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Parthenolide derivative, and medicinal composition, preparation method and use thereof

A technology of drugs and uses, applied in drug combinations, pharmaceutical formulations, anti-tumor drugs, etc., can solve problems such as drug resistance and insensitivity of tumor stem cells

Active Publication Date: 2017-02-01
ACCENDATECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Traditional chemotherapy drugs for tumor treatment have drug resistance problems, especially cancer stem cells are less sensitive

Method used

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  • Parthenolide derivative, and medicinal composition, preparation method and use thereof
  • Parthenolide derivative, and medicinal composition, preparation method and use thereof
  • Parthenolide derivative, and medicinal composition, preparation method and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Mode( I ) in mono- and di-fluoro substituted parthenolide derivatives I-1 ， I-2 and I-4 preparation of

[0025]

[0026] compound 2 Synthesis of: parthenolide (1.0 g, 4.3 mmol), SeO 2 (324 mg, 2.4 mmol) with Na 2 SO 4 pre-dried t -BuOOH ( 70% in H 2 O, 1.48 mL, 10.8 mmol) in dichloromethane (20 mL) at room temperature for 4 days, concentrated under reduced pressure, silica gel column chromatography (petroleum ether: ethyl acetate = 1:2), and obtained 810 mg of white solid , Yield: 72%. mp 171–173 o C; [α] D 21 –33.9 o ( c 1.0, CHCl 3 ); IR (KBr) 3466, 3096, 2957, 2867, 1747, 1309, 1151, 818 cm – 1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 6.20 (d, J = 3.4 Hz, 1H), 5.63 (t, J = 8.1 Hz, 1H), 5.54 (d, J = 3.1 Hz, 1H), 4.14 (d, J = 12.7 Hz, 1H), 4.05 (d, J = 12.7 Hz, 1H), 3.84 (t, J = 9.3 Hz, 1H), 2.84 (d, J = 9.4 Hz, 1H), 2.81 (m, 1H), 2.47–2.35 (m, 3H), 2.31–2.24 (m, 1H), 2.20–2.10 (m, 2H), 1.98 (br s, 1H), 1.63 (t, J = 11.2 Hz,...

Embodiment 2

[0032] Mode( I ) in trifluoromethylated parthenolide derivatives I-3 preparation of

[0033]

[0034] compound 6 The synthesis of: under the protection of argon, the compound 5 (12.34 g, 62.93 mmol) was dissolved in dry tetrahydrofuran (125 mL), and NaHMDS (2 M in THF, 63.0 mL, 126.0 mmol) was added in an ice-water bath. After stirring for half an hour, dry tetrahydrofuran (250 mL) was added . Then the compound 4 (14.23 g, 75.53 mmol) was slowly added dropwise. Stirred under ice-water bath for 4 h, with KHSO 4 The solution (0.5 M) was quenched, and the pH of the solution was adjusted to 4, extracted, concentrated under reduced pressure, and silica gel column chromatography (petroleum ether: ethyl acetate = 20:1-8:1) to obtain the compound 6 (11.67 g, 80%). Colorless oil, IR (KBr) 3069, 2986, 2930, 2856, 1587, 1470, 1308, 1217, 1110, 704 cm – 1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 11.70 (s, 1H), 5.95 (s, 1H), 4.05 (s, 2H), 1.97 (s, 3H), 0.84 (s, 9H), 0.00 (s...

Embodiment 3

[0047] Example 3 : Pharmacological effects of parthenolide derivatives

[0048] Match various cancer cells into 2×10 5 / mL cell suspension, add to 24-well round-bottomed cell culture plate, add woody hydrocarbon lactone derivatives or their salts respectively, 5 wells for each test concentration, place at 37 ℃, 5% CO 2 After culturing under saturated humidity conditions for 18 hours, the absorbance (A) value was measured at a wavelength of 570 nm in an enzyme-linked detector by the MTT method, and the inhibitory effect of the compound of the present invention on the test cancer cells was calculated.

[0049] Table 1 Inhibitory activity of parthenolide derivatives on various cancer cells (IC 50 , μM)

[0050] [0056] cell

[0057] Compound I-1

[0058] Compound I-2

[0059] Compound I-3

[0060] Compound I-4

[0061] HL-60

[0062] 2.0

[0063] 2.0

[0064] 2.1

[0065] 6.3

[0066] HL-60 / A

[0067] 1.5

[0...

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Abstract

The invention relates to a parthenolide derivative, and a medicinal composition, a preparation method and a use thereof. The parthenolide derivative is a compound represented by formula (I), is used for treating cancer diseases, the medicinal composition contains a therapeutically effective amount of the parthenolide derivative (I) and a pharmaceutically acceptable carrier or other anticancer medicines, and the use of the derivative is an application of the derivative in medicines, especially an application in the preparation of cancer treatment medicines.

Description

technical field [0001] The present invention belongs to the technical field of medicines, and in particular, relates to parthenolide derivatives, a pharmaceutical composition for treating cancer or adjuvant treatment of tumors, a preparation method thereof, and a preparation method of the pharmaceutical compound and composition for anti-tumor therapy. Application in cancer or adjuvant anticancer drugs. Background technique [0002] Tumors are a great threat to human health. There are about 2 million cancer patients in my country, with 1.6 million new cases every year. This is a large group. Anti-tumor research is a very challenging and significant field in the field of life sciences today. . In the past, the treatment methods focused on the eradication and killing of cancer cells. At present, the commonly used antineoplastic drugs in clinical practice are mainly cytotoxic drugs. These anticancer drugs have disadvantages such as poor selectivity, strong toxic and side effects...

Claims

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Application Information

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IPC IPC(8): C07D493/04A61K31/365A61P35/00A61P35/02
CPCC07D493/04
Inventor 陈悦张泉杨忠金
Owner ACCENDATECH
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