Small molecular compound cyy-260 and application thereof in preparation of antitumor drugs

A cyy-260, small molecule compound technology, applied in the field of biomedicine, can solve problems such as inability to choose surgical resection

Active Publication Date: 2020-07-17
WENZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At diagnosis, more than 60% of lung cancer patients have locally advanced or metastatic disease (stage III or IV), at which time surgical resection may not be an option

Method used

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  • Small molecular compound cyy-260 and application thereof in preparation of antitumor drugs
  • Small molecular compound cyy-260 and application thereof in preparation of antitumor drugs
  • Small molecular compound cyy-260 and application thereof in preparation of antitumor drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] (1) Dissolve 2,4-dichloro-5-methylpyrimidine (323.96mg, 2.0mmol) and N,N-diisopropylethylamine (DIPEA) (516.96mg, 4mmol) in DMF (4mL) and cooled to 0 °C. To the mixture was added dropwise 6-aminoindazole (266.3 mg, 2 mmol) dissolved in DMF (2 mL). The reaction mixture was stirred at 0 °C for about 1 hour. Next, the ice bath was removed, the reaction mixture was stirred at room temperature, and the reaction was monitored by TLC, the resulting mixture was extracted with EtOAc (3×25 mL), washed with saturated brine, washed over anhydrous Na 2 SO 4 After drying and concentration, the intermediate product was obtained by silica gel column chromatography. The characterization data are as follows:

[0018] N-(2-chloro-5-methylpyrimidin-4-yl)-1H-indazol-6-amine

[0019] Using dichloromethane:methanol=16:1 as the eluent, a yellow solid (163.5 mg, 21.0% yield) was obtained. 1 HNMR(400MHz,DMSO)δ13.06(s,1H),8.97(s,1H),8.10(s,1H),8.03(s,2H),7.74(d,J=8.0Hz,1H),7.35( d, J=6.8Hz...

Embodiment 2

[0026] Example 2 Inhibition of lung cancer cell proliferation and clone formation test

[0027] We analyzed the effect of cyy-260 on the proliferation of lung cancer cells by MTT assay and cloning assay. Select three human lung cancer cell lines PC-9, A549, and H1975, collect the logarithmic phase cells, spread the cells in a 96-well plate at a rate of 3000 / well, and add different cyy-260 after the cells adhere to the monolayer to cover the bottom of the well Concentrations (D, 0.01, 0.05, 0.1, 0.5, 1, 2.5, 5, 10, 20 μM), 25 μl / well MTT solution (5 mg / ml) was added after 48 hours of drug action, and the incubation was continued for 4 hours in the incubator to terminate the culture. After discarding the supernatant, add 150ul DMSO / well to dissolve the crystals. The absorbance value of each well was measured in a multifunctional microplate reader OD490nm, and the half-inhibition concentration (IC50 value) was calculated with GraphPad Prism. Experimental results such as figure...

Embodiment 3

[0029] Example 3 Inhibition of Lung Cancer Cell Migration Test

[0030] We used transwell assay to evaluate the effect of cyy-260 on cell migration and invasion. Lung cancer cells PC-9 and H1975 were cultured to the logarithmic growth phase, and 600-800 μl of medium containing 10% serum was added to the lower chamber (i.e., the bottom of the 24-well plate), and 100-200 μl of cell suspension (serum-free) was added to the upper chamber. Cell number 3×10 4 -4×10 4 / well, add medicine every other day, continue to culture in the incubator for 24 hours, terminate the culture, discard the culture medium, fix with 4% paraformaldehyde and stain with crystal violet solution, take pictures and record under the microscope. The result is as image 3 shown. The results showed that cyy-260 could significantly and concentration-dependently inhibit the migration and invasion of lung cancer cells.

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Abstract

The invention discloses a small molecule compound cyy-260 and application thereof in preparation of antitumor drugs; the small molecule compound is a JAKs inhibitor, the structure of the small molecule compound is shown as a formula (I), and the small molecule compound has an inhibition effect in occurrence and development of non-small cell lung cancer. Experiments prove that cyy-260 can inhibit lung cancer cell proliferation, clone formation and migration in a concentration-dependent manner and induce apoptosis. The anti-tumor biological activity is achieved at lower concentration.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to a small molecular compound cyy-260 and its application in the preparation of antitumor drugs. Background technique [0002] Lung cancer is a heterogeneous group of tumors consisting of more than 50 histomorphological subtypes. Over the past few decades, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) have been the most commonly used diagnostic terms for lung cancer, mainly due to limited treatment options and often no further differentiation of morphological subtypes is required. [0003] NSCLC accounts for about 80% of all lung cancers, among which adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the main histological subtypes of NSCLC. Clinically, only a small proportion of early-diagnosed (stage I or II) NSCLC patients can be surgically resected. At diagnosis, more than 60% of lung cancer patients have locally advanced or metastatic dise...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D403/12A61P35/00A61P35/04
CPCC07D403/12A61P35/00A61P35/04
Inventor 刘志国赵承光黄晓颖王良兴杨乐和赵海洋庄严胡万乐戴璇璇周斌李继法
Owner WENZHOU MEDICAL UNIV
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