Zidovudine spliced 4-aniline quinazoline compound as well as preparation method and application thereof

A technology of quinazoline and zidovudine, applied in the field of chemistry, can solve the problems of drug resistance, limited selection, and inability to effectively kill cancer cells.

Pending Publication Date: 2022-05-06
遵义医药高等专科学校
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, these 4-anilinequinazoline compounds only have an inhibitory effect on tumors and cannot effectively kill cancer cells. Only about 60% of patients with non-small cell lung cancer

Method used

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  • Zidovudine spliced 4-aniline quinazoline compound as well as preparation method and application thereof
  • Zidovudine spliced 4-aniline quinazoline compound as well as preparation method and application thereof
  • Zidovudine spliced 4-aniline quinazoline compound as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] The chemical synthesis of zidovudine splicing 4-aniline quinazoline compounds with general formula (I), the preparation methods are shown in Table 1, the preparation methods of compounds IVa~IVd are exactly the same, but it should be emphasized that the compounds of the present invention are not limited to Contents shown in Table 1.

[0035] Table 1 has a chemical synthesis of formula (I) zidovudine splicing 4-aniline quinazoline compounds

[0036]

[0037] Take the quinazoline intermediate (Ia, 0.10g, 0.32mmol) in a 25mL reaction tube, add 10mL of N,N-dimethylformamide, stir to dissolve it completely, then add anhydrous potassium carbonate (0.13g , 0.95mmol, 3.0eq) and stirred for 10min, slowly added propargyl bromide (45.0mg, 0.38mmol, 1.2eq.), stirred at room temperature, monitored by thin-layer chromatography (TLC), the reaction was complete in about 15 hours, and the reaction solution was added Dilute with 50mL of ethyl acetate, then add 50mL of water for extra...

Embodiment 2

[0043] The chemical synthesis of zidovudine splicing 4-aniline quinazoline compounds with general formula (II), the preparation method is shown in Table 2, the preparation methods of compounds VIIa~VIIb are exactly the same, but it should be emphasized that the compounds of the present invention are not limited to Table 2 shows the content.

[0044] Table 2 has a chemical synthesis of formula (II) zidovudine splicing 4-aniline quinazoline compounds

[0045]

[0046] Take the quinazoline intermediate (Va, 0.10g, 0.31mmol) into a 25mL reaction tube, add 10mL of N,N-dimethylformamide, stir to dissolve it completely, then add anhydrous potassium carbonate (0.13g , 0.95mmol, 3.0eq) and stirred for 10min, slowly added propargyl bromide (45.0mg, 0.38mmol, 1.2eq.), stirred at room temperature, monitored by thin-layer chromatography (TLC), the reaction was complete in about 15 hours, and the reaction solution was added Dilute with 50mL of ethyl acetate, then add 50mL of water for e...

Embodiment 3

[0050] MTT method was used to test the effect of compounds IVa~IVd, VIIa~VIIb on human non-small cell lung cancer cell line (A549), human breast cancer cell line (MCF-7), human cervical cancer cell line (Hela), human liver cancer cell line (HepG2 ), the in vitro anti-tumor activity of human lung adenocarcinoma cisplatin-resistant strain (A549 / DDP), and the description of the test method with A549 cells. But it should be emphasized that the compound of the present invention is not limited to human non-small cell lung cancer cell line (A549), human breast cancer cell line (MCF-7), human cervical cancer cell line (Hela), human liver cancer cell line (HepG2), Cytotoxicity expressed by a cisplatin-resistant strain of human lung adenocarcinoma (A549 / DDP).

[0051] (a) Cell recovery: Take out the A549 cells from the liquid nitrogen, quickly put them into a 37°C water bath, shake the cryopreservation tube gently to dissolve the cryopreservation solution; after dissolving, transfer the...

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Abstract

The invention discloses a zidovudine spliced 4-aniline quinazoline compound as well as a preparation method and application of the zidovudine spliced 4-aniline quinazoline compound. The compound simultaneously contains zidovudine and 4-aniline quinazoline skeleton structures, has potential biological activity, provides a compound source for biological activity screening, has important application value for drug screening and pharmaceutical industry, and has a good application prospect through in-vitro anti-tumor activity screening. It is found that the compounds have a remarkable inhibition effect on a human non-small cell lung cancer cell line (A549), a human breast cancer cell line (MCF-7), a human cervical cancer cell line (Hela), a human liver cancer cell line (HepG2) and a human lung adenocarcinoma cis-platinum-resistant strain (A549/DDP), and the anti-tumor effect strength of part of the compounds is 10 times or above that of positive control erlotinib. The inhibition of EGFR enzyme activity shows that the compound can synergistically play an anti-tumor role from a plurality of signal channels, and has the potential to be developed into a new anti-tumor drug.

Description

technical field [0001] The invention relates to the field of chemical technology, in particular to a zidovudine-spliced ​​4-aniline quinazoline compound and its application in antitumor-related drugs. Background technique [0002] Zidovudine, also known as azidethymidine, is usually used alone or in combination with other drugs to treat human immunodeficiency virus (HIV) infection. Studies in recent years have shown that zidovudine can exert anti-tumor and radiosensitizing effects by inhibiting telomerase activity, and its anti-tumor related research has involved breast cancer, cervical cancer, ovarian cancer, vaginal cancer, T lymphoma, primary Kitt lymphoma, glioma, liver cancer, gastric cancer, bladder cancer, parathyroid cancer, colon cancer, lung cancer, prostate cancer, Kaposi's sarcoma, head and neck cancer, laryngeal squamous cell carcinoma, oral cancer, leukemia and other tumors Treatment, and the curative effect research on malignant tumors such as parathyroid can...

Claims

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Application Information

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IPC IPC(8): C07H19/073C07H1/00C07H1/06A61P35/00
CPCC07H19/073C07H1/00C07H1/06A61P35/00Y02P20/55
Inventor 梁光平杨俊朱绪秀文露滴
Owner 遵义医药高等专科学校
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