Unlock instant, AI-driven research and patent intelligence for your innovation.

Synthesis and preparation method of a class of novel curcumin derivatives, and application of novel curcumin derivatives in cancer treatment

A curcumin, biological technology, applied in the field of tumor drug research and development, can solve problems such as poor water solubility, limited application and research of Curcumin, and short half-life.

Active Publication Date: 2020-06-09
HENAN RADIOMEDICAL SCI & TECH CO LTD
View PDF2 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the poor water solubility and the short half-life of the drug in the body, resulting in low bioavailability of the compound in vivo, the application and research of Curcumin are obviously limited

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Synthesis and preparation method of a class of novel curcumin derivatives, and application of novel curcumin derivatives in cancer treatment
  • Synthesis and preparation method of a class of novel curcumin derivatives, and application of novel curcumin derivatives in cancer treatment
  • Synthesis and preparation method of a class of novel curcumin derivatives, and application of novel curcumin derivatives in cancer treatment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0092] Embodiment 1: the synthesis of compound 1a-1f

[0093] Refer to process 1

[0094]

[0095] 1a: X=-CH2-, Y=-(CH 2 ) 2 -, L=C, E=C, Z=C, D=C

[0096] 1b: X=-CH2-, Y=-(CH 2 ) 2 -, L=C, E=C, Z=C, D=C

[0097] 1c: X=-CH2-, Y=-(CH 2 ) 2 -, L=C, E=C, Z=C, D=C

[0098] 1d: X=-CH2-, Y=-(CH 2 ) 2 -, L=N, E=C, Z=C, D=C

[0099] 1e: X=-CH2-, Y=-CH 2 -, L=N, E=C, Z=N, D=C

[0100] 1f: X=-CH2-, Y=-(CH 2 ) 2 -, L=N, E=N, Z=C, D=C

[0101] The specific synthesis method, taking compound 1a as an example, the structural formula is as follows:

[0102]

[0103] The name of compound 1a is (1E, 6E)-1-(4-hydroxy-3-methoxyphenyl)-7-(3-methoxy-4-(4-(2-(piperidin-1-yl) ) ethoxy) benzyloxy) phenyl) -1,6-heptadiene-3,5-dione, its synthetic route is as follows:

[0104]

[0105] Step 1. (1E,6E)-1-(4-Hydroxy-3-methoxyphenyl)-7-(3-methoxy-4-(4-(2-(piperidin-1-yl) Ethoxy)benzyloxy)phenyl)-1,6-heptadiene-3,5-dione (1a)

[0106] Curcumin (1) (300mg, 0.814mmol, 1....

Embodiment 2

[0109] Embodiment 2: the synthesis of compound 1g-1i

[0110] Refer to process 2

[0111]

[0112] 1g: X=-CH2-, Y=-(CH 2 ) 2 -, Z=O, D=C, E=C

[0113] 1h: X=-CH2-, Y=-(CH 2 ) 2 -, Z=O, D=N, E=C

[0114] 1i: X=-CH2-, Y=-(CH 2 ) 2 -, Z=N, D=C, E=C

[0115] The specific synthesis method, taking compound 1g as an example, the structural formula is as follows:

[0116]

[0117] The name of compound 1g is (1E, 6E)-1-(4-(5-(2--cyclohexylimino)furan)-3-methoxyphenyl)-7-(4-hydroxyl-3-methyl Oxyphenyl)-1,6-heptadiene-3,5-dione, its synthetic route is as follows:

[0118]

[0119] Step 1. (1E,6E)-1-(4-(5-(2-cycloheximino)furan)-3-methoxyphenyl)-7-(4-hydroxy-3-methoxy phenyl)-1,6-heptadiene-3,5-dione (1g)

[0120] Curcumin (1) (300mg, 0.814mmol, 1.0eq), 1-(2-(5-(chloromethyl) furyloxy) ethyl) cycloheximide (231mg, 0.896mmol, 1.1eq) and Potassium carbonate (225mg, 1.63mmol, 2.0eq) was dissolved in N,N-dimethylformamide (10mL), and reacted at 25°C for 36 hours. ...

Embodiment 3

[0123] Embodiment 3: the synthesis of compound 2a-2f

[0124] Refer to process 3

[0125]

[0126] 2a: X=-CO-, Y=-(CH 2 ) 2 -, L=C, E=C, Z=C, D=C

[0127] 2b: X=-CO-, Y=-(CH 2 ) 2 -, L=C, E=C, Z=C, D=C

[0128] 2c: X=-CO-, Y=-(CH 2 ) 2 -, L=C, E=C, Z=C, D=C

[0129] 2d: X=-CO-, Y=-(CH 2 ) 2 -, L=N, E=C, Z=C, D=C

[0130] 2e: X=-CO-, Y=-CH 2 -, L=N, E=C, Z=N, D=C

[0131] 2f: X=-CO-, Y=-(CH 2 ) 2 -, L=N, E=N, Z=C, D=C

[0132] The specific synthesis method, taking compound 2a as an example, the structural formula is as follows:

[0133]

[0134] The name of compound 2a is 4-((1E,6E)-7-(4-hydroxy-3-methoxyphenyl)-3,5-dioxo-1,6-heptadien-1-yl) -2-methoxyphenyl-4-(2-(piperidin-1-yl)ethoxy)phenyl ester, its synthetic route is as follows:

[0135]

[0136] Step 1. 4-((1E,6E)-7-(4-Hydroxy-3-methoxyphenyl)-3,5-dioxo-1,6-heptadien-1-yl)-2 -Methoxyphenyl-4-(2-(piperidin-1-yl)ethoxy)phenyl ester (2a)

[0137] Curcumin (1) (300mg, 0.814mmol, 1.0eq)...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides a preparation method of a class of novel curcumin derivatives, and application of the compounds in the fields of chemistry, biology and medicine. According to the invention, experimental results show that the curcumin derivative provided by the invention is improved in solubility and in-vivo bioavailability in comparison with a curcumin raw drug, is also remarkably enhancedin antitumor activity, and has strong binding activity with a biological target STAT3 protein related to cancer in a human body; the results of a cell proliferation experiment (CCK-8) show that the compound disclosed by the invention can obviously inhibit proliferation of non-small cell lung cancer cell strains PC9 and HCC827, and particularly has a strong proliferation inhibition effect on PC9GR,PC9AR, HCC827AR and HCC827ER cells which respectively have resistance to Gefitinib, Afatinib or Erlotinib; and the research is of great significance to the application of the compound in tumor clinical treatment and other biological aspects.

Description

technical field [0001] The invention belongs to the technical field of tumor original drug research and development, and in particular relates to a curcuminoid compound and a biologically acceptable salt thereof, a preparation method and an application thereof. Background technique [0002] According to the latest cancer data in China released by the National Cancer Center in 2017, in China, there are 4.29 million new cancer cases each year, accounting for 20% of the global new cases, and 2.81 million deaths (Chinese Cancer Clinic and Rehabilitation, 2017 (5): 574-574). In 2017, the five new anti-cancer drugs approved by CFDA in China did not have an innovative target, and there were very few original targeted new drugs in China, which generally reflected that the research and development level of domestic targeted original drugs lagged behind that of Europe and the United States. How to achieve "double innovation" (disease-related new targets and new compounds for clinical...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D295/088C07D213/79C07D239/34C07D237/24C07D237/14C07D263/42C07D207/36C07D307/58C07D213/65C07C217/20C07C217/22C07C213/08A61P35/00A61P35/02A61K31/5375A61K31/5377A61K31/4453A61K31/55A61K31/506A61K31/454A61K31/50A61K31/138
CPCA61P35/00A61P35/02C07C217/20C07C217/22C07D207/36C07D213/65C07D213/79C07D237/14C07D237/24C07D239/34C07D263/42C07D295/088C07D307/58
Inventor 徐学军杨玉坡杨争艳朱艳霞段超群曹艳艳张韶华刘瑞徐春萍
Owner HENAN RADIOMEDICAL SCI & TECH CO LTD