A kind of platinum (ii) complex with chiral bicyclic diamine as carrier ligand and its preparation method and application

A complex and chiral technology, applied in platinum group organic compounds, platinum organic compounds, compounds containing elements of group 8/9/10/18 of the periodic table, etc., can solve problems such as treatment failure of cisplatin drugs , to achieve the effect of overcoming cisplatin resistance

Active Publication Date: 2017-09-26
SOUTHEAST UNIV
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, according to the unique pharmacological properties of cisplatin, it not only produces many side effects, such as nephrotoxicity, bone marrow suppression, nausea and vomiting, and neurotoxicity, but also interacts with sulfur-containing biomolecules, resulting in serious drug resistance, leading to the occurrence of cisplatin drugs. treatment failure

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
  • A kind of platinum (ii) complex with chiral bicyclic diamine as carrier ligand and its preparation method and application
  • A kind of platinum (ii) complex with chiral bicyclic diamine as carrier ligand and its preparation method and application
  • A kind of platinum (ii) complex with chiral bicyclic diamine as carrier ligand and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Example 1: Preparation of Ligands LR and LS.

[0037] (1) Synthesis of bicyclo[2,2,2]octane-2-alkene-7,8-trans diacid chloride

[0038] Add 4.1g (50mmol) of 1,3-cyclohexadiene into a 50mL single-necked round-bottomed flask, and slowly add 8.8g (55mmol) of fumaryl chloride dropwise at 0°C. After 12 hours of reaction, the target product bicyclo[2,2,2]octane-2-alkene-7,8-trans-diacid chloride was obtained.

[0039] (2) Synthesis of bicyclo[2,2,2]octane-2-alkene-7,8-trans diamine

[0040] 13.0g (200mmol) NaN 3and 50mL of water into a 250mL single-necked round bottom flask. Slowly add 100 mL of toluene solution of bicyclo[2,2,2]octane-2-alkene-7,8-trans-diacid chloride, the step product, into the reaction liquid at 0°C, and stir the reaction at this temperature for 3 h . After the reaction was completed, the reaction liquid was extracted with toluene (3×150 mL), and the organic phase was collected and dried over anhydrous sodium sulfate. Add the dried toluene solution ...

Embodiment 2

[0048] Example 2: Synthesis of complex 1a.

[0049] Dissolve 2.50g (6.00mmol) potassium tetrachloroplatinate and 0.84g (6.00mmol) LR in 50mL deionized water, stir and react at 30°C for 12 hours in the dark, a bright yellow precipitate is formed, filter it, wash it repeatedly with water, and dry it brightly Yellow solid powder 2.43g, yield 89%. Elem anal. Calcd for C 8 h 16 Cl 2 N 2 Pt: C, 23.66; H, 3.98; N, 6.90. Found: C, 23.41; H, 4.25; N, 7.28. IR (KBr, cm -1 ): 3194, 2939, 2916, 2869, 477, 411; 1 H NMR (300MHz, d 6 -DMSO): δ1.19-1.77 (m, 8H, CH 2 of LR), 1.80-1.91 (m, 2H, CH of LR), 2.53(d, 2H, J=5.2Hz, 2×NH 2 CH ), 5.80-6.51 (m, 4H, 2×CH NH 2 ); 13 C NMR(d 6 -DMSO / TMS, ppm): δ19.15, 19.40, 25.99, 26.03, 31.24, 63.10, 64.07.

Embodiment 3

[0050] Example 3: Synthesis of Complex 2a.

[0051] Suspend 0.41g (1.00mmol) of 1a in 120mL of deionized water, stir, add 0.30g (1.00mmol) of silver oxalate, react at 38°C in the dark for 24h, stop the reaction, and diatomaceous earth-assisted filtration to obtain a clear solution. The filtrate was concentrated to 10 mL, a large amount of solids precipitated out, refrigerated at 4°C, filtered, and dried in vacuo to obtain 0.30 g of 2a white solid with a yield of 71%. [α] D 30 =140.0° (c=0.20, DMF:H 2 O=1:1).Elem anal.Calcd for C 10 h 16 N 2 o 4 Pt: C, 28.37; H, 3.81; N, 6.62. Found: C, 28.63; H, 3.57; N, 6.83. IR (KBr, cm -1 ): 3274 (NH), 3131, 2943, 1704, 1660, 1589, 1372, 1153, 807; 1 H NMR (300MHz, d 6 -DMSO): δ1.17-1.65 (m, 8H, CH 2 of LR), 1.69-1.72 (m, 2H, CH of LR), 2.26(d, 2H, J=9.0Hz, 2×NH 2 CH ), 5.31-5.69 (m, 4H, 2×CH NH 2 ); 13 C NMR(d 6 -DMSO / TMS, ppm): δ19.22, 25.99, 31.17, 64.46, 165.87; ESI-MS: m / z [M+Na] + =446(100%).

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 platinum (II) complex using chiral bicyclodiamine as a carrier ligand. According to the platinum (II) complex, bicyclo[2,2,2]octane-7R,8R-diamine (LR for short) or bicycle[2,2,2]octane-7S,8S-diamine (LS for short) with the optical activity is used as the carrier ligand, and any one of chloride ions, oxalate, malonate, 1,1-cyclosuccinate, 3-hydroxy-1,1-cyclosuccinate and 3-carbonyl-1,1-cyclosuccinate as a leaving group. The invention further provides application of the platinum complex in preparation of an anti-tumor drug. The in-vitro antitumor activity of the complex is equal to cis-platinum and oxaliplatin; the representative complex has the characteristic of certainly overcoming the drug resistance of cis-platinum; the platinum (II) complex is a potential antitumor platinum drug.

Description

technical field [0001] The invention relates to a novel platinum complex for treating cancer and a preparation method thereof, in particular to an anti-tumor compound using chiral bicyclo[2,2,2]octane-7,8-diamine as a carrier ligand Platinum(II) complexes and methods for their preparation and use. Background technique [0002] Cancer is the second leading cause of human death after cardiovascular and cerebrovascular diseases. Current treatment methods include: chemotherapy, radiotherapy and surgical treatment, wherein chemotherapy is one of the main methods for treating cancer. As a cell cycle non-specific anti-tumor drug, small-molecule platinum-based drugs have the characteristics of strong anti-cancer effect, high anti-cancer activity, and synergistic effects with a variety of anti-tumor drugs. main option for . At present, cisplatin, carboplatin and oxaliplatin have been used clinically all over the world and have played an important role in cancer treatment. [0003...

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
Patent Type & Authority Patents(China)
IPC IPC(8): C07F15/00A61P35/00
CPCC07F15/0093
Inventor 苟少华刘峰帆
Owner SOUTHEAST 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