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A targeted compound that treats brain glue female celloma

A technology of compound and composition, which is applied to the targeted drug-Nes0694 for the treatment of glioblastoma. In the field of glioblastoma, it can solve the problem of lack of targeted chemotherapy drugs for glioblastoma, and achieve the effect of inhibiting growth and having tumor specificity

Active Publication Date: 2018-05-04
苏州麦迪耐斯医药科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There is still a lack of targeted chemotherapy drugs for the treatment of glioblastoma

Method used

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  • A targeted compound that treats brain glue female celloma
  • A targeted compound that treats brain glue female celloma
  • A targeted compound that treats brain glue female celloma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1 Formula (VI) compound-Nes0694: (5-(E)-2-(7-chloroquinolin-2-yl)vinyl)-N-(2-(diethylamino)ethyl)-2, Synthesis of 4-Dimethyl-1H-pyrrole-3-carboxamide)

[0049] Step 1.1 Synthesis of N-(2-(diethylamino)ethyl)-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide (compound 2)

[0050]

[0051] Compound 1 (12g, 71.8mmol), EDCI (20.7g, 107.8mmol), HOBt (14.6g, 108mmol), triethylamine (20mL), N,N-diethylethylenediamine (12mL) and DMF (60mL ), the reaction mixture was stirred overnight at room temperature, extracted with dichloromethane (500 mL), washed twice with saturated sodium carbonate and saturated saline solution (100 mL), respectively, dried over anhydrous sodium sulfate, concentrated, and washed with n-hexane and ethyl acetate ( 3:1) beating, suction filtration and drying to obtain 8.1 g of solid N-(2-(diethylamino)ethyl)-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide ( Compound 2), yield: 42.6%.

[0052] EI-MS MS(m / z):266.1(M + )

[0053] Step 1.2: Synthesi...

Embodiment 2

[0066] The human glioblastoma cell line was U251 cell line (purchased from ATCC, USA), and the in vitro culture medium was DMEM plus 10% fetal bovine serum. The human neural stem cell strain (NSC, Neural stem cell) used the H9 cell line (purchased from Thermo Fisher, USA), and the in vitro culture medium used DNEM / F-12 plus 10 ng / ml of EGF and FGF nutritional factors.

[0067] After U251 and NSC cells adhered to the culture dish, 10nM Neso694 or the same volume of DMSO was added to the culture medium to treat the cells for 48 hours, and then the cells were collected and fixed with 4% paraformaldehyde for 15 minutes. protein situation. The primary antibody was rabbit anti-human nestin antibody (purchased from Abcam, 105389#), and the secondary antibody was goat anti-rabbit IgG antibody carrying green fluorescence (purchased from Abcam, 15007#). Nuclei of all cells were stained with DAPI. The proportion of Nestin-positive cells after drug treatment was compared under a fluores...

Embodiment 3

[0071] 1×10 6 U251 cells were suspended in 10 μL Mg-free ++ / Ca++ in Hank's balanced salt solution, then mixed the U251 cell suspension and Matrigel (basement membrane matrix) at a ratio of 1:1, and injected 20 μL of the mixed cell solution subcutaneously into 30 Swiss Nude mice (Swiss Nude mice ). The size of the tumor was measured with a vernier caliper, and the volume of the tumor was calculated by the formula: length × width × [0.5 × (length + width)]. When the tumor volume increased to 200mm 3 Afterwards, the mice were randomly divided into 3 treatment groups:

[0072] (1) 10 mice (DMSO control group) received intraperitoneal injection of 20 μL DMSO per day;

[0073] (2) 10 mice received daily intraperitoneal injection of 10mg / kg Neso694;

[0074] (3) 10 mice received daily intraperitoneal injection of 20mg / kg Neso694.

[0075] The tumor volume was calculated by calipers measurement every two days. After three weeks, the tumor size of the control group exceeded 10% of ...

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Abstract

The invention provides a targeted compound Nes0694 for treating glioblastoma multiforme and a preparation method thereof, an application thereof in preparation of medicines for treating tumors, as well as an application in preparation of medicines for treating tumors taking nidogen as a promising target, particularly an application in preparation of medicines for treating brain glioma.

Description

technical field [0001] The invention relates to the field of biotechnology, in particular to a targeted drug for treating brain glioblastoma-Nes0694. Background technique [0002] Nestin, an intermediate filament protein, can be specifically expressed as a molecular marker on neuroepithelial stem cells; it is a characteristic marker of neural stem cells. NESTIN is widely expressed in early embryonic development and in damaged tissues. Research reports in recent years have shown that some tumor stem cells also express nestin, and nestin can be used as a marker of some tumor stem cells. Nestin is also expressed in many tumor cells, including brain glioblastoma, lung small cell carcinoma, skin basal cell carcinoma, and malignant sarcoma. At present, the role of nestin in the development of tumors is still inconclusive. [0003] Glioblastoma is a common malignant brain tumor. Although surgery combined with radiotherapy and chemotherapy, the survival of most patients is less ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D401/06A61K31/4709A61P35/00
CPCC07D401/06
Inventor 杨增杰
Owner 苏州麦迪耐斯医药科技有限公司
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