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Simplified structure of three asprosin, its preparation method, its pharmaceutical composition and use

A compound and halogen technology, applied in the field of medicine, can solve problems such as limited sources, complex structures of natural products, and difficult preparations, and achieve excellent results

Active Publication Date: 2016-03-09
INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

And it also has strong inhibitory activity to various hypoxia-induced CDKN1A, VEGF and GLUT-1 genes (J.Nat.Prod., 2004,67,767-771; Biochem.Biophy.Res.Commun., 2005,333 , 1026-1033.), but this type is difficult to extract and separate, so the sources are limited
In addition, the structure of natural products is complex, and it is difficult to prepare by synthetic methods.

Method used

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  • Simplified structure of three asprosin, its preparation method, its pharmaceutical composition and use
  • Simplified structure of three asprosin, its preparation method, its pharmaceutical composition and use
  • Simplified structure of three asprosin, its preparation method, its pharmaceutical composition and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0081] Step A: Add o-methoxyphenol 10g (80.56mmol), sodium hydroxide 5.76g (144mmol), methanol 100mL in a 250mL round bottom flask, add elemental iodine 20.4g (80.3mmol) at -4°C, and at this temperature After reacting for 1 hour, TLC showed that it was complete. Stop the reaction, pour into water, extract with ethyl acetate, wash with sodium dithionite, wash with saturated sodium chloride, dry with anhydrous sodium sulfate, filter, evaporate the solvent, and obtain 10.6 g of the crude product on a silica gel short column. rate 53%

[0082]

[0083] 1 HNMR (300M, CDCl 3 , δppm) 7.18 (d, 1H, J=8.4Hz, Ar-H), 6.86 (s, 1H, Ar-H), 6.69 (d, 1H, J=

[0084] 8.1Hz, Ar-H), 5.57(s, 1H, OH) 3.88(s, 1H, -OCH 3 )

[0085] Step B: 110.6g (42.4mmol) of compound was added to a 200mL round bottom flask, dissolved in 50mL of anhydrous DMF, 22g (159mmol) of anhydrous potassium carbonate was added, and 1.39mL (42.4mmol) of benzyl bromide was slowly added dropwise under ice bath, rt After 2...

experiment example 1

[0153] Experimental example 1. Inhibitory effect of triasprosin-8 and its derivatives on HIF-1 activity

[0154] (1) Method

[0155] Report gene assay

[0156] The T47D cell model transiently co-transfected with pGL2-TK-3HRE / pRL-CMV plasmid was used for detection. pGL2-TK-3HRE is a firefly luciferase plasmid containing HRE (HIF-1 binding response element), and pRL-CMV is a Renilla luciferase plasmid. Under hypoxic conditions, pGL2-TK-3HRE highly expressed firefly luciferase in cells, but pRL-CMV was not affected.

[0157] 1. Human breast cancer cells T47D (ATCC) use RPMI-1640 containing 10% FBS, penicillin (100IU / ml), streptomycin (100g / ml) in normal oxygen 21% O 2 , 5%CO 2 cultured under conditions. T47D cells were seeded in 96-well plate, 45000 cells / well, 21% O 2 , 5%CO 2After 48 hours of culture, the fusion degree is about 90-95%. Apply lipofectamine2000 for transient co-transfection, add 0.5 μl lipo2000 to each well, pGL2-TK-3HRE, pRL-CMV respectively 0.2 μg, 0.01 ...

experiment example 2、 3

[0172] Experimental Example 2. Inhibitory Effect of Triasprosin-8 and Its Derivatives on Tumor Cell Growth under Normal Oxygen Conditions

[0173] (1) Method

[0174] Determination of Inhibitory Effects of Triasprosin and Its Derivatives on Tumor Cell Growth by MTT Method

[0175] Digest the cells in the logarithmic growth phase with 0.25% trypsin-EDTA, prepare a single-cell suspension with a certain concentration, and inoculate 100-2000 cells / well in a 96-well plate according to the difference in cell growth rate, each well Add 100 μL of cell suspension. After 24 hours, add fresh medium containing different concentrations of compounds and corresponding solvent controls, add 100 μL to each well (DMSO final concentration 50 .

[0176] Inhibition rate (%)=(average OD value of the control group-average OD value of the administration group) / average OD value of the control group×100%

[0177] (2) Results

[0178] Table 4. Inhibitory effect of triasprosin-8 on tumor cell growth ...

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PUM

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Abstract

Disclosed a saucernetin structurally simplified substance and the preparation method and pharmaceutical composition and use thereof. In particular, it relates to a compound of general formula (I) shown as formula (I) or an isomer thereof and a salt thereof, and the preparation method for such compounds. A novel pharmaceutical composition contains an effective amount of compound of formula I and a pharmacodynamically acceptable vector. The present invention also discloses the use of such compounds in preparing drugs for preventing and / or treating tumours. The tumours include neural glioblastoma, melanoma, gastric cancer, lung cancer, breast cancer, kidney cancer, liver cancer, oral epidermoid carcinoma, cervical cancer, ovarian cancer, pancreatic cancer, prostate cancer, and colon cancer and rectal adenocarcinoma.

Description

technical field [0001] The invention relates to a novel triasprosin structural simplification, a preparation method thereof, a pharmaceutical composition containing them, and its use as a medicine, especially as an antitumor medicine, belonging to the technical field of medicine. Background technique [0002] At present, it is believed that due to the structural and functional abnormalities of the blood vessels of most solid tumors, they cannot meet the needs of nutrients and oxygen for the rapid growth of tumor cells, resulting in a special hypoxic and acidic microenvironment for solid tumors, which in turn promotes the cancer cells to respond to cancer cells. Hypoxia produces an adaptive response. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that plays a regulatory role in a series of responses triggered by changes in intracellular oxygen content. It is an important factor for the survival of cancer cells under ischemic conditions. Immunohistochemical stu...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C43/23C07C49/84C07C41/26C07D317/54A61K31/09A61K31/12A61K31/36A61P35/00
CPCA61K31/12A61K31/36A61P35/00C07C43/23C07C49/84C07C2601/08C07D317/54
Inventor 谢平陈晓光焦晓臻刘晓宇李燕张翼郎立伟王丽萍李人则
Owner INST OF MATERIA MEDICA CHINESE ACAD OF MEDICAL SCI
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