Compound BA-X having antitumor effect, preparation method and applications thereof

A technology of anti-tumor effects and compounds, applied in anti-tumor drugs, steroids, organic chemistry, etc., can solve the problems of lack of selectivity and side effects of drugs

Inactive Publication Date: 2018-08-28
雷鹏程
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] Tumor is still one of the major diseases that threaten human life and health. There is no effective method at present. Chemotherapy is still the main means of clinical treatment of malignant tumors. However, this type of drug lacks selectivity and kills cancer cells as well as Normal cells, so this type of drug can cause serious side effects, such as: nephrotoxicity, hepatotoxicity, neurotoxicity, etc.

Method used

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  • Compound BA-X having antitumor effect, preparation method and applications thereof
  • Compound BA-X having antitumor effect, preparation method and applications thereof
  • Compound BA-X having antitumor effect, preparation method and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0100] Example 1 Preparation of intermediate compound 1 (2-chloromethyl-3,5,6-trimethylpyrazine)

[0101] Take Ligustrazine 2.176g (16mmol) and dissolve it in 20ml glacial acetic acid, add 1.8ml (16mmol) 30% hydrogen peroxide and react at 90°C for 4h, then add 1.8ml (16mmol) 30% hydrogen peroxide to continue the reaction for 2h, and monitor the reaction by TLC Completely, add an appropriate amount of sodium sulfite to neutralize excess hydrogen peroxide, filter the reaction solution, cool the filtrate to room temperature, adjust the pH to 10 with 50% sodium hydroxide, extract with dichloromethane, collect the organic layer, and dehydrate with saturated saline. Dry over sodium sulfate, and recover the solvent under reduced pressure to obtain the crude white ligustrazine nitrogen oxide compound (2). Add 1.51ml (16mmol) of acetic anhydride to the crude product, heat to reflux at 105°C for 2.5h, monitor by TLC until the reaction is complete, then evaporate to dryness under reduced...

Embodiment 3

[0102] The preparation of embodiment 3 BH-01

[0103] Weigh 2.28g (5mmol) betulinic acid, 0.69g (5mmol) anhydrous potassium carbonate in a 50ml reaction bottle, add 25mlDMF, mix for half an hour, add 1.02g (6mmol) ligustrazine chloride, under nitrogen protection, at room temperature Under reaction for 12h, TLC detects that the reaction is complete, and a certain amount of water is added to terminate the reaction, followed by extraction with dichloromethane, and the organic layer is collected, and an appropriate amount of anhydrous sodium sulfate is used to remove water, evaporated to dryness under reduced pressure, and separated on a silica gel column [V (petroleum ether ): V (acetone) = 10: 1] to obtain 2.66 g of white solid, yield 95%. mp: 184.6-185.4°C, [α] D =+16(c 0.50, MeOH); 1 H-NMR (CDCl 3 )(ppm): 0.78, 0.80, 0.82, 0.96, 0.98, 1.67(s, 3H, 30-CH 3 of BA), 2.51(s, 3H, -CH 3 ), 2.53(s, 3H, -CH 3 ), 2.57(s, 3H, -CH 3 ), 3.02(m, 1H), 3.19(m, 1H), 4.61, 4.74(each, brs...

Embodiment 4

[0104] Example 4 Preparation of Compound BH-02

[0105] Sequentially weigh 200.00mg (0.338mmol) TBA, 77.04mg (0.44mmol) Boc-L-glycine, 97.20mg (0.50mmol) EDCI and 4.12mg (0.038mmol) DMAP into a reaction bottle containing 5ml of anhydrous DCM , stirred overnight at room temperature, when TLC detected that TBA was basically consumed, the reaction solution was diluted with 20ml of dichloromethane and washed with appropriate amount of water and saturated NaCl solution successively, dehydrated with anhydrous sodium sulfate, concentrated under reduced pressure and then separated on a silica gel column [V(2 Chloromethane): V (methanol) = 40: 1] to obtain a white solid; place the white solid in an ethyl acetate solution containing 3M HCl under ice bath and stir for 1 h, concentrate under reduced pressure to remove most of the HCl gas, and then add an appropriate amount of saturated NaHCO 3 Adjust the pH of the aqueous solution to about 8-9, extract with dichloromethane, dehydrate the...

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PUM

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Abstract

The present invention provides a class of compounds having a structure represented by a general formula 1, and a preparation method thereof, and applications in preparation of antitumor drugs. According to the present invention, the compound can significantly inhibit the growth of tumor cell lines (HepG-2, HT-29, Hela, BGC-823 and A549) while has low toxicity on Madin-Darby canine kidney (MDCK) cells, wherein the compound BH-26 has good anti-proliferative activity against colonic carcinoma cell line HT-29, human cervical cancer cell line Hela and human gastric cancer cell line BGC823 comparedto the positive drug cisplatin, and has significantly low cytotoxicity to normal Madin-Darby canine kidney (MDCK) cells compared to the positive drug cisplatin. The formula 1 is defined in the specification.

Description

technical field [0001] The invention relates to a compound and its preparation method and application, specifically a compound with anti-tumor activity and its preparation method and application, belonging to the field of medicinal chemistry. Background technique [0002] Tumor is still one of the major diseases that threaten human life and health. There is no effective method at present. Chemotherapy is still the main method for clinical treatment of malignant tumors. However, this type of drug lacks selectivity and kills cancer cells while killing Normal cells, so this type of drug will cause serious side effects, such as: nephrotoxicity, liver toxicity, neurotoxicity and so on. Therefore, it is of great significance to find anticancer drugs with high efficiency, low toxicity and strong selectivity. [0003] In the early stage, the research group used the principle of compatibility of traditional Chinese medicine and the combination principle of medicinal chemistry, suppl...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J63/00A61K31/675A61P35/00
CPCC07J63/008
Inventor 徐冰王鹏龙雷鹏程
Owner 雷鹏程
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