Quadrivalent-platinum glycosyl complex for treating tumors and preparation method thereof

A technology for tumor treatment and tetravalent platinum, which is applied in the preparation of sugar derivatives, medical preparations containing active ingredients, sugar derivatives, etc., can solve the problems of increased toxicity and side effects, inability to take oral medication, and cross-drug resistance, etc., to achieve Improve the water partition coefficient of ester, increase the maximum tolerated dose, and improve the effect of bioavailability

Inactive Publication Date: 2016-07-13
NANKAI UNIV
View PDF8 Cites 17 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, the biggest disadvantages of divalent platinum-based antineoplastic drugs are strong toxic and side effects, low in vivo availability, poor stability, and short half-life. Disadvantages of oral medication
Due to the poor water solubility of these drugs, it brings great difficulties to clinical drug use. After intravenous injection of 100mM cisplatin into the body, less than 1% of them fin

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Quadrivalent-platinum glycosyl complex for treating tumors and preparation method thereof
  • Quadrivalent-platinum glycosyl complex for treating tumors and preparation method thereof
  • Quadrivalent-platinum glycosyl complex for treating tumors and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Embodiment 1: the synthesis of tetravalent cisplatin carboxylic acid

[0061]

[0062] C2HRMS:Calcd.forCl 2 h 8 N 2 o 2 Pt(M + ):332.96,found:332.9827.

[0063] C3HRMS:Calcd.forC 4 h 12 Cl 2 N 2 o 5 Pt(M + ):432.98,found:432.9847.

Embodiment 2

[0064] Example 2: Synthesis of Glycosylated Tetravalent Platinum Final Product A1

[0065]

[0066] The preparation method is as follows: C1 (divalent platinum compound cisplatin) is oxidized with hydrogen peroxide at 60-70°C and reacted for 4 hours to prepare C2 tetravalent cisplatin compound; C2 (1equiv) and succinic anhydride ( 4equiv) was dissolved in DMF, reacted overnight at 70°C under nitrogen protection, and then the oil pump was drained. After adding dichloromethane to precipitate a solid, C4 could be prepared by washing with chloroform, ether, etc.; the DMF solution of C4 was mixed with 2-(7 -Azobenzotriazole)-N,N,N',N'-Tetramethyluronium hexafluorophosphate DMF solution was mixed and stirred for 10 minutes, then added full acetylated glucosamine and N,N-di The DMF mixture of isopropylethylamine was reacted at room temperature in the dark for 24 hours to obtain A1.

[0067] A1: 1 HNMR (400MHz, CDCl 3 )δ6.41(d,J=146.8Hz,4H),5.47–4.79(m,14H),4.64–4.08(m,5H),4.02–...

Embodiment 3

[0068] Example 3: Synthesis of Glycosylated Tetravalent Platinum Final Product A2

[0069]

[0070] The preparation method is as follows: C1 (divalent platinum compound cisplatin) is oxidized with hydrogen peroxide at 60-70°C and reacted for 8 hours to prepare C2 tetravalent cisplatin compound; C2 (1equiv) and succinic anhydride ( 4equiv) was dissolved in DMF, reacted overnight at 70°C under nitrogen protection, and then the oil pump was drained. After adding dichloromethane to precipitate a solid, C4 could be prepared by washing with chloroform, ether, etc.; the DMF solution of C4 was mixed with 2-(7 -Azobenzotriazole)-N,N,N',N'-Tetramethyluronium hexafluorophosphate DMF solution was mixed and stirred for 20 minutes, then added full acetylated rhamnosamine and N,N - DMF mixed solution of diisopropylethylamine, A2 was obtained after reaction at room temperature in the dark for 48 hours.

[0071] A2: 1 HNMR (400MHz, CDCl 3 )δ5.28(s,6H),5.22–4.89(m,5H),4.72(s,1H),3.78(d,J=...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention provides a quadrivalent-platinum glycosyl complex for treating tumors and a preparation method thereof. The synthesized compound has good anti-tumor activity better than that of cisplatin and oxaliplatin, and has better stability than that of bivalent platinums such as cisplatin, carboplatin and oxaliplatin. In addition, since the quadrivalent platinum with galactosylated modification has better targeting for tumor cells, the high selectivity to the tumor cells is improved. Furthermore, the compound provided by the invention has the advantages that the problems of poor solubility and more troublesome clinical compatibility of the original bivalent-platinum anti-tumor medicine are solved, and both fat solubility and water solubility are better. The quadrivalent-platinum glycosyl derivative not only can improve the in-vivo availability and enhance the curative effect, but also can reduce the toxic and side effects of the original bivalent-platinum medicine on the kidney and the like.

Description

technical field [0001] The invention relates to a platinum complex, in particular to a glycosyl-containing tetravalent platinum complex for tumor treatment and a preparation method of the complex. Background technique [0002] For a long time, tumors have been medically difficult to cure diseases. In the past, while drug treatment killed tumor cells, it also produced toxicity to normal cells, which caused various complications caused by drug treatment. Therefore, for tumor cells Targeted therapy has always been the focus of research. Only by selectively killing tumor cells can this major problem that threatens human health be solved. [0003] Platinum metal drugs are one of the representative drugs for anti-tumor treatment. In 1967, cisplatin was found to have anti-tumor activity. After that, it also became an anti-tumor drug with a long history and long application time. With the second generation of carboplatin and the first The third generation of oxaliplatin is graduall...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07H23/00C07H1/00A61K31/7135A61P35/00
CPCC07H1/00C07H23/00
Inventor 王欣王鹏马静
Owner NANKAI UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap