PL195740B1 - Novel leading structure of isoxazole derivative - Google Patents

Novel leading structure of isoxazole derivative

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Publication number
PL195740B1
PL195740B1 PL343052A PL34305200A PL195740B1 PL 195740 B1 PL195740 B1 PL 195740B1 PL 343052 A PL343052 A PL 343052A PL 34305200 A PL34305200 A PL 34305200A PL 195740 B1 PL195740 B1 PL 195740B1
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PL
Poland
Prior art keywords
isoxazole
isoxazole derivative
leading structure
amino
novel leading
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PL343052A
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Polish (pl)
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PL343052A1 (en
Inventor
Stanisław Ryng
Michał Zimecki
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Akademia Medyczna Im Piastow S
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Application filed by Akademia Medyczna Im Piastow S filed Critical Akademia Medyczna Im Piastow S
Priority to PL343052A priority Critical patent/PL195740B1/en
Publication of PL343052A1 publication Critical patent/PL343052A1/en
Publication of PL195740B1 publication Critical patent/PL195740B1/en

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  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

Nowa struktura wiodąca pochodnej izoksazolu o nazwie 5-amino-3-metylo-4-(2,5-dimetylopiroloaminokarbonylo)-izoksazol i wzorze przedstawionym na rysunku.A new leading structure of an isoxazole derivative named 5-amino-3-methyl-4-(2,5-dimethylpyrroleaminocarbonyl)-isoxazole and with the formula shown in the figure.

Description

Przedmiotem wynalazku jest nowa struktura wiodąca pochodnej izoksazolu o nazwie 5-amino-3-metylo-4-(2,5-dimetylopiroloaminokarbonylo)-izoksazol i wzorze przedstawionym na rysunku, wykazująca oddziaływanie biologiczne o aktywności immunotropowej.The subject of the invention is a new leading structure of an isoxazole derivative called 5-amino-3-methyl-4-(2,5-dimethylpyrroleaminocarbonyl)-isoxazole and with the formula shown in the drawing, demonstrating biological activity with immunotropic activity.

Wynalazek dotyczy nowej struktury wiodącej pochodnej izoksazolu o nazwie 5-amino-3-metylo-4-(2,5-dimetylopiroloaminokarbonylo)-izoksazol i wzorze przedstawionym na rysunku.The invention relates to a new structure of the leading isoxazole derivative named 5-amino-3-methyl-4-(2,5-dimethylpyrroleaminocarbonyl)-isoxazole and the formula shown in the drawing.

Nową pochodną otrzymuje się w reakcji hydrazydu kwasu 5-amino-3-metyloizoksazolo-4-karboksylowego (V) z heksadionem-2,5, w obecności izopropanolu.The new derivative is obtained by the reaction of 5-amino-3-methylisoxazole-4-carboxylic acid hydrazide (V) with hexadione-2,5 in the presence of isopropanol.

Podczas badań nieoczekiwanie okazało się, że nowy związek wykazuje aktywność immunotropową porównywalną z Cyklosporyną A (CSA). W dwu testach produkcji znaczących cytokin: TNF-a oraz Interleukiny-6 (IL-6) stwierdzono znaczące oddziaływanie biologiczne, które przedstawia poniższe zestawienie.During the study, it was unexpectedly revealed that the new compound exhibited immunotropic activity comparable to Cyclosporine A (CSA). Two assays for the production of significant cytokines: TNF-α and Interleukin-6 (IL-6) demonstrated significant biological effects, as summarized below.

Związek Relationship Dawka μg/mlDose μg/ml TNF-a pg/ml TNF-a pg/ml IL-6 pg/ml IL-6 pg/ml RozpuszczalnikSolvent 6128 6128 648 648 Cremophor/etanolCremophor/ethanol 6050 6050 622 622 CsA CsA 1 1 5762 5762 672 672 5 5 1661 1661 684 684 Związek badany Compound tested 1 1 2897 2897 717 717 5 5 1776 1776 951 951

Sposób otrzymywania nowego 5-amino-3-metylo-4-(2,5-dimetylopirolo-aminokarbonylo)-izoksazolu przedstawia przykład wykonania.The method for obtaining the new 5-amino-3-methyl-4-(2,5-dimethylpyrrole-aminocarbonyl)-isoxazole is presented in the following embodiment.

Porcję 3 mmoli hydrazydu kwasu 5-amino-3-metyloizoksazolo-4-karboksylo-wego umieszcza się w kolbie okrągłodennej o pojemności 100 mL, zaopatrzonej w chłodnicę zwrotną i mieszadełko, a następnie dodaje się 50 mL izopropanolu i 3,3 mmoli heksadionu-2,5. Całość miesza się na mieszadle magnetycznym i ogrzewa do temperatury wrzenia w ciągu 10 minut. Mieszaninę reakcyjną utrzymuje się we wrzeniu przez następne 7 godzin. Po zakończeniu procesu, kontrolowanym na płytkach TLC, zawiesinę ochładza się, po czym odsącza. Surowy produkt przekrystalizowuje się z etanolu, otrzymując biały, krystaliczny produkt z wydajnością 49,3% wydajności teoretycznej, o temperaturze topnienia 224-225 C.A 3 mmol portion of 5-amino-3-methylisoxazole-4-carboxylic acid hydrazide was placed in a 100 mL round-bottomed flask equipped with a reflux condenser and a stirrer bar, followed by the addition of 50 mL of isopropanol and 3.3 mmol of 2,5-hexadione. The mixture was stirred on a magnetic stirrer and heated to reflux for 10 minutes. The reaction mixture was heated at reflux for another 7 hours. After completion of the reaction, as monitored by TLC plates, the suspension was cooled and filtered. The crude product was recrystallized from ethanol to give a white crystalline product in 49.3% of theory, melting at 224-225°C.

Analizę nowej pochodnej przeprowadzono następująco.The analysis of the new derivative was performed as follows.

Temperatury topnienia oznaczono na aparacie Boethiusa i nie korygowano.Melting points were determined on the Boethius apparatus and are uncorrected.

Widma IR mierzono w KBr na aparacie Specord M-80.IR spectra were measured in KBr on a Specord M-80 instrument.

Widma 1H NMR oznaczono na aparacie Tesla 80 MHz. Przesunięcia chemiczne oznaczono wobec tetrametylosilanu (TMS) jako zewnętrznego standardu.1H NMR spectra were determined on an 80 MHz Tesla instrument. Chemical shifts were determined against tetramethylsilane (TMS) as an external standard.

Widma MS mierzono na spektrometrze LKB 9000.MS spectra were measured on an LKB 9000 spectrometer.

Wszystkie związki analizowano na zawartość (%) C, H, N. Różnice pomiędzy wartościami, obliczoną i znalezioną, nie przekraczały ± 0,3%.All compounds were analyzed for the content (%) of C, H, N. The differences between the calculated and found values did not exceed ± 0.3%.

Wartości wyznaczone są następujące:The values determined are as follows:

IR (KBr)vc=ocm-1 1712 c=oIR (KBr)vc=ocm -1 1712 c=o

1H NMR(DMSO-d6)/TMS d, J (Hz): 2,1 (s, 6H, 2CH-pirol); 2,4 (s, 3H, CH3-izoksazol); 5 7 (s, 2H, -NH2); 7,6 (s, 2H, 2CH-pirol); 9,7 (s, 1H, NH)1H NMR(DMSO-d6)/TMS d, J (Hz): 2.1 (s, 6H, 2CH-pyrrole); 2.4 (s, 3H, CH3-isoxazole); 5 7 (s, 2H, -NH2); 7.6 (s, 2H, 2CH-pyrrole); 9.7 (s, 1H, NH)

MS(70 eV),m/z(%) 233,0.MS(70 eV),m/z(%) 233.0.

Claims (1)

Nowa struktura wiodąca pochodnej izoksazolu o nazwie 5-amino-3-me-tylo-4-(2,5-dimetylopiroloaminokarbonylo)-izoksazol i wzorze przedstawionym na rysunku.The new head structure of isoxazole derivative named 5-amino-3-methyl-4- (2,5-dimethylpyrrolaminocarbonyl) -isoxazole and the formula shown in the figure.
PL343052A 2000-10-06 2000-10-06 Novel leading structure of isoxazole derivative PL195740B1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PL343052A PL195740B1 (en) 2000-10-06 2000-10-06 Novel leading structure of isoxazole derivative

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PL343052A PL195740B1 (en) 2000-10-06 2000-10-06 Novel leading structure of isoxazole derivative

Publications (2)

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PL343052A1 PL343052A1 (en) 2002-04-08
PL195740B1 true PL195740B1 (en) 2007-10-31

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