Isoandrographolide photoaffinity labeling molecular probe, preparation method and pharmaceutical composition of molecular probe

A technology of andrographolide and marker molecule, which can be used in drug combinations, medical preparations containing active ingredients, antipyretics, etc., and can solve the problem that the mechanism of action of the target protein is not fully elucidated.

Inactive Publication Date: 2014-01-29
XIAMEN JSY PHARMA TECH CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Our study found that isoandrographolide has a bidirectional regulatory effect on the activation and functional status of macrophages, at least partly through

Method used

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  • Isoandrographolide photoaffinity labeling molecular probe, preparation method and pharmaceutical composition of molecular probe
  • Isoandrographolide photoaffinity labeling molecular probe, preparation method and pharmaceutical composition of molecular probe
  • Isoandrographolide photoaffinity labeling molecular probe, preparation method and pharmaceutical composition of molecular probe

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Preparation of isoandrographolide II

[0044] Dissolve 5.0 g of andrographolide in 80 mL of concentrated hydrochloric acid, stir magnetically at room temperature until completely dissolved, and place overnight. After the reaction was completed, the reaction solution was poured into a beaker filled with ice-cold 200 mL saturated saline solution, and a saturated sodium carbonate solution was slowly added with stirring until the pH was about 7.0. Extracted with ethyl acetate (100 mL×8), washed with saturated brine (100 mL×3), dried over anhydrous sodium sulfate, concentrated by filtration, and the crude product was recrystallized from absolute ethanol to obtain 3.0 g of white solid, yield 60%. 1 H-NMR (CDCl 3 , 400MHz) δ: 7.29 (1H, overlapped signal, H-14), 4.82 (2H, s, H-15), 4.71 (1H, t, J=20.0Hz, H-12), 4.27 (1H, d, J=12.0Hz, H-19a), 3.47(1H, dd, J=4.0Hz, 8.0Hz, H-3), 3.38(1H, d, J=12.0Hz, H-19b), 2.48~2.42(4H , -OH, 11), 2.25~2.19(2H, 7a, 9), 2.07~1.99(1H, H-7b), 1....

Embodiment 2

[0046] Compound III 1 preparation of

[0047] 1.0g II was dissolved in 130mL dichloromethane, and 0.515g K was added 2 CO 3 , stirred magnetically at room temperature for 30 min, then slowly added 0.638 g of bromoacetyl bromide dropwise, and reacted at room temperature for 3 h. After the reaction was completed, it was washed with saturated brine (50mL×3), dried over anhydrous magnesium sulfate, and separated by silica gel column chromatography (V 石油醚 :V 乙酸乙酯 =1:1), to obtain 1.145g compound III 1 , yield 85%. 1 H-NMR (CDCl 3 , 400MHz) δ: 7.29 (1H, overlapped signal, H-14), 4.83 (2H, s, H-15), 4.73 (1H, t, J=20.0Hz, H-12), 4.56 (1H, d, J = 12.0Hz, H-19a), 4.26 (1H, d, J = 12.0Hz, H-19b), 3.86 (2H, s, 19-CO CH 2 Br), 3.36 (1H, dd, J=8.0Hz, 4.0Hz, H-3), 2.51~2.45 (1H, H-11a), 2.26~2.19 (5H, -OH, 7a, 9, 11b), 2.08 ~2.02(1H, H-7b), 1.83~1.50(7H, H-1, 2, 5, 6), 1.23(3H, s, H-17), 1.13(3H, overlapped-signal, H-18) , 1.00 (3H, overlapped-signal, H-20).

[0048] Compound II...

Embodiment 3

[0057] Compound V 1 preparation of

[0058] 0.5 g compound III 1 Dissolve in 50mL acetone, add 0.2g K 2 CO 3 , stirred magnetically at room temperature for 30 min, then gradually added 0.31 g of photoaffinity labeling group IV, and stirred magnetically at room temperature for 4 h. After the reaction is complete, pour the reaction solution into a beaker containing 100 mL of saturated sodium bicarbonate solution, extract with dichloromethane (100 mL×3), and then use saturated sodium bicarbonate solution (100 mL×3), saturated saline (100 mL×3 ) washing, dried over anhydrous magnesium sulfate, separated by silica gel column chromatography (V 石油醚 :V 乙酸乙酯 =1:1), to obtain 0.610g compound V 1 , yield 91%. 1 H-NMR (CDCl 3 , 400MHz) δ: 8.17 (2H, d, J = 8.0Hz, ph), 7.76 (2H, d, J = 8.0Hz, ph), 7.69 (2H, d, J = 8.0Hz, ph), 7.27 (1H , overlapped-signal, H-14), 6.68 (2H, d, J=8.0Hz, ph), 4.88 (2H, d, J=2.5Hz, 19-CO CH 2 ), 4.79 (2H, s, H-15), 4.69 (1H, t, J=16.0Hz, H-12), 4.61 (...

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Abstract

The invention discloses an isoandrographolide photoaffinity labeling molecular probe. The structure of the molecular probe is represented in a formula (I), wherein n1 ranges from 1 to 5 and n2 ranges from 0 to 2. Furthermore, the invention discloses a preparation and a pharmaceutical composition of the isoandrographolide photoaffinity labeling molecular probe. The compound, which is excellent in TNF-alpha inhibitory activity, can be used for researching and discovering target protein of isoandrographolide having an action of regulating macrophage function, and the compound, as a tool medicine, can be used for medicine development of a diagnostic reagent of the target protein as well as a regulator thereof.

Description

technical field [0001] The invention relates to a photoaffinity labeling molecular probe of isoandrographolide, their synthesis method, and a pharmaceutical composition containing them. technical background [0002] In recent decades, due to the cross-infiltration of computer science, life science, chemistry and other disciplines, the mode and method of new drug research and development have also undergone tremendous changes, resulting in a series of new theories, methods and technologies. The discovery of innovative drugs today is increasingly dependent on the discovery of targets and the determination of the mode of action of targets and active compounds. However, current biotechnology at the genetic level cannot resolve which protein is the target of a small molecule drug for a certain disease. Therefore, the technical focus of drug discovery research has shifted from the genome to the proteome. The small molecule probe labeling technology developed in recent decades has...

Claims

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Application Information

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IPC IPC(8): C07D407/04A61K31/365G01N33/52A61P29/00A61P37/02
CPCC07D307/92G01N33/6872G01N33/94
Inventor 李晶杨超张雷
Owner XIAMEN JSY PHARMA TECH CO LTD
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