Tetravalent platinum complex containing BET inhibitor and application

An inhibitor, tetravalent platinum technology, applied in the field of medicine, can solve problems such as unclear mechanism, and achieve the effect of solving drug resistance, excellent in vitro anti-tumor activity, and excellent synergistic anti-tumor effect

Pending Publication Date: 2021-09-03
AIR FORCE MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the existing research results show that BET inhibitors are only effective on some cell lines in various tumors, and the mechanism is still unclear

Method used

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  • Tetravalent platinum complex containing BET inhibitor and application
  • Tetravalent platinum complex containing BET inhibitor and application
  • Tetravalent platinum complex containing BET inhibitor and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Synthesis of compound 1:

[0038]

[0039] Take 1.0 g of cisplatin, compound II, and add 25 mL of 30% hydrogen peroxide, react at 60° C. for 2 h, filter with suction, and leave the filtrate to obtain 0.95 g of oxoplatin, compound III, as a yellow needle-like solid, with a yield of 85%.

[0040]

[0041] Compound IV (purchased from Jilin Zhongke Shen Technology Co., Ltd., 30mg, 0.075mmol), TBTU (31mg, 0.095mmol) and triethylamine (9.5mg, 0.095mmol) were sequentially added to 2mL of dry DMF, stirred at room temperature for 10min , added compound III (25mg, 0.075mmol), and stirred at room temperature for 12h under nitrogen protection. After the reaction, the solvent was evaporated to dryness, and the residue was purified by silica gel column chromatography (DCM:MeOH=20:1) to obtain compound 1 as a white solid (38 mg, yield 70%).

Embodiment 2

[0043] Synthesis of Compound 2

[0044]

[0045] Compound 1 (30mg, 0.042mmol) and compound IV (17mg, 0.043mmol) were added to DMF (2mL), HBTU (19mg, 0.05mmol) and DIPEA (6.5mg, 0.05mmol) were added, and the reaction was stirred at room temperature for 12h After the reaction, the solvent was evaporated to dryness, and the residue was purified by silica gel column chromatography to obtain light yellow solid compound 2 (22 mg, yield 48%).

Embodiment 3

[0047] Synthesis of Compound 3

[0048]

[0049] Compound 1 (30mg, 0.042mmol) and acetic anhydride (5.1mg, 0.050mmol) were dissolved in DMF (2mL) for reaction. After 12 hours of reaction, the solvent was evaporated to dryness, and the residue was purified by silica gel column chromatography to obtain a white solid compound 3 (22 mg, yield 69%).

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PUM

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Abstract

The invention discloses a tetravalent platinum complex containing a BET inhibitor. The structure of the tetravalent platinum complex is as shown in a general formula I, wherein substituent groups are defined in the specification. The advantages of the tetravalent platinum complex are utilized, and the synergistic anti-tumor effect of the BET inhibitor and cis-platinum is exerted. The tetravalent platinum complex containing the BET inhibitor shows broad-spectrum and excellent in-vitro anti-tumor activity, the activity of the tetravalent platinum complex is obviously superior to that of cis-platinum, the BET inhibitor and the mixture of the cis-platinum and the BET inhibitor according to the ratio of 1: 1, and the tetravalent platinum complex has huge potential of being developed into a novel broad-spectrum anti-tumor drug.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a tetravalent platinum complex containing a BET inhibitor and its application in the preparation of antitumor drugs. Background technique [0002] Platinum antineoplastic drugs are widely used clinically in the treatment of malignant tumors. At present, the US FDA has approved three platinum drugs for marketing, including cisplatin, carboplatin and oxaliplatin. Cisplatin can be clinically effective against various solid tumors such as ovarian cancer, prostate cancer, testicular cancer, lung cancer, nasopharyngeal cancer, esophageal cancer, malignant lymphoma, head and neck squamous cell carcinoma, thyroid cancer and osteosarcoma. Carboplatin is the second-generation platinum drug. It is a broad-spectrum antineoplastic drug and has no cross-resistance with other anti-tumor drugs. It has cross-resistance with cisplatin. It is mainly used for small cell lung cancer, ov...

Claims

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Application Information

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IPC IPC(8): C07F15/00A61P35/00
CPCC07F15/0093A61P35/00Y02A50/30
Inventor 王胜正刘伟王溥贺优优姜茹周翼鹏
Owner AIR FORCE MEDICAL UNIV
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