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Bis-biguanide, preparation method thereof and application of bis-biguanide

A compound and biguanide technology, applied in the field of medicine, can solve the problems of high cost, lack, curative effect and safety of drugs, etc., to reduce hematopoietic function damage, increase blood cell level, good in vitro activity and animal treatment effect Effect

Inactive Publication Date: 2015-08-12
高尔医药科技(上海)有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But it should be noted that its estrogenic effect greatly affects its wide application
Some other compounds, such as flavonoids, TLR ligands, cytokines and growth factors, have been funded by large foreign companies for research, and some of them have entered the first phase of clinical trials, but their efficacy and safety are still inconclusive, and some drugs are extremely expensive. Expensive, widespread use questionable
In short, at present, there is a lack of relevant safe and effective drugs in China, and there is an urgent need to develop new drugs with less toxicity and better efficacy in clinical practice.

Method used

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  • Bis-biguanide, preparation method thereof and application of bis-biguanide
  • Bis-biguanide, preparation method thereof and application of bis-biguanide
  • Bis-biguanide, preparation method thereof and application of bis-biguanide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] Embodiment 1 (synthesis of SDF-gf-106)

[0062] In a 250ml round bottom bottle, add metformin 2g (12mmol), anhydrous acetone 200ml, sodium iodide 3.4g (24mmol), ice bath, stir, add dropwise bromooctane 2.31g (12mmol) and anhydrous acetone 10ml mixed solution , magnetic stirring, thin layer chromatography (TLC) tracking reaction (developing solvent: dichloromethane: methanol: triethylamine = 4.3:0.7:3dr). Reaction at room temperature for 32 hours, post-treatment.

[0063] The reaction solution was filtered, and the filtrate was evaporated to dryness to obtain 2.2 g of an oily substance. The oil was separated with 200-300 mesh silica gel, mobile phase dichloromethane:methanol gradient to obtain 0.55 g of the target product. Yield 19%. 1H NMR(600MHz,DMSO)δ6.86(s,4H),3.04(dd,J=13.4,6.5Hz,2H),2.92(s,6H),1.46(m,2H),1.26(s,10H) , 0.86 (t, J = 7.0 Hz, 3H). HRMS [M+H] 242.41.

Embodiment 2

[0064] Embodiment 2 (synthesis of SDF-gf-111)

[0065] In a 250ml round bottom bottle, add metformin 2g (12mmol), anhydrous DMF 100ml, ice bath, stir, add sodium iodide 3.4g (24mmol), then add dropwise 4-methylbenzyl bromide 2.22g / 1.68ml (12mmol ) and anhydrous MDF15ml mixed solution, magnetic stirring, thin layer chromatography (TLC) tracking reaction (developing solvent: dichloromethane: methanol: triethylamine=4.3:0.7:3dr). Almost complete reaction to metformin hydrochloride. Reaction at room temperature for 15 hours, post-treatment.

[0066] Filter and wash with a little DMF. The filtrate was evaporated to dryness, dichloromethane was added and stirred to obtain about 1.9 g of solid. The solid was recrystallized from acetonitrile to obtain 1.28 g of the target pure product. Yield 45%. 1 H NMR (600MHz, DMSO) δ7.17(d, J=7.9Hz, 2H), 7.03(d, J=7.9Hz, 2H), 5.22(s, 3H), 4.12(s, 2H), 3.34(s , 1H), 2.77(s, 6H), 2.25(s, 3H). HRMS [M+H] 234.37.

Embodiment 3

[0067] Embodiment 3 (synthesis of SDF-gf-117)

[0068] In a 100ml round bottom bottle, add metformin hydrochloride 2g (12mmol), dichloromethane 25ml, ice bath, add 25% sodium hydroxide 10ml, stir, add 4-isopropylbenzyl bromide 2.56g / 2.00ml ( 12mmol), potassium iodide 3 pellets, tetrabutylammonium bromide 0.1g, magnetic stirring, thin layer chromatography (TLC) tracking reaction (developing solvent: dichloromethane: methanol: triethylamine = 4.3:0.7:3dr). A little colorless solid was seen in the reaction flask. Almost complete reaction to metformin hydrochloride. A total of 35 hours at room temperature, post-processing.

[0069] After filtration, 0.1 g of solid was obtained. The filtrate was transferred to a separatory funnel, and the organic layer and the water layer were separated. The water layer was extracted three times with 10 ml of dichloromethane, the organic layers were combined, and the dichloromethane was evaporated to obtain 2.6 g of an oily substance. The solid...

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PUM

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Abstract

The invention relates to bis-biguanide, a preparation method thereof and an application of the bis-biguanide. The bis-biguanide has the advantages that a novel anti-irradiated injury series compound is designed and synthesized, the novel compound which is high-efficiency and low-toxicity is found out and can be used for anti-irradiated injury in the field of civil use and military, by the novel compound, hematopoietic function injury caused by radiation or chemotherapy drugs is reduced, and blood cellular level is increased, or tumor auxiliary treatment is implemented; and a molecular level and animal pharmacological activity test is performed by the compound, and a result shows that the bis-biguanide has high in-vitro activity and high animal treatment effect generally.

Description

technical field [0001] The invention relates to the technical field of medicine, specifically, a class of biguanide compounds, a preparation method thereof and its preparation for reducing hematopoietic function damage caused by radiation or chemotherapy drugs, increasing blood cell levels, or adjuvant treatment of tumors, and can also be used for Anti-radiation damage applications in civil and military fields. Background technique [0002] Radiation is more harmful to organisms, it can directly act on DNA, proteins and enzymes, causing ionization and excitation to break chemical bonds, causing molecular denaturation and cell structure damage; it can also act on water molecules in the body to cause ionization and excitation, A large number of free radicals with strong oxidative properties are produced, which indirectly causes tissue cell degeneration and necrosis, resulting in metabolic disorders of the body, causing a series of diseases such as regulatory dysfunction of the...

Claims

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Application Information

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IPC IPC(8): C07C279/26C07C277/08A61K31/155A61P17/16A61P35/00A61P39/00
Inventor 苏定冯刘爱军吕加国
Owner 高尔医药科技(上海)有限公司
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