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A kind of gambogic acid amide derivative and its preparation method and application

A technology for gambogic acid amides and derivatives, which is applied in the field of gambogic acid amide derivatives and their preparation, can solve problems such as adverse reactions and large immunosuppression, and achieves good targeting, broad-spectrum anti-tumor activity, chemical structure stable effect

Inactive Publication Date: 2016-05-04
DONGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, most antineoplastic drugs are synthetic drugs, which have the disadvantages of large adverse reactions and immunosuppression. Therefore, it has become a hot spot in medical research to find new anticancer drugs and methods, reduce adverse reactions of chemotherapy, and improve the quality of life of patients.

Method used

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  • A kind of gambogic acid amide derivative and its preparation method and application
  • A kind of gambogic acid amide derivative and its preparation method and application
  • A kind of gambogic acid amide derivative and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Synthesis of SZY-103

[0043] step:

[0044] Gambogic acid (500mg, 0.71mmol), cytarabine (156mg, 0.64mmol) were dissolved in N,N-dimethylformamide (5.0mL) at room temperature, and then DIEA (100mg, 0.78mmol) was added to the mixture ) and HOBT (105mg, 0.78mmol), after stirring for 5 minutes, TBTU (249mg, 0.78mmol) was added, the temperature was raised to 40°C, and stirred for 3 hours. Ethyl acetate (50ml) was added to the reactant to quench, then poured into saturated brine (3×10ml) to wash, dried over anhydrous sodium sulfate, and evaporated to remove ethyl acetate. Column chromatography [V (methanol): V (dichloromethane) = 1.5: 100] was eluted to obtain 357 mg of orange-yellow amorphous powder with a yield of 58.9%. 1H NMR

[0045](CDCl3,400MHz)δ:12.80(s,1H,6-OH),8.21(d,J=7.3Hz,1H,41-H),7.59(d,J=6.96Hz,1H,10-H), 6.55(d, J=10.12Hz, 1H, 4-H), 6.14(d, J=3.12, 2H, 5'-H, 6'-H), 5.73~(m, 1H, 27-H), 5.43 (d, J=10.16Hz, 1H, 3-H), 5.04~5.08(m, 1H, 32-H, 37-H), 4.50(m, 1H,...

Embodiment 2

[0047] Synthesis of SZY-110

[0048] step:

[0049] Gambogic acid (500mg, 0.71mmol), gemcitabine (169mg, 0.64mmol) were dissolved in dichloromethane (5.0ml) at room temperature, then EDCI (150mg, 0.78mmol) and HOBT (105mg, 0.78mmol) were added to the mixture , stirred for 30 minutes, then added TBTU (249 mg, 0.78 mmol), raised the temperature to 50° C., and stirred for 5 hours. Ethyl acetate (50ml) was added to the reactant to quench, then poured into saturated brine (3×10ml) to wash, dried over anhydrous sodium sulfate, and evaporated to remove ethyl acetate. Column chromatography [V (methanol): V (dichloromethane) = 1.5: 100] gave 326 mg of an orange-yellow amorphous powder with a yield of 52.6%. 1 HNMR (CDCl 3 ,400MHz)δ:12.80(s,1H,6-OH),8.18(m,1H,5”-OH),7.56(d,J=6.92Hz,1H,10-H),6.55(d,J= 10.12Hz, 1H, 4-H), 6.19(m, 1H, 1”-H), 5.81~5.85(m, 1H, 27-H), 5.40(d, J=10.16Hz, 1H, 3-H) ,5.00~5.03(m,1H,32-H,37-H),4.57(m,1H,3”-H),4.05(m,1H,4”-H),3.95(m,1H,5” -H), 3.49~3.52(m, 1H,...

Embodiment 3

[0051] In vitro anti-tumor activity test

[0052] 1. Experimental cell line:

[0053] The tumor cell lines used in this experiment are: A549 (human lung adenocarcinoma cells), HCT116 (human colon cancer cells), ZR-75-30 (human breast cancer cells) and PANC-1 (human pancreatic cancer cells) (by Cryopreservation and passage in Pharmacology Laboratory, Shanghai Institute of Pharmaceutical Industry).

[0054] 2. Sample preparation:

[0055] After dissolving in DMSO (Merck), add PBS (-) to make a 1000 μg / ml solution or a homogeneous suspension, and then dilute with DMSO-containing PBS (-). The positive control drug was gambogic acid.

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Abstract

The invention relates to garcinia acid amide derivative and preparation method thereof and purpose, and the structural formula of the derivative is shown as formula (I); The preparation method comprises the following steps: garcinia acid and nucleoside medicament or salt nucleoside of nucleoside medicament melted in an inertia solvent under room temperature; then a catalyzed condensation reagent is added for reaction for 3 to 5 hours by blending at the temperature between 40 and 60 DEG C; and garcinia acid amide derivative is obtained after washing, drying, distillation andn column chromatography. The derivative of the present invention can be used for used to prepare compositions, antineoplastic drugs, antimycotics drugs or anti-angiogenic drugs generation medicament or be used with other anticancer active components. The compound of the present invention not only displays better activity to a plurality of tumor cells, shows good targeting to tumor cells, which makes a good foundation for novel medicament exploitation.

Description

technical field [0001] The invention belongs to the field of gambogic acid derivatives and their preparation methods and applications, in particular to a gambogic acid amide derivatives and their preparation methods and applications. Background technique [0002] Malignant tumors are one of the major diseases that seriously threaten human life and quality of life. At present, most antineoplastic drugs are synthetic drugs, which have the disadvantages of large adverse reactions and immunosuppression. Therefore, finding new anticancer drugs and methods, reducing adverse reactions of chemotherapy, and improving the quality of life of patients has become a hot spot in medical research. Because of their ability to inhibit tumor growth and have less toxic and side effects, traditional Chinese medicines and herbal medicines have received widespread attention from medical workers. [0003] Gambogic acid is a compound with high anti-tumor activity and good cell selectivity extracted...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H19/09C07H19/073C07H1/00A61K31/7068A61P35/00
Inventor 邵志宇宋云龙吴孟强孙中强赵圣印邓云霞
Owner DONGHUA UNIV
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