ΠΎ-1Π-1,2,4-ΡΡΠΈΠ°Π·ΠΎΠ»-1-ΡΠ»)- ΡΠ° 3-(2-Π°ΠΌΡΠ½ΠΎ-1Π-Π±Π΅Π½Π·ΠΎ[d]ΡΠΌΡΠ΄Π°Π·ΠΎΠ»-1-ΡΠ»)-3-ΡΠ΅Π½ΡΠ»ΠΏΡΠΎΠΏΠ°Π½Π³ΡΠ΄ΡΠ°Π·ΠΈΠ΄ΡΠ² Π· ΠΊΠ°ΡΠ±ΠΎΠ½ΡΠ»ΡΠ½ΠΈΠΌΠΈ Π΅Π»Π΅ΠΊΡΡΠΎΡΡΠ»Π°ΠΌΠΈ β Π°ΡΠ΅ΡΠΈΠ»Π°ΡΠ΅ΡΠΎΠ½ΠΎΠΌ, Π°ΡΠΎΠΌΠ°ΡΠΈΡΠ½ΠΈΠΌΠΈ ΡΠ° Π³Π΅ΡΠ΅ΡΠΎΡΠΈΠΊΠ»ΡΡΠ½ΠΈΠΌΠΈ Π°Π»ΡΠ΄Π΅Π³ΡΠ΄Π°ΠΌΠΈ Ρ ΡΠΏΠΈΡΡΠΎΠ²ΠΎΠΌΡ ΡΠ΅ΡΠ΅Π΄ΠΎΠ²ΠΈΡΡ Π·Π°Π²Π΅ΡΡΡΡΡΡΡΡ ΡΡΠ²ΠΎΡΠ΅Π½Π½ΡΠΌ Π²ΡΠ΄ΠΏΠΎΠ²ΡΠ΄Π½ΠΈΡ
Π³ΡΠ΄ΡΠ°Π·ΠΎΠ½ΡΠ² Ρ Π²ΠΈΠ³Π»ΡΠ΄Ρ Π-Π³Π΅ΠΎΠΌΠ΅ΡΡΠΈΡΠ½ΠΈΡ
ΡΠ·ΠΎΠΌΠ΅ΡΡΠ² Ρ s-trans/cis ΠΊΠΎΠ½ΡΠΎΡΠΌΠ΅ΡΡΠ² ΠΏΠΎ Π²ΡΠ΄Π½ΠΎΡΠ΅Π½Π½Ρ Π΄ΠΎ Π°ΠΌΡΠ΄Π½ΠΎΠ³ΠΎ Π·Π²βΡΠ·ΠΊΡ. Π Π±ΡΠ»ΡΡ ΠΆΠΎΡΡΡΠΊΠΈΡ
ΡΠΌΠΎΠ²Π°Ρ
Π²ΡΠ΄Π±ΡΠ²Π°ΡΡΡΡΡ Π΅Π»ΡΠΌΡΠ½ΡΠ²Π°Π½Π½Ρ Π³ΡΠ΄ΡΠ°Π·ΠΎΠ½Π½ΠΈΡ
ΡΡΠ°Π³ΠΌΠ΅Π½ΡΡΠ² ΡΠ° ΡΠ΅ΡΡΠΎΠΊΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΡΡ Π°ΠΌΡΠ½ΠΎΠ°Π·ΠΎΠ»ΠΎΡΠ΅Π½ΡΠ»ΠΏΡΠΎΠΏΡΠΎΠ½ΡΠ»ΡΠ½ΠΈΡ
Π·Π°Π»ΠΈΡΠΊΡΠ² Ρ Π΄ΠΈΠ³ΡΠ΄ΡΠΎΠ°Π·ΠΎΠ»ΠΎΠΏΡΡΠΈΠΌΡΠ΄ΠΈΠ½ΠΎΠ½ΠΈ. Π‘ΠΊΠ»Π°Π΄ ΡΠ° Π±ΡΠ΄ΠΎΠ²Ρ Π²ΠΏΠ΅ΡΡΠ΅ ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΈΡ
Π³ΡΠ΄ΡΠ°Π·ΠΎΠ½ΡΠ² Π΄ΠΎΠ²Π΅Π΄Π΅Π½ΠΎ Π·Π° Π΄ΠΎΠΏΠΎΠΌΠΎΠ³ΠΎΡ Π΅Π»Π΅ΠΌΠ΅Π½ΡΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΡΠ·Ρ, ΡΠ½ΡΡΠ°ΡΠ΅ΡΠ²ΠΎΠ½ΠΎΡ ΡΠΏΠ΅ΠΊΡΡΠΎΡΠΊΠΎΠΏΡΡ (ΠΠ§), ΡΠ΄Π΅ΡΠ½ΠΎΠ³ΠΎ ΠΌΠ°Π³Π½ΡΡΠ½ΠΎΠ³ΠΎ ΡΠ΅Π·ΠΎΠ½Π°Π½ΡΡ Π½Π° ΠΏΡΠΎΡΠΎΠ½Π°Ρ
(Π―ΠΠ 1Π) ΡΠ° ΠΌΠ°Ρ-ΡΠΏΠ΅ΠΊΡΡΠΎΠΌΠ΅ΡΡΡΡ. ΠΡΡΡΡΠ°Π»ΡΠ½ΠΈΠΉ ΡΠΊΡΠΈΠ½ΡΠ½Π³ ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΡ
ΡΠ΅ΡΠΎΠ²ΠΈΠ½, ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠΉ ΡΠ· Π²ΠΈΠΊΠΎΡΠΈΡΡΠ°Π½Π½ΡΠΌ ΠΏΡΠΎΠ³ΡΠ°ΠΌΠΈ PASS Π·Π° 780 Π²ΠΈΠ΄Π°ΠΌΠΈ ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΡΡΠ½ΠΎΡ Π΄ΡΡ, Π·Π°ΡΠ²ΡΠ΄ΡΠΈΠ², ΡΠΎ ΡΡ ΡΠΏΠΎΠ»ΡΠΊΠΈ Π΄ΠΎΡΡΠ»ΡΠ½ΠΎ ΡΠ΅ΡΡΡΠ²Π°ΡΠΈ Π½Π° Π½Π°ΡΠ²Π½ΡΡΡΡ Ρ Π½ΠΈΡ
Π°Π½ΡΠΈΠ±Π°ΠΊΡΠ΅ΡΡΠ°Π»ΡΠ½ΠΈΡ
ΡΠ° ΡΡΠ½Π³ΡΡΠΈΠ΄Π½ΠΈΡ
Π²Π»Π°ΡΡΠΈΠ²ΠΎΡΡΠ΅ΠΉ. ΠΠ΄Π½Π°ΠΊ Π΅ΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½Π° ΠΎΡΡΠ½ΠΊΠ° Π°Π½ΡΠΈΠΌΡΠΊΡΠΎΠ±Π½ΠΎΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ N1-ΡΠ»ΡΠ΄Π΅Π½ΠΎΠ²ΠΈΡ
ΠΏΠΎΡ
ΡΠ΄Π½ΠΈΡ
3-ΡΠ΅Π½ΡΠ»ΠΏΡΠΎΠΏΠ°Π½Π³ΡΠ΄ΡΠ°Π·ΠΈΠ΄ΡΠ², ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Π° Π½Π° ΠΏβΡΡΠΈ ΠΌΡΠ·Π΅ΠΉΠ½ΠΈΡ
ΡΡΠ°ΠΌΠ°Ρ
ΡΠ΅ΡΡ-ΠΊΡΠ»ΡΡΡΡ, Π²ΠΈΡΠ²ΠΈΠ»Π° ΡΠ»Π°Π±ΠΊΡ Π°ΠΊΡΠΈΠ²Π½ΡΡΡΡ Π²ΡΠ΄Π½ΠΎΡΠ½ΠΎ Staphylococcus aureus Π»ΠΈΡΠ΅ Ρ 3-(5-Π°ΠΌΡΠ½ΠΎ-1Π-1,2,4-ΡΡΠΈΠ°Π·ΠΎΠ»-1-ΡΠ»)-N1-Π±Π΅Π½Π·ΠΈΠ»ΡΠ΄Π΅Π½-3-ΡΠ΅Π½ΡΠ»ΠΏΡΠΎΠΏΠ°Π½Π³ΡΠ΄ΡΠ°Π·ΠΈΠ΄Ρ
ΠΠΎΠΌΡΠ½ΠΎ-ΡΠ΅Π°ΠΊΡΡΡ ΡΠ·Π°ΡΠΈΠ½ΡΠ² Π· 5-Π°ΠΌΡΠ½ΠΎΠΏΡΡΠ°Π·ΠΎΠ»Π°ΠΌΠΈ ΡΠ° 2,2-Π΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΡΠΎΠΊΡΠ°Π½-4,6-Π΄ΡΠΎΠ½ΠΎΠΌ
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 (Meldrumβs 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 Meldrumβs 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 Meldrumβs 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 Meldrumβs 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 β a domino process that starts formation of the predominant reaction products β pyrazolo[3,4-b]pyridine-4-spiroindolinones.Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ β ΡΡΡΠ°Π½ΠΎΠ²ΠΈΡΡ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½Π½ΠΎΡΡΡ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΈΠ·Π°ΡΠΈΠ½ΠΎΠ² Ρ 5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡΠ°Π·ΠΎΠ»Π°ΠΌΠΈ ΠΈ 2,2-Π΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΠΈΠΎΠΊΡΠ°Π½-4,6-Π΄ΠΈΠΎΠ½ΠΎΠΌ Π² ΡΠ°Π·Π½ΡΡ
ΡΡΠ»ΠΎΠ²ΠΈΡΡ
.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΈ ΠΈΡ
ΠΎΠ±ΡΡΠΆΠ΄Π΅Π½ΠΈΠ΅. ΠΠΎΠΌΠΈΠ½ΠΎ-ΡΠ΅Π°ΠΊΡΠΈΠΈ ΠΈΠ·Π°ΡΠΈΠ½ΠΎΠ², 5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡΠ°Π·ΠΎΠ»ΠΎΠ² ΠΈ 2,2-Π΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΠΈΠΎΠΊΡΠ°Π½-4,6-Π΄ΠΈΠΎΠ½Π° (ΠΊΠΈΡΠ»ΠΎΡΡ ΠΠ΅Π»ΡΠ΄ΡΡΠΌΠ°) Π² ΡΠΏΠΈΡΡΠΎΠ²ΠΎΠΉ ΡΡΠ΅Π΄Π΅ Π·Π°Π²Π΅ΡΡΠ°ΡΡΡΡ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΡΠΌΠ΅ΡΠ΅ΠΉ ΠΏΠΈΡΠ°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΠΈΡΠΈΠ΄ΠΈΠ½-4-ΡΠΏΠΈΡΠΎΠΈΠ½Π΄ΠΎΠ»ΠΈΠ½ΠΎΠ½ΠΎΠ² ΠΈ 3-(5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡΠ°Π·ΠΎΠ»-3-ΠΈΠ»)-3-Π³ΠΈΠ΄ΡΠΎΠΊΡΠΈ-2-ΠΎΠΊΡΠΈΠ½Π΄ΠΎΠ»ΠΈΠ½ΠΎΠ² Ρ ΠΏΡΠ΅ΠΎΠ±Π»Π°Π΄Π°ΡΡΠΈΠΌ ΡΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅ΠΌ ΡΠΏΠΈΡΠΎ-ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ. 3-(5-ΠΠΌΠΈΠ½ΠΎΠΏΠΈΡΠ°Π·ΠΎΠ»-4-ΠΈΠ»)-3-Π³ΠΈΠ΄ΡΠΎΠΊΡΠΈ-2-ΠΎΠΊΡΠΈΠ½Π΄ΠΎΠ»ΠΈΠ½Ρ Π»ΠΈΡΡ Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΡΠ΅ΡΡΠΎΡΠ°ΡΠΏΠ°Π΄Π° Π½Π° ΠΈΡΡ
ΠΎΠ΄Π½ΡΠ΅ ΠΈΠ·Π°ΡΠΈΠ½ ΠΈ Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡΠ°Π·ΠΎΠ» Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ ΠΊΠΈΡΠ»ΠΎΡΡ ΠΠ΅Π»ΡΠ΄ΡΡΠΌΠ° ΠΌΠΎΠ³ΡΡ ΠΎΡΠ΅Π½Ρ ΠΌΠ΅Π΄Π»Π΅Π½Π½ΠΎ Ρ Π½ΠΈΠ·ΠΊΠΈΠΌΠΈ Π²ΡΡ
ΠΎΠ΄Π°ΠΌΠΈ ΠΏΡΠ΅Π²ΡΠ°ΡΠ°ΡΡΡΡ Π² ΠΏΠΈΡΠ°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΠΈΡΠΈΠ΄ΠΈΠ½-4-ΡΠΏΠΈΡΠΎΠΈΠ½Π΄ΠΎΠ»ΠΈΠ½ΠΎΠ½Ρ.ΠΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½Π°Ρ ΡΠ°ΡΡΡ. ΠΠΈΠΏΡΡΠ΅Π½ΠΈΠ΅ΠΌ Π² ΠΌΠ΅ΡΠ°Π½ΠΎΠ»Π΅ ΡΠΊΠ²ΠΈΠΌΠΎΠ»ΡΠ½ΡΡ
ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ² ΠΈΠ·Π°ΡΠΈΠ½ΠΎΠ², 5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡΠ°Π·ΠΎΠ»ΠΎΠ² ΠΈ ΠΊΠΈΡΠ»ΠΎΡΡ ΠΠ΅Π»ΡΠ΄ΡΡΠΌΠ° ΠΏΠΎΠ»ΡΡΠ΅Π½Ρ ΡΠΌΠ΅ΡΠΈ ΠΏΠΈΡΠ°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΠΈΡΠΈΠ΄ΠΈΠ½-4-ΡΠΏΠΈΡΠΎΠΈΠ½Π΄ΠΎΠ»ΠΈΠ½ΠΎΠ½ΠΎΠ² ΠΈ 3-(5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡΠ°Π·ΠΎΠ»-3-ΠΈΠ»)-3-Π³ΠΈΠ΄ΡΠΎΠΊΡΠΈ-2-ΠΎΠΊΡΠΈΠ½Π΄ΠΎΠ»ΠΈΠ½ΠΎΠ², ΠΊΠΎΡΠΎΡΡΠ΅ ΡΠ°Π·Π΄Π΅Π»Π΅Π½Ρ ΠΊΡΠΈΡΡΠ°Π»Π»ΠΈΠ·Π°ΡΠΈΠ΅ΠΉ. ΠΡΡ
ΠΎΠ΄ ΡΠΏΠΈΡΠΎ-ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ ΡΠΎΡΡΠ°Π²Π»ΡΠ΅Ρ 26-82 %, Π° 3-(5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡΠ°Π·ΠΎΠ»-3-ΠΈΠ»)-3-Π³ΠΈΠ΄ΡΠΎΠΊΡΠΈ-2-ΠΎΠΊΡΠΈΠ½Π΄ΠΎΠ»ΠΈΠ½ΠΎΠ² β 5-23 %. ΠΡΠ΅Π²ΡΠ°ΡΠ΅Π½ΠΈΠ΅ ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΡ
Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ ΠΊΠΈΡΠ»ΠΎΡΡ ΠΠ΅Π»ΡΠ΄ΡΡΠΌΠ° Π² ΡΠΏΠΈΡΠΎ-ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΏΡΠΎΠΈΡΡ
ΠΎΠ΄ΠΈΡ ΠΏΡΠΈ Π΄Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠΌ ΠΊΠΈΠΏΡΡΠ΅Π½ΠΈΠΈ Π² ΡΠΏΠΈΡΡΠΎΠ²ΠΎΠΉ ΡΡΠ΅Π΄Π΅ ΠΈ ΡΠΎΠΏΡΠΎΠ²ΠΎΠΆΠ΄Π°Π΅ΡΡΡ ΠΊΡΠ°ΠΉΠ½Π΅ Π½ΠΈΠ·ΠΊΠΈΠΌΠΈ Π²ΡΡ
ΠΎΠ΄Π°ΠΌΠΈ. Π‘ΡΡΠΎΠ΅Π½ΠΈΠ΅ ΠΈ ΡΠΎΡΡΠ°Π² Π²ΡΠ΅Ρ
ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ Π΄ΠΎΠΊΠ°Π·Π°Π½Ρ Π΄Π°Π½Π½ΡΠΌΠΈ Π―ΠΠ 1Π, ΠΌΠ°ΡΡ-ΡΠΏΠ΅ΠΊΡΡΠΎΠ² ΠΈ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠ½ΡΠΌ Π°Π½Π°Π»ΠΈΠ·ΠΎΠΌ.ΠΡΠ²ΠΎΠ΄Ρ. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ Π² ΡΡΠ΅Ρ
ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠ½ΡΡ
ΡΠ΅Π°ΠΊΡΠΈΡΡ
ΠΈΠ·Π°ΡΠΈΠ½ΠΎΠ², 5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡΠ°Π·ΠΎΠ»ΠΎΠ² ΠΈ 2,2-Π΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΠΈΠΎΠΊΡΠ°Π½-4,6-Π΄ΠΈΠΎΠ½Π° ΡΠ΅Π°Π»ΠΈΠ·ΡΡΡΡΡ Π΄Π²Π° ΠΊΠΎΠ½ΠΊΡΡΠΈΡΡΡΡΠΈΡ
Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΠΈΡ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΈΠ·Π°ΡΠΈΠ½Π° Ρ Π½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ»Π°ΠΌΠΈ. ΠΠ΄Π½ΠΎ ΠΈΠ· Π½ΠΈΡ
β Π½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ»ΡΠ½ΠΎΠ΅ ΠΏΡΠΈΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅ Π‘4 ΡΠ΅Π°ΠΊΡΠΈΠΎΠ½Π½ΠΎΠ³ΠΎ ΡΠ΅Π½ΡΡΠ° Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡΠ°Π·ΠΎΠ»Π° ΠΊ ΠΊΠ°ΡΠ±ΠΎΠ½ΠΈΠ»ΡΠ½ΠΎΠΉ Π³ΡΡΠΏΠΏΠ΅ ΠΈΠ·Π°ΡΠΈΠ½Π° ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ 3-(5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡΠ°Π·ΠΎΠ»-4-ΠΈΠ»)-3-Π³ΠΈΠ΄ΡΠΎΠΊΡΠΈ-2-ΠΎΠΊΡΠΈΠ½Π΄ΠΎΠ»ΠΈΠ½Π°ΠΌ. Π Π²ΡΠΎΡΠΎΠ΅ β ΠΊΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΠΈΡ ΠΈΠ·Π°ΡΠΈΠ½Π° Ρ Π΄ΠΈΠΎΠΊΡΠ°Π½-4,6-Π΄ΠΈΠΎΠ½ΠΎΠΌ ΠΏΠΎ ΠΠ½Π΅Π²Π΅Π½Π°Π³Π΅Π»Ρ ΠΈΠ½ΠΈΡΠΈΠΈΡΡΠ΅Ρ Π΄ΠΎΠΌΠΈΠ½ΠΎ-ΠΏΡΠΎΡΠ΅ΡΡ, ΠΊΠΎΡΠΎΡΡΠΉ Π·Π°Π²Π΅ΡΡΠ°Π΅ΡΡΡ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΎΡΠ½ΠΎΠ²Π½ΡΡ
ΠΏΡΠΎΠ΄ΡΠΊΡΠΎΠ² ΡΠ΅Π°ΠΊΡΠΈΠΈ β ΠΏΠΈΡΠ°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΠΈΡΠΈΠ΄ΠΈΠ½-4-ΡΠΏΠΈΡΠΎΠΈΠ½Π΄ΠΎΠ»ΠΈΠ½ΠΎΠ½ΠΎΠ².ΠΠ΅ΡΠ° ΡΠΎΠ±ΠΎΡΠΈ β Π²ΡΡΠ°Π½ΠΎΠ²ΠΈΡΠΈ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΡΡΡΡ Π²Π·Π°ΡΠΌΠΎΠ΄ΡΡ ΡΠ·Π°ΡΠΈΠ½ΡΠ² Π· 5-Π°ΠΌΡΠ½ΠΎΠΏΡΡΠ°Π·ΠΎΠ»Π°ΠΌΠΈ ΡΠ° 2,2-Π΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΡΠΎΠΊΡΠ°Π½-4,6-Π΄ΡΠΎΠ½ΠΎΠΌ Ρ ΡΡΠ·Π½ΠΈΡ
ΡΠΌΠΎΠ²Π°Ρ
.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΠΈ ΡΠ° ΡΡ
ΠΎΠ±Π³ΠΎΠ²ΠΎΡΠ΅Π½Π½Ρ. ΠΠΎΠΌΡΠ½ΠΎ-ΡΠ΅Π°ΠΊΡΡΡ ΡΠ·Π°ΡΠΈΠ½ΡΠ², 5-Π°ΠΌΡΠ½ΠΎΠΏΡΡΠ°Π·ΠΎΠ»ΡΠ² ΡΠ° 2,2-Π΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΡΠΎΠΊΡΠ°Π½-4,6-Π΄ΡΠΎΠ½Ρ (ΠΊΠΈΡΠ»ΠΎΡΠΈ ΠΠ΅Π»ΡΠ΄ΡΡΠΌΠ°) Ρ ΡΠΏΠΈΡΡΠΎΠ²ΠΎΠΌΡ ΡΠ΅ΡΠ΅Π΄ΠΎΠ²ΠΈΡΡ Π·Π°Π²Π΅ΡΡΡΡΡΡΡΡ ΡΡΠ²ΠΎΡΠ΅Π½Π½ΡΠΌ ΡΡΠΌΡΡΡ ΠΏΡΡΠ°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΡΡΠΈΠ΄ΠΈΠ½-4-ΡΠΏΡΡΠΎΡΠ½Π΄ΠΎΠ»ΡΠ½ΠΎΠ½ΡΠ² ΡΠ° 3-(5-Π°ΠΌΡΠ½ΠΎΠΏΡΡΠ°Π·ΠΎΠ»-3-ΡΠ»)-3-Π³ΡΠ΄ΡΠΎΠΊΡΠΈ-2-ΠΎΠΊΡΡΠ½Π΄ΠΎΠ»ΡΠ½ΡΠ² Π· ΠΏΠ΅ΡΠ΅Π²Π°ΠΆΠ½ΠΈΠΌ Π²ΠΌΡΡΡΠΎΠΌ ΡΠΏΡΡΠΎ-ΡΠΏΠΎΠ»ΡΠΊ. 3-(5-ΠΠΌΡΠ½ΠΎΠΏΡΡΠ°Π·ΠΎΠ»-4-ΡΠ»)-3-Π³ΡΠ΄ΡΠΎΠΊΡΠΈ-2-ΠΎΠΊΡΡΠ½Π΄ΠΎΠ»ΡΠ½ΠΈ Π»ΠΈΡΠ΅ Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ ΡΠ΅ΡΡΠΎΡΠΎΠ·ΠΏΠ°Π΄Ρ Π½Π° Π²ΠΈΡ
ΡΠ΄Π½Ρ ΡΠ·Π°ΡΠΈΠ½ ΡΠ° Π°ΠΌΡΠ½ΠΎΠΏΡΡΠ°Π·ΠΎΠ» Ρ ΠΏΡΠΈΡΡΡΠ½ΠΎΡΡΡ ΠΊΠΈΡΠ»ΠΎΡΠΈ ΠΠ΅Π»ΡΠ΄ΡΡΠΌΠ° ΠΌΠΎΠΆΡΡΡ Π΄ΡΠΆΠ΅ ΠΏΠΎΠ²ΡΠ»ΡΠ½ΠΎ Π· Π½ΠΈΠ·ΡΠΊΠΈΠΌΠΈ Π²ΠΈΡ
ΠΎΠ΄Π°ΠΌΠΈ ΠΏΠ΅ΡΠ΅ΡΠ²ΠΎΡΡΠ²Π°ΡΠΈΡΡ Π½Π° ΠΏΡΡΠ°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΡΡΠΈΠ΄ΠΈΠ½-4-ΡΠΏΡΡΠΎΡΠ½Π΄ΠΎΠ»ΡΠ½ΠΎΠ½ΠΈ.ΠΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½Π° ΡΠ°ΡΡΠΈΠ½Π°. ΠΠΈΠΏβΡΡΡΠ½Π½ΡΠΌ Ρ ΠΌΠ΅ΡΠ°Π½ΠΎΠ»Ρ Π΅ΠΊΠ²ΡΠΌΠΎΠ»ΡΠ½ΠΈΡ
ΠΊΡΠ»ΡΠΊΠΎΡΡΠ΅ΠΉ ΡΠ·Π°ΡΠΈΠ½ΡΠ², 5-Π°ΠΌΡΠ½ΠΎΠΏΡΡΠ°Π·ΠΎΠ»ΡΠ² ΡΠ° ΠΊΠΈΡΠ»ΠΎΡΠΈ ΠΠ΅Π»ΡΠ΄ΡΡΠΌΠ° ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΎ ΡΡΠΌΡΡΡ ΠΏΡΡΠ°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΡΡΠΈΠ΄ΠΈΠ½-4-ΡΠΏΡΡΠΎΡΠ½Π΄ΠΎΠ»ΡΠ½ΠΎΠ½ΡΠ² ΡΠ° 3-(5-Π°ΠΌΡΠ½ΠΎΠΏΡΡΠ°Π·ΠΎΠ»-3-ΡΠ»)-3-Π³ΡΠ΄ΡΠΎΠΊΡΠΈ-2-ΠΎΠΊΡΡΠ½Π΄ΠΎΠ»ΡΠ½ΡΠ², ΡΠΊΡ ΡΠΎΠ·Π΄ΡΠ»Π΅Π½Ρ ΠΊΡΠΈΡΡΠ°Π»ΡΠ·Π°ΡΡΡΡ. ΠΠΈΡ
ΡΠ΄ ΡΠΏΡΡΠΎ-ΡΠΏΠΎΠ»ΡΠΊ ΡΠΊΠ»Π°Π΄Π°Ρ 26-82 %, Π° 3-(5-Π°ΠΌΡΠ½ΠΎΠΏΡΡΠ°Π·ΠΎΠ»-3-ΡΠ»)-3-Π³ΡΠ΄ΡΠΎΠΊΡΠΈ-2-ΠΎΠΊΡΡΠ½Π΄ΠΎΠ»ΡΠ½ΡΠ² β 5-23 %. ΠΠ΅ΡΠ΅ΡΠ²ΠΎΡΠ΅Π½Π½Ρ ΠΎΡΡΠ°Π½Π½ΡΡ
Ρ ΠΏΡΠΈΡΡΡΠ½ΠΎΡΡΡ ΠΊΠΈΡΠ»ΠΎΡΠΈ ΠΠ΅Π»ΡΠ΄ΡΡΠΌΠ° Π½Π° ΡΠΏΡΡΠΎ-ΡΠΏΠΎΠ»ΡΠΊΠΈ Π²ΡΠ΄Π±ΡΠ²Π°ΡΡΡΡΡ ΠΏΡΠΈ ΡΡΠΈΠ²Π°Π»ΠΎΠΌΡ ΠΊΠΈΠΏβΡΡΡΠ½Π½Ρ Ρ ΡΠΏΠΈΡΡΠΎΠ²ΠΎΠΌΡ ΡΠ΅ΡΠ΅Π΄ΠΎΠ²ΠΈΡΡ Ρ ΡΡΠΏΡΠΎΠ²ΠΎΠ΄ΠΆΡΡΡΡΡΡ Π²ΠΊΡΠ°ΠΉ Π½ΠΈΠ·ΡΠΊΠΈΠΌΠΈ Π²ΠΈΡ
ΠΎΠ΄Π°ΠΌΠΈ. Π‘ΡΡΡΠΊΡΡΡΡ Ρ ΡΠΊΠ»Π°Π΄ ΡΡΡΡ
ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΈΡ
ΡΠΏΠΎΠ»ΡΠΊ Π΄ΠΎΠ²Π΅Π΄Π΅Π½ΠΎ Π΄Π°Π½ΠΈΠΌΠΈ Π―ΠΠ 1Π, ΠΌΠ°Ρ-ΡΠΏΠ΅ΠΊΡΡΡΠ² Ρ Π΅Π»Π΅ΠΌΠ΅Π½ΡΠ½ΠΈΠΌ Π°Π½Π°Π»ΡΠ·ΠΎΠΌ.ΠΠΈΡΠ½ΠΎΠ²ΠΊΠΈ. ΠΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΠΎ Ρ ΡΡΠΈΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠ½ΠΈΡ
ΡΠ΅Π°ΠΊΡΡΡΡ
ΡΠ·Π°ΡΠΈΠ½ΡΠ², 5-Π°ΠΌΡΠ½ΠΎΠΏΡΡΠ°Π·ΠΎΠ»ΡΠ² Ρ 2,2-Π΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΡΠΎΠΊΡΠ°Π½-4,6-Π΄ΡΠΎΠ½Ρ ΡΠ΅Π°Π»ΡΠ·ΡΡΡΡΡΡ Π΄Π²Π° ΠΊΠΎΠ½ΠΊΡΡΡΡΡΠΈΡ
Π½Π°ΠΏΡΡΠΌΠΊΠΈ Π²Π·Π°ΡΠΌΠΎΠ΄ΡΡ ΡΠ·Π°ΡΠΈΠ½Ρ Π· Π½ΡΠΊΠ»Π΅ΠΎΡΡΠ»Π°ΠΌΠΈ. ΠΠ΄ΠΈΠ½ Π· Π½ΠΈΡ
β Π½ΡΠΊΠ»Π΅ΠΎΡΡΠ»ΡΠ½Π΅ ΠΏΡΠΈΡΠ΄Π½Π°Π½Π½Ρ Π‘4 ΡΠ΅Π°ΠΊΡΡΠΉΠ½ΠΎΠ³ΠΎ ΡΠ΅Π½ΡΡΠ° Π°ΠΌΡΠ½ΠΎΠΏΡΡΠ°Π·ΠΎΠ»Ρ Π΄ΠΎ ΠΊΠ°ΡΠ±ΠΎΠ½ΡΠ»ΡΠ½ΠΎΡ Π³ΡΡΠΏΠΈ ΡΠ·Π°ΡΠΈΠ½Ρ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡΡ Π΄ΠΎ 3-(5-Π°ΠΌΡΠ½ΠΎΠΏΡΡΠ°Π·ΠΎΠ»-4-ΡΠ»)-3-Π³ΡΠ΄ΡΠΎΠΊΡΠΈ-2-ΠΎΠΊΡΡΠ½Π΄ΠΎΠ»ΡΠ½ΡΠ². Π ΡΠ½ΡΠΈΠΉ β ΠΊΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΡΡ ΡΠ·Π°ΡΠΈΠ½Ρ Π· Π΄ΡΠΎΠΊΡΠ°Π½-4,6-Π΄ΡΠΎΠ½ΠΎΠΌ Π·Π° ΠΠ½ΡΠΎΠ²Π΅Π½Π°Π³Π΅Π»Π΅ΠΌ Π·Π°ΠΏΠΎΡΠ°ΡΠΊΠΎΠ²ΡΡ Π΄ΠΎΠΌΡΠ½ΠΎ-ΠΏΡΠΎΡΠ΅Ρ, ΡΠΊΠΈΠΉ Π·Π°Π²Π΅ΡΡΡΡΡΡΡΡ ΡΡΠ²ΠΎΡΠ΅Π½Π½ΡΠΌ ΠΏΠ΅ΡΠ΅Π²Π°ΠΆΠ½ΠΈΡ
ΠΏΡΠΎΠ΄ΡΠΊΡΡΠ² ΡΠ΅Π°ΠΊΡΡΡ β ΠΏΡΡΠ°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΡΡΠΈΠ΄ΠΈΠ½-4-ΡΠΏΡΡΠΎΡΠ½Π΄ΠΎΠ»ΡΠ½ΠΎΠ½ΡΠ²
ΠΠΎΠΌΡΠ½ΠΎ-ΡΠ΅Π°ΠΊΡΡΡ 3-ΠΌΠ΅ΡΠΈΠ»-5-Π°ΠΌΡΠ½ΠΎΠΏΡΡΠ°Π·ΠΎΠ»Ρ Π· 1-ΡΠ΅Π½ΡΠ»-3-(4-Π°Π»ΠΊΠΎΠΊΡΠΈΡΠ΅Π½ΡΠ»)ΠΏΡΡΠ°Π·ΠΎΠ»-4-ΠΊΠ°ΡΠ±Π°Π»ΡΠ΄Π΅Π³ΡΠ΄Π°ΠΌΠΈ ΡΠ° 2,2-Π΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΡΠΎΠΊΡΠ°Π½-4,6-Π΄ΡΠΎΠ½ΠΎΠΌ
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 VilsmeierβHaak 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 VilsmeierβHaack reaction with the yield of 55 β 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 β 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.Π¦Π΅Π»Ρ. Π‘ΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°ΡΡ 1-ΡΠ΅Π½ΠΈΠ»-3-(4-Π°Π»ΠΊΠΎΠΊΡΠΈΡΠ΅Π½ΠΈΠ»)ΠΏΠΈΡΠ°Π·ΠΎΠ»-4-ΠΊΠ°ΡΠ±Π°Π»ΡΠ΄Π΅Π³ΠΈΠ΄Ρ ΠΈ ΡΡΡΠ°Π½ΠΎΠ²ΠΈΡΡ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½Π½ΠΎΡΡΡ ΠΈΡ
Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ Π² ΡΡΠ΅Ρ
ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠ½ΠΎΠΉ ΠΊΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΠΈΠΈ Ρ 3-ΠΌΠ΅ΡΠΈΠ»-5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡΠ°Π·ΠΎΠ»ΠΎΠΌ ΠΈ 2,2-Π΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΠΈΠΎΠΊΡΠ°Π½-4,6-Π΄ΠΈΠΎΠ½ΠΎΠΌ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ ΠΈ ΠΈΡ
ΠΎΠ±ΡΡΠΆΠ΄Π΅Π½ΠΈΠ΅. Π€ΠΎΡΠΌΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π°ΡΠΈΠ»Π³ΠΈΠ΄ΡΠ°Π·ΠΎΠ½ΠΎΠ² ΠΏΠΎ ΠΠΈΠ»ΡΡΠΌΠ΅ΠΉΠ΅ΡΡβΠ₯Π°Π°ΠΊΡ ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½ ΡΡΠ΄ 1-ΡΠ΅Π½ΠΈΠ»-3-(4-Π°Π»ΠΊΠΎΠΊΡΠΈΡΠ΅Π½ΠΈΠ»)ΠΏΠΈΡΠ°Π·ΠΎΠ»-4-ΠΊΠ°ΡΠ±Π°Π»ΡΠ΄Π΅Π³ΠΈΠ΄ΠΎΠ². ΠΠΎΠΌΠΈΠ½ΠΎ-ΡΠ΅Π°ΠΊΡΠΈΠΈ ΡΡΠΈΡ
Π°Π»ΡΠ΄Π΅Π³ΠΈΠ΄ΠΎΠ² Ρ 3-ΠΌΠ΅ΡΠΈΠ»-5-Π°ΠΌΠΈΠ½ΠΎΒΠΏΠΈΡΠ°Π·ΠΎΠ»ΠΎΠΌ ΠΈ 2,2-Π΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΠΈΠΎΠΊΡΠ°Π½-4,6-Π΄ΠΈΠΎΠ½ΠΎΠΌ Π·Π°Π²Π΅ΡΡΠ°ΡΡΡΡ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΏΠΈΡΠ°Π·ΠΎΠ»ΠΎ[3,4-b]-ΠΏΠΈΡΠΈΠ΄ΠΎΠ½ΠΎΠ²ΡΡ
ΡΠΈΡΡΠ΅ΠΌ.ΠΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½Π°Ρ ΡΠ°ΡΡΡ. Π‘ΠΈΠ½ΡΠ΅Π· 1-ΡΠ΅Π½ΠΈΠ»-3-(4-Π°Π»ΠΊΠΎΠΊΡΠΈΡΠ΅Π½ΠΈΠ»)ΒΠΏΠΈΡΠ°ΒΠ·ΠΎΠ»-4-ΠΊΠ°ΡΠ±Π°Π»ΡΠ΄Π΅Π³ΠΈΠ΄ΠΎΠ² ΠΎΡΡΡΠ΅ΡΡΠ²Π»Π΅Π½Β ΡΠΎΡΠΌΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π°ΡΠΈΠ»Π³ΠΈΠ΄ΡΠ°Π·ΠΎΠ½ΠΎΠ² Π² ΡΡΠ»ΠΎΠ²ΠΈΡΡ
ΡΠ΅Π°ΠΊΡΠΈΠΈ ΠΠΈΠ»ΡΡΠΌΠ΅ΠΉΠ΅ΡΠ°βΠ₯Π°Π°ΠΊΠ° Ρ Π²ΡΡ
ΠΎΠ΄ΠΎΠΌ 55 β 88 %. ΠΠΈΠΏΡΡΠ΅Π½ΠΈΠ΅ΠΌ Π² 2-ΠΏΡΠΎΠΏΠ°Π½ΠΎΠ»Π΅ ΡΠΊΠ²ΠΈΠΌΠΎΠ»ΡΡΠ½ΡΡ
ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ² ΡΡΠΈΡ
Π°Π»ΡΠ΄Π΅Π³ΠΈΠ΄ΠΎΠ², 3-ΠΌΠ΅ΡΠΈΠ»-5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡΠ°Π·ΠΎΠ»Π° ΠΈ 2,2-Π΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΠΈΠΎΠΊΡΠ°Π½-4,6-Π΄ΠΈΠΎΠ½Π° ΠΏΠΎΠ»ΡΡΠ΅Π½Ρ 3-ΠΌΠ΅ΡΠΈΠ»-4-(1β²,3β²-Π΄ΠΈΠ°ΡΠΈΠ»ΠΏΠΈΡΠ°Π·ΠΎΠ»-4β²-ΠΈΠ»)ΡΠ΅ΡΡΠ°Π³ΠΈΠ΄ΡΠΎΠΏΠΈΡΠ°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΠΈΡΠΈΠ΄ΠΈΠ½-6-ΠΎΠ½Ρ. ΠΡΡ
ΠΎΠ΄ ΡΠ΅Π»Π΅Π²ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ β 48 β 75 %. Π‘ΡΡΠΎΠ΅Π½ΠΈΠ΅ ΠΈ ΡΠΎΡΡΠ°Π² Π²ΡΠ΅Ρ
ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π²Π΅ΡΠ΅ΡΡΠ² Π΄ΠΎΠΊΠ°Π·Π°Π½Ρ Π΄Π°Π½Π½ΡΠΌΠΈ 1Π Π―ΠΠ -, ΠΠ-ΡΠΏΠ΅ΠΊΡΡΠΎΠ² ΠΈ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠ½ΡΠΌ Π°Π½Π°Π»ΠΈΠ·ΠΎΠΌ.ΠΡΠ²ΠΎΠ΄Ρ. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ ΡΠ΅Π°ΠΊΡΠΈΠΈ 1,3-Π΄ΠΈΠ°ΡΠΈΠ»Π·Π°ΠΌΠ΅ΡΠ΅Π½Π½ΡΡ
ΠΏΠΈΡΠ°Π·ΠΎΠ»-4-ΠΊΠ°ΡΠ±Π°Π»ΡΠ΄Π΅Π³ΠΈΠ΄ΠΎΠ² Ρ 3-ΠΌΠ΅ΡΠΈΠ»- 5-Π°ΠΌΠΈΠ½ΠΎΠΏΠΈΡΠ°Π·ΠΎΠ»ΠΎΠΌ ΠΈ 2,2βΠ΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΠΈΠΎΠΊΡΠ°Π½-4,6-Π΄ΠΈΠΎΠ½ΠΎΠΌ ΡΠ΅Π³ΠΈΠΎΡΠ΅Π»Π΅ΠΊΡΠΈΠ²Π½Ρ ΠΈ Π·Π°Π²Π΅ΡΡΠ°ΡΡΡΡ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ 3,4-ΠΏΠΈΡΠ°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΠΈΡΠΈΠ΄ΠΎΠ½ΠΎΠ²ΡΡ
ΡΠΈΡΡΠ΅ΠΌ. Π’Π°ΠΊΠ°Ρ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½Π½ΠΎΡΡΡ ΠΏΡΠΎΡΠ΅ΡΡΠ° ΠΎΡΠ²Π΅ΡΠ°Π΅Ρ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ Ξ²-ΡΠ³Π»Π΅ΡΠΎΠ΄Π½ΠΎΠ³ΠΎ Π°ΡΠΎΠΌΠ° Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠ³ΠΎ ΠΈΠ½ΡΠ΅ΡΠΌΠ΅Π΄ΠΈΠ°ΡΠ°, ΠΎΠ±ΡΠ°Π·ΡΡΡΠ΅Π³ΠΎΡΡ Π½Π° ΠΏΠ΅ΡΠ²ΠΎΠΉ ΡΡΠ°Π΄ΠΈΠΈ ΠΈΠ· Π΄ΠΈΠΎΠΊΡΠ°Π½Π΄ΠΈΠΎΠ½Π° ΠΈ Π°Π»ΡΠ΄Π΅Π³ΠΈΠ΄Π°, Ρ ΡΠ³Π»Π΅ΡΠΎΠ΄Π½ΡΠΌ Π½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ»ΡΠ½ΡΠΌ ΡΠ΅Π½ΡΡΠΎΠΌ Π² ΠΌΠΎΠ»Π΅ΠΊΡΠ»Π΅ Π°ΠΌΠΈΠ½ΠΎΠ°Π·ΠΎΠ»Π°, Π° Π°ΡΠΎΠΌΠ° ΡΠ³Π»Π΅ΡΠΎΠ΄Π° Π‘=Π Π³ΡΡΠΏΠΏΡ Π΄ΠΈΠΎΠΊΡΠ°Π½-4,6-Π΄ΠΈΠΎΠ½Π° β Ρ ΡΠΊΠ·ΠΎΡΠΈΠΊΠ»ΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΌΠΈΠ½ΠΎΠ³ΡΡΠΏΠΏΠΎΠΉ Π³Π΅ΡΠ΅ΡΠΈΠ»Π°ΠΌΠΈΠ½Π°.Β Received: 13.01.2019Revised: 31.01.2020Accepted: 27.02.2020ΠΠ΅ΡΠ°. Π‘ΠΈΠ½ΡΠ΅Π·ΡΠ²Π°ΡΠΈ 1-ΡΠ΅Π½ΡΠ»-3-(4-Π°Π»ΠΊΠΎΠΊΡΠΈΡΠ΅Π½ΡΠ»)ΠΏΡΡΠ°Π·ΠΎΠ»-4-ΠΊΠ°ΡΠ±Π°Π»ΡΠ΄Π΅Π³ΡΠ΄ΠΈ Ρ Π²ΡΡΠ°Π½ΠΎΠ²ΠΈΡΠΈ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΡΡΡΡ ΡΡ
Π²Π·Π°ΡΠΌΠΎΠ΄ΡΡ Ρ ΡΡΠΈΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠ½ΡΠΉ ΠΊΠΎΠ½Π΄Π΅Π½ΡΠ°ΡΡΡ Π· 3-ΠΌΠ΅ΡΠΈΠ»-5-Π°ΠΌΡΠ½ΠΎΠΏΡΡΠ°Π·ΠΎΠ»ΠΎΠΌ ΡΠ° 2,2-Π΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΡΠΎΠΊΡΠ°Π½-4,6-Π΄ΡΠΎΠ½ΠΎΠΌ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΠΈ ΡΠ° ΡΡ
ΠΎΠ±Π³ΠΎΠ²ΠΎΡΠ΅Π½Π½Ρ. Π‘ΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΎ ΡΡΠ΄ 1-ΡΠ΅Π½ΡΠ»-3-(4-Π°Π»ΠΊΠΎΠΊΡΠΈΡΠ΅Π½ΡΠ»)ΠΏΡΡΠ°Π·ΠΎΠ»-4-ΠΊΠ°ΡΠ±Π°Π»ΡΠ΄Π΅Π³ΡΠ΄ΡΠ² ΡΠΎΡΠΌΡΠ»ΡΠ²Π°Π½Π½ΡΠΌ Π°ΡΠΈΠ»Π³ΡΠ΄ΡΠ°Π·ΠΎΠ½ΡΠ² Π·Π° ΠΡΠ»ΡΡΠΌΠ΅ΠΉΠ΅ΡΠΎΠΌβΠ₯Π°Π°ΠΊΠΎΠΌ. ΠΠΎΠΌΡΠ½ΠΎ-ΡΠ΅Π°ΠΊΡΡΡ ΡΠΈΡ
Π°Π»ΡΠ΄Π΅Π³ΡΠ΄ΡΠ² Π· 3-ΠΌΠ΅ΡΠΈΠ»-5-Π°ΠΌΡΠ½ΠΎΠΏΡΡΠ°Π·ΠΎΠ»ΠΎΠΌ ΡΠ° 2,2-Π΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΡΠΎΠΊΡΠ°Π½-4,6-Π΄ΡΠΎΠ½ΠΎΠΌ Π·Π°Π²Π΅ΡΡΡΡΡΡΡΡ ΡΡΠ²ΠΎΡΠ΅Π½Π½ΡΠΌ ΠΏΡΡΠ°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΡΡΠΈΠ΄ΠΎΠ½ΠΎΠ²ΠΈΡ
ΡΠΈΡΡΠ΅ΠΌ.ΠΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½Π° ΡΠ°ΡΡΠΈΠ½Π°. Π‘ΠΈΠ½ΡΠ΅Π· 1-ΡΠ΅Π½ΡΠ»-3-(4-Π°Π»ΠΊΠΎΠΊΡΠΈΡΠ΅Π½ΡΠ»)ΠΏΡΡΠ°Π·ΠΎΠ»-4-ΠΊΠ°ΡΠ±Π°Π»ΡΠ΄Π΅Π³ΡΠ΄ΡΠ² Π·Π΄ΡΠΉΡΠ½Π΅Π½ΠΎ ΡΠΎΡΠΌΡΠ»ΡΠ²Π°Π½Π½ΡΠΌ Π°ΡΠΈΠ»Π³ΡΠ΄ΡΠ°Π·ΠΎΠ½ΡΠ² Π² ΡΠΌΠΎΠ²Π°Ρ
ΡΠ΅Π°ΠΊΡΡΡ ΠΡΠ»ΡΡΠΌΠ΅ΠΉΠ΅ΡΠ°βΠ₯Π°Π°ΠΊΠ° Π· Π²ΠΈΡ
ΠΎΠ΄ΠΎΠΌ 55β
ββ
88 %. ΠΠΈΠΏβΡΡΡΠ½Π½ΡΠΌ Ρ 2-ΠΏΡΠΎΠΏΠ°Π½ΠΎΠ»Ρ ΡΡΠΌΡΡΡ Π΅ΠΊΠ²ΡΠΌΠΎΠ»ΡΠ½ΠΈΡ
ΠΊΡΠ»ΡΠΊΠΎΡΡΠ΅ΠΉ ΡΠΈΡ
Π°Π»ΡΠ΄Π΅Π³ΡΠ΄ΡΠ², 3-ΠΌΠ΅ΡΠΈΠ»-5-Π°ΠΌΡΠ½ΠΎΠΏΡΡΠ°Π·ΠΎΠ»Ρ ΡΠ° 2,2-Π΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΡΠΎΠΊΡΠ°Π½-4,6-Π΄ΡΠΎΠ½Ρ ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΎ 3-ΠΌΠ΅ΡΠΈΠ»-4-(1',3'-Π΄ΡΠ°ΡΠΈΠ»ΠΏΡΡΠ°Π·ΠΎΠ»-4'-ΡΠ»)ΡΠ΅ΡΡΠ°Π³ΡΠ΄ΡΠΎΠΏΡΡΠ°Π·ΠΎΠ»ΠΎ[3,4-b]ΠΏΡΡΠΈΠ΄ΠΈΠ½-6-ΠΎΠ½ΠΈ. ΠΠΈΡ
ΡΠ΄ ΡΡΠ»ΡΠΎΠ²ΠΈΡ
ΡΠΏΠΎΠ»ΡΠΊ β 48β
ββ
75 %. Π‘ΡΡΡΠΊΡΡΡΡ Ρ ΡΠΊΠ»Π°Π΄ ΡΡΡΡ
ΡΠΈΠ½ΡΠ΅Π·ΠΎΠ²Π°Π½ΠΈΡ
ΡΠ΅ΡΠΎΠ²ΠΈΠ½ Π΄ΠΎΠ²Π΅Π΄Π΅Π½ΠΎ Π΄Π°Π½ΠΈΠΌΠΈ 1Π Π―ΠΠ -, ΠΠ§-ΡΠΏΠ΅ΠΊΡΡΡΠ² ΡΠ° Π΅Π»Π΅ΠΌΠ΅Π½ΡΠ½ΠΈΠΌ Π°Π½Π°Π»ΡΠ·ΠΎΠΌ.ΠΠΈΡΠ½ΠΎΠ²ΠΊΠΈ. ΠΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΠΎ ΡΠ΅Π°ΠΊΡΡΡ 1,3-Π΄ΡΠ°ΡΠΈΠ»Π·Π°ΠΌΡΡΠ΅Π½ΠΈΡ
ΠΏΡΡΠ°Π·ΠΎΠ»-4-ΠΊΠ°ΡΠ±Π°Π»ΡΠ΄Π΅Π³ΡΠ΄ΡΠ² Π· 3-ΠΌΠ΅ΡΠΈΠ»-5-Π°ΠΌΡΠ½ΠΎΠΏΡΡΠ°Π·ΠΎΠ»ΠΎΠΌ ΡΠ° 2,2βΠ΄ΠΈΠΌΠ΅ΡΠΈΠ»-1,3-Π΄ΡΠΎΠΊΡΠ°Π½-4,6-Π΄ΡΠΎΠ½ΠΎΠΌ Ρ ΡΠ΅Π³ΡΠΎΡΠ΅Π»Π΅ΠΊΡΠΈΠ²Π½ΠΈΠΌΠΈ Ρ Π·Π°Π²Π΅ΡΡΡΡΡΡΡΡ ΡΡΠ²ΠΎΡΠ΅Π½Π½ΡΠΌ Π²ΠΈΠΊΠ»ΡΡΠ½ΠΎ 3,4-ΠΏΡΡΠ°Π·ΠΎΠ»ΠΎ[3,4-b]-ΠΏΡΡΠΈΠ΄ΠΈΠ½-6-ΠΎΠ½ΠΎΠ²ΠΈΡ
ΡΠΈΡΡΠ΅ΠΌ. Π’Π°ΠΊΠ° Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½ΡΡΡΡ ΠΏΡΠΎΡΠ΅ΡΡ Π²ΡΠ΄ΠΏΠΎΠ²ΡΠ΄Π°Ρ Π²Π·Π°ΡΠΌΠΎΠ΄ΡΡ Ξ²-Π²ΡΠ³Π»Π΅ΡΠ΅Π²ΠΎΠ³ΠΎ Π°ΡΠΎΠΌΠ° ΠΉΠΌΠΎΠ²ΡΡΠ½ΠΎΠ³ΠΎ ΡΠ½ΡΠ΅ΡΠΌΠ΅Π΄ΡΠ°ΡΡ, ΡΠΊΠΈΠΉ ΡΡΠ²ΠΎΡΡΡΡΡΡΡ Π½Π° ΠΏΠ΅ΡΡΡΠΉ ΡΡΠ°Π΄ΡΡ Π· Π΄ΡΠΎΠΊΡΠ°Π½Π΄ΡΠΎΠ½Ρ ΡΠ° Π°Π»ΡΠ΄Π΅Π³ΡΠ΄Ρ, Π· Π²ΡΠ³Π»Π΅ΡΠ΅Π²ΠΈΠΌ Π½ΡΠΊΠ»Π΅ΠΎΡΡΠ»ΡΠ½ΠΈΠΌ ΡΠ΅Π½ΡΡΠΎΠΌ Ρ ΠΌΠΎΠ»Π΅ΠΊΡΠ»Ρ Π°ΠΌΡΠ½ΠΎΠ°Π·ΠΎΠ»Ρ, Π° Π°ΡΠΎΠΌΠ° Π²ΡΠ³Π»Π΅ΡΡ Π‘=Π Π³ΡΡΠΏΠΈ Π΄ΡΠΎΠΊΡΠ°Π½-4,6-Π΄ΡΠΎΠ½Ρ β Π· Π΅ΠΊΠ·ΠΎΡΠΈΠΊΠ»ΡΡΠ½ΠΎΡ Π°ΠΌΡΠ½ΠΎΠ³ΡΡΠΏΠΎΡ Π³Π΅ΡΠ΅ΡΠΈΠ»Π°ΠΌΡΠ½Ρ.Β Received: 13.01.2019Revised: 31.01.2020Accepted: 27.02.202
Transcriptional Regulation of VEGF-A by the Unfolded Protein Response Pathway
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
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
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
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 βmorphological communicationβ, 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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