Fluorinated olefin analogue of marine natural product cyclic depsipeptide as well as preparation method and application of fluorinated olefin analogue

A kind of technology of fluorinated olefin and compound, applied in the field of antitumor therapeutic agent

Inactive Publication Date: 2017-05-17
FUDAN UNIV
View PDF2 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the research on Largazole fluorinated analogs has not been reported yet. A large number of new drug development studies have found that introducing F elements into active molecules can often increase their activity and metabolic stability in vivo. The reasons are: 1. The concentration of fluorine atoms and hydrogen atoms The size is very close, and the molecular size and shape hardly change after the introduction; 2. The introduction of fluorine atoms makes the non-polar carbon-carbon double bond (C=C) polar; 3. The strongly negative F atom can participate in Form hydrogen bonds; 4. The introduction of fluorine atoms can produce a strong lipophilic effect, especially conducive to the penetration of cell membranes; 5. The introduction of an F atom on the double bond will be more stable than the ordinary C=C double bond and resistant to enzymes more sexual

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
  • Fluorinated olefin analogue of marine natural product cyclic depsipeptide as well as preparation method and application of fluorinated olefin analogue
  • Fluorinated olefin analogue of marine natural product cyclic depsipeptide as well as preparation method and application of fluorinated olefin analogue
  • Fluorinated olefin analogue of marine natural product cyclic depsipeptide as well as preparation method and application of fluorinated olefin analogue

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 117

[0076] Example 1 Synthesis of Largazole Fluorinated Analogs in 17R-Z Configuration

[0077]

[0078] The first step prepares compound 2:

[0079]

[0080] Add the compound trityl mercaptan (1.28g, 4.62mmol) and 20ml of anhydrous dichloromethane into a 100ml dry reaction flask, stir and dissolve at room temperature, add triethylamine (0.9ml, 6.50mmol), and then add acrolein dropwise (0.43ml, 6.50mmol), stirred at room temperature for 1h (TLC tracking). The stirring was stopped, and the solvent was spin-dried to obtain a white crude product, which was directly used for the preparation of compound 2 without further purification. R f =0.13(PE:EA=40:1). 1 H-NMR (400MHz, CDCl3): δ9.56 (brs, 1H), 7.23–7.43 (m, 15H), 2.47 (t, J = 7.0Hz, 2H), 2.37 (t, J = 6.7Hz, 2H) .

[0081] The second step prepares compound 3:

[0082]

[0083] Add PPh to a 100ml dry reaction vial 3 (3.15g, 12.0mmol), ethyl dibromofluoroacetate (0.83ml, 6.0mmol) and 30ml of anhydrous THF were stirred...

Embodiment 2

[0110] Example 2 Synthesis of Largazole Fluorinated Analogs in 17S-Z Configuration

[0111]

[0112] Prepare and synthesize Largazole fluorinated analogues of 17S-Z configuration according to the method and experimental procedures of Example 1, wherein, in the fifth step, chiral alcohol S of corresponding configuration is prepared with the chiral prosthetic raw material of the opposite configuration -5, or the S-5 isomer separated and purified in the fifth step, other experimental methods are the same; the Largazole fluorinated analogue of the prepared 17S-Z configuration: HRMS-ESI(M / Z):[M+Na] + Calcd.for C 40 h 41 FN 4 o 4 S 3 Na:663.2115,found:663.2139.

Embodiment 3

[0114] Some compounds of the present invention use the SRB method to EBC-1 (human lung cancer cell line, c-Met gene amplification), EBC-1 / SR (human lung cancer cell line, c-Met gene amplification, SGX-523 drug resistance strain) and NCI-H3122 (human lung cancer cell line, EML4-ALK (variant1)), the effect on cell proliferation (72 hours) was investigated respectively, and compared with the clinically used drug SAHA.

[0115] It includes the steps: cells in the logarithmic growth phase are inoculated to a 96-well culture plate at an appropriate density, 90 μL per well, and after overnight culture, different concentrations of drugs are added for 72 hours, and each concentration is set in triplicate. Vehicle control and cell-free zero wells. After the effect, the adherent cells poured out the culture medium, added 10% (w / v) trichloroacetic acid (100 μL / well) and fixed at 4°C for 1 hour, then washed five times with distilled water, dried at room temperature, and added SRB solution ...

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 belongs to the pharmaceutical field and relates to a novel fluorinated olefin analogue of marine natural product cyclic depsipeptide (namely marine natural product Largazole), in particular to a compound shown in the general formula (1) or salt and a preparation method of the compound as well as a drug containing the compound or application of the compound serving as an anti-tumor therapeutic agent.

Description

technical field [0001] The invention relates to the field of pharmacy, and relates to a fluorinated analogue of a new marine natural product cyclic ester peptide (namely, a marine natural product Largazole), a preparation method thereof, and a medicine containing the compound or its composition as an antitumor therapeutic agent. Background technique [0002] According to data, cancer has become another major disease that endangers human health after cardiovascular and cerebrovascular diseases since its discovery to today. Since the 1970s, the number of cancer incidence and death in my country has been on the rise. The annual incidence of tumors will reach 3 million person-times, and the annual death toll will reach 2.5 million person-times. Cancer has become the leading cause of death among urban residents in my country. Therefore, research and discovery of low-toxicity and high-efficiency tumor treatment drugs are of great importance. commercial value. [0003] There are man...

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): C07D513/18A61K31/429A61P35/00
CPCC07D513/18Y02P20/55
Inventor 雷新胜单广胜张冰冰李洋于晓琳
Owner FUDAN UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap