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A kind of xanthone-no donor compound and its preparation method and application in the preparation of antitumor drugs

A compound and donor technology, applied in the Xanthone-NO donor compound and its preparation, the application field in the preparation of anti-tumor drugs, to achieve excellent in vitro tumor cell proliferation inhibitory activity, high yield, and the effect of inhibiting in vitro proliferation

Active Publication Date: 2019-12-24
JINAN UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, due to the large clinical dose of DMXAA, it shows certain cardiotoxicity and causes certain anxiety and depression in patients during clinical application.

Method used

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  • A kind of xanthone-no donor compound and its preparation method and application in the preparation of antitumor drugs
  • A kind of xanthone-no donor compound and its preparation method and application in the preparation of antitumor drugs
  • A kind of xanthone-no donor compound and its preparation method and application in the preparation of antitumor drugs

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Embodiment 1: Preparation of Xan-NO-1 compound

[0046] (1) Synthesis of 6-methyl-1,3-dihydroxyxanthone: measure POCl 3 (8mL) with anhydrous ZnCl 2 (3.6g) were mixed, and the mixed powder of 4-methylsalicylic acid (0.152g, 1.0mmol) and phloroglucinol (0.151g, 1.2mmol) was added, and after reacting at 85°C for 3h, it was cooled to room temperature, and the cooled The product was poured into ice water, stirred for 1 h, allowed to stand for 1 h, filtered with suction, extracted with ethyl acetate (3×50 mL), washed the filter cake with water until neutral, and dried the filter residue by column chromatography (mobile phase: petroleum ether-ethyl acetate ester) to obtain 0.17 g of a light yellow powder solid, with a yield of 70.1%. 1 H NMR (CD 3 OD,300mHz)δ:10.85(s,1H,OH),7.96(d,J=8.1Hz,1H,H-8),7.71(d,J=8.1Hz,1H,H-5),7.34(t ,J=8.1Hz,1H,H-7),6.43(d,J=8.1Hz,1H,H-4),6.22(d,J=8.1Hz,1H,H-2); 13 C NMR (DMSO-d6, 75mHz) δ: 180.4 (C-9), 166.4 (C-3), 163.2 (C-1), 157.72 (C-4a), 155...

Embodiment 2

[0050] Embodiment 2: the preparation of Xan-NO-2 compound

[0051] (1) The preparation of 6-methyl-1,3-dihydroxyxanthone is the same as in Example 1.

[0052] (2) Synthesis of 3-O-(4-bromobutyl)-6-methyl-1-hydroxyxanthone: replace 1,3- with 1,4-dibromobutane (0.324g, 1.5mmol) Dibromopropane, other steps are the same as above. 0.376 g of white powder was obtained, with a yield of 99.6% and a purity of 99.2%.

[0053] (3) Replace 3-O-(3-bromopropyl)-6-methyl with 3-O-(4-bromobutyl)-6-methyl-1-hydroxyxanthone (0.377g, 1.0mmol) Base-1-hydroxyxanthone, other steps are the same as above. 0.198 g of white powder was obtained with a yield of 55.1%. M.p.:146-148℃; 1 H NMR (CDCl 3 ,300mHz)δ:12.90(s,1H,OH),8.08(d,J=8.4Hz,1H,H-8),7.17(m,2H,H-5,7),6.36(d,J=1.2 Hz,1H,H-4),6.29(d,J=1.2Hz,1H,H-2),4.06(t,J=5.7Hz,2H),3.50(t,J=5.7Hz,2H),2.48 (s,3H,CH 3 ),2.01-2.10(m,4H); 13 C NMR (CDCl 3 ,75mHz)δ:180.77(C-9),165.87(C-1),163.60(C-3),157.78(C-4b),156.23(C-4a),146.79(C-6),125.69(C -8), ...

Embodiment 3

[0055] Embodiment 3: the preparation of Xan-NO-3 compound

[0056] (1) The synthesis of 6-methyl-1,3-dihydroxyxanthone is the same as in Example 1.

[0057] (2) Synthesis of 3-O-(5-bromopentyl)-6-methyl-1-hydroxyxanthone: replace 1,3- with 1,5-dibromopentane (0.345g, 1.5mmol) Dibromopropane, other steps are the same as above. 0.39 g of white powder was obtained with a yield of 99.7% and a purity of 99.3%.

[0058] (3) Replace 3-O-(3-bromopropyl)-6-methyl with 3-O-(5-bromopentyl)-6-methyl-1-hydroxyxanthone (0.391g, 1.0mmol) Base-1-hydroxyxanthone, other steps are the same as above. 0.217 g of white powder was obtained, with a yield of 58.2%. M.p.: 151-153°C; 1 H NMR (CDCl 3 ,300mHz)δ:12.93(s,1H,OH),8.09-8.12(m,1H,H-8),7.14-7.20(m,2H,H-5,7),6.38(d,J=1.2Hz ,1H,H-4),6.31(d,J=1.2Hz,1H,H-2),4.05(t,J=5.7Hz,2H),3.45(t,J=5.7Hz,2H),2.50( s,3H,CH 3 ),1.94-1.99(m,2H),1.80-1.85(m,2H),1.51-1.57(m,2H); 13 C NMR (CDCl 3 ,75mHz)δ:180.72(C-9),165.82(C-1),163.55(C-3),157.73(C-4b),156....

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Abstract

The invention belongs to the technical field of antitumor drugs and discloses a Xanthone-NO donor compound and a preparation method thereof and application in preparation of an antitumor drug. The Xanthone-NO donor compound has a structure as shown in the formula I in the specification. In the formula I, R1, R2 and R3 are the same or different (are respectively H, OH, Cl, Br or F); and n= 2-8. Thepreparation method comprises the following steps: xanthones is prepared from substituted salicylic acid and phloroglucinol; then, xanthones react with 1,n-dibromosubstituted alkane to prepare 3-O-bromoalkyl xanthone; and finally bromine conversion is carried out. The compound of the invention has excellent in vitro tumor cell proliferation inhibitory activity and can conduct multi-target induction of cancer cell apoptosis. Thus, the compound can be applied in the preparation of an antitumor drug, especially drugs for multi-target therapy of cancers and drugs for therapy of tumors caused by nitric oxide anomaly.

Description

technical field [0001] The invention belongs to the technical field of antitumor drugs, and in particular relates to a Xanthone-NO donor compound, its preparation method and its application in the preparation of antitumor drugs. Background technique [0002] With the continuous increase of the world's total population, the acceleration of population aging, and the aggravation of environmental pollution, cancer has become one of the high-incidence diseases that threaten human health today. In many developed countries, the incidence of tumors has been increasing, and it has become the number one fatal disease. In developing countries, the number of people suffering from tumors is also increasing, and researchers are constantly working hard to seek, research, and develop new Cancer treatment drugs. Although some therapeutic methods have a certain therapeutic effect, they usually bring severe systemic toxicity, accelerate cancer metastasis and recurrence, and there is still a c...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D311/86A61P35/00
Inventor 陈河如刘杰王怀玲刘志军张磊
Owner JINAN UNIVERSITY