Square acid derivate and preparation method thereof

A technology of squaraine derivatives and medicinal salts, applied in the field of new anti-tumor compounds, which can solve the problems of easy isomerization and reduced activity

Inactive Publication Date: 2010-11-10
MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI +1
View PDF0 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

CA-4 is a cis-stilbene compound, one benzene ring has three methoxy groups (called A ring), and the other benzene ring has hydroxyl and methoxy groups (called B ring), but this cis The double bond linkage structure is easily isomerized into a thermodynamically more stable trans double bond during storage and use, thereby reducing the activity

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
  • Square acid derivate and preparation method thereof
  • Square acid derivate and preparation method thereof
  • Square acid derivate and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0092] Example 1: 3-(2',4'-dimethoxyphenyl)-4-(4-methoxyphenyl)-3-cyclobutene-1,2-dione (2)

[0093] Dissolve 0.36g (2.8mmol) of 3,4-dichloro-3-cyclobutene-1,2-dione in dichloromethane (6ml), cool to 0°C, and add AlCl 3 0.32g (2.4mmol), slowly drop 0.13g (1.2mmol) of methoxybenzene into the reaction solution, maintain 0°C for 1.5h, pour the reaction solution into crushed ice, and dichloromethane (15ml×2) Extracted, dried over anhydrous magnesium sulfate, spin-dried, and recrystallized from dichloromethane and n-hexane to obtain 0.54 g (50%) of a yellow solid, which was 3-chloro-4-(4-methoxyphenyl)-3- The crude product of cyclobutene-1,2-dione is used for the next reaction.

[0094] The crude product 3-chloro-4-(4-methoxyphenyl)-3-cyclobutene-1,2-dione 0.54g (2.4mmol) obtained in the previous step was dissolved in dichloromethane (6ml) and cooled to 0℃, add AlCl 3 0.32g (2.4mmol), slowly drop 0.33g (2.4mmol) of 1,3-dimethoxybenzene into the reaction solution, maintain 0°C ...

Embodiment 2

[0099] Example 2: 3-(4-methoxyphenyl)-4-(2',3',4'-trimethoxyphenyl)-3-cyclobutene-1,2-dione (3)

[0100] Using 1,2,3-trimethoxybenzene as raw material, instead of 1,3-dimethoxybenzene in Example 1, synthesized in a similar manner as in Example 1 to obtain 3-(4-methoxyphenyl)- 4-(2',3',4'-trimethoxyphenyl)-3-cyclobutene-1,2-dione (3).

[0101] The product was a yellow solid, m.p. 115-116°C.

[0102] 1 H NMR (CDCl 3 ): δ3.78(S, 3H), 3.92(S, 3H), 3.94(S, 3H), 3.99(S, 3H), 6.84(d, J=8.8Hz, 1H), 6.99(dd, J 1 =2.0Hz,J 2 =6.8Hz, 2H), 7.58(d, J=8.8Hz, 1H), 8.01(dd, J 1 =2.0Hz,J 2 = 6.8Hz, 2H).

[0103] 13 C NMR (CDCl 3 ): δ55.5, 56.3, 61.2, 61.4, 107.3, 114.1, 115.7, 121.8, 124.6, 131.6, 142.2, 151.8, 157.5, 163.7, 183.6, 186.3, 195.9, 197.2.

[0104] Elemental Analysis: C 20 h 18 o 6 .

[0105] Calculated: C, 67.79; H, 5.12; Found: C, 67.40; H, 5.16.

Embodiment 3

[0106] Example 3: 3-(4-methoxyphenyl)-4-(2',4',6'-trimethoxyphenyl)-3-cyclobutene-1,2-dione (4)

[0107] Using 1,3,5-trimethoxybenzene as a raw material, 3-(4-methoxyphenyl)-4-(2',4',6'-trimethoxybenzene was synthesized in a similar manner to Example 2 base)-3-cyclobutene-1,2-dione (4). The product was a yellow solid, m.p. 185-187°C.

[0108] 1 H NMR (CDCl 3 ): δ3.77 (S, 6H), 3.90 (S, 3H), 3.92 (S, 3H), 6.23 (S, 2H), 6.96 (dd, J 1 =2.0Hz,J 2 =6.8Hz, 2H), 7.92(dd, J 1 =2.0Hz,J 2 = 6.8Hz, 2H).

[0109] 13 C NMR (CDCl 3 ): δ55.5, 55.6, 55.8, 90.8, 100.7, 113.9, 122.6, 131.5, 158.8, 163.3, 165.1, 184.6, 186.9, 195.9, 198.0.

[0110] Elemental Analysis: C 20 h 18 o 6 .

[0111] Calculated: C, 67.79; H, 5.12; Found: C, 67.74; H, 5.14.

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 square acid derivate and pharmaceutical salt thereof. The square acid derivate has a structure shown as the formula (I). The square acid derivate can be taken as micro-molecular tubulin inhibitor, having the function of resisting microtubule and remarkable anti-tumor activity and the advantages of small molecular weight, simple synthesis and small toxic and side effects. The invention further provides a synthesis method of the square acid derivate and an anti-tumor medical composite taking the square acid derivate and the pharmaceutical salt thereof as active components.

Description

technical field [0001] The invention relates to a novel antitumor compound, which is a squaraine derivative; the invention also relates to a synthesis method of the squaraine derivative and its application in antitumor. Background technique [0002] Tumor is a common and frequently-occurring disease that seriously threatens human life, and its mortality rate ranks second only to cardiovascular diseases. Anti-mitotic agents are an important class of anti-tumor drugs. Their unique mechanism of action and good therapeutic effect make them a hot spot in anti-tumor research. [0003] Microtubules are one of the main structural components of the cytoskeleton. They exist in the cytoplasm of almost all eukaryotes and are composed of tubulin and microtubule-binding proteins. Microtubules have the dynamic characteristics of polymerization and depolymerization, and play an important role in maintaining cell shape, cell division and proliferation, the composition and transportation of ...

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): C07C49/753C07C205/45C07C69/12C07C225/22C07D209/08C07C45/64C07C201/12C07C67/29C07C221/00A61K31/122A61K31/222A61K31/136A61K31/404A61P43/00A61P35/00A61P35/02
Inventor 刘宗英大卫·W·博伊金王跃明李卓荣蒋建东
Owner MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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