Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Composition of 5-nitrobenzoate derivatives as Anti-metastatic agent that inhibits tumor cell-induced platelet aggregation

a technology of tcipa and derivatives, which is applied in the field of 5nitrobenzoate derivatives, can solve the problems of inability to show specificity, inability to inhibit aspirin, and complicated details of tcipa, and achieve the effect of inhibiting tcipa and inhibiting platelet aggregation

Inactive Publication Date: 2014-01-09
CHANG GUNG UNIVERSITY
View PDF1 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention provides a series of 5-nitrobenzoate derivatives that can effectively inhibit tumor cells without affecting platelet aggregation. These compounds specifically target a surface protein called podoplanin, which plays a role in inducing platelet aggregation. Therefore, these compounds can be used as targeted therapy drugs for inhibiting tumor cells.

Problems solved by technology

Based on these results, the detail mechanism of TCIPA seems to very complicated and still be obscured.
Nevertheless, high dose aspirin does not show specificity and does not have effects on cancer metastasis and patient protection in clinics (Jurasz et al., Br. J. Pharmacol. 143: 819-826, 2004).
Antibody therapy is usually expensive and patients might suffer from the risk of autoantibody generation (Nakazawa et al., Cancer Sci. 102: 2051-2057, 2011).
On the whole, the problems in the prior art lie in that the functions of platelet aggregation are still influenced such that tumor cells cannot be specifically inhibited and TCIPA is not efficiently inhibited.

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
  • Composition of 5-nitrobenzoate derivatives as Anti-metastatic agent that inhibits tumor cell-induced platelet aggregation
  • Composition of 5-nitrobenzoate derivatives as Anti-metastatic agent that inhibits tumor cell-induced platelet aggregation
  • Composition of 5-nitrobenzoate derivatives as Anti-metastatic agent that inhibits tumor cell-induced platelet aggregation

Examples

Experimental program
Comparison scheme
Effect test

embodiment 1

of N-(2-benzamidoethyl)-2-hydroxy-5-nitrobenzamide

[0028]The preparation procedure of N-(2-benzamidoethyl)-2-hydroxy-5-nitrobenzamide is represented by the following formula II.

[0029]1-Chloro-4-nitro-2-(trifluoromethyl)benzene (2.0 mL, 13.3 mmole) was dissolved in dimethyl sulfoxide (DMSO, 12 mL), NaOH (1.6 g) was batchwise added at a temperature lower than 25° C., and the reaction solution was reacted at room temperature (RT) for 8 hours. After the reaction was terminated, the pH of the reaction solution was adjusted to 1.0 using concentrated HCl, and then the reaction solution was poured into the separatory funnel and extracted with CH2Cl2 for five times (each for 20 ml). The obtained CH2Cl2 solution was hydrated over MgSO4 and concentrated under vacuum. The obtained concentrate was subjected to the purification of silica gel column (50 g) and eluted with the system of CHCl3 / n-hexane (2:1) to afford compound 1 (1.85 g), yield of about 67%.

[0030]Compound 1: 1H NMR (400 MHz, CDCl3): ...

embodiment 2

of Other 5-nitrobenzoate Derivatives

[0041]For affording other 5-nitrobenzoate derivatives, compound 3 may be reacted with benzoyl chlorides bound with a various of substituted groups, such as mono-substituted benzoyl chloride, di-substituted benzoyl chloride or tri-substituted benzoyl chloride

respectively), and each of R1, R2, R3, R4, R5 and R6 may be fluoride, chloride, bromide, iodide or methyl group, and R1 to R6 may be bound to the para-, meta- or ortho-position of the benzoyl moiety. That is, the benzoyl moiety of the prepared compound 4 may be substituted as mono-substituted benzoyl moiety, di-substituted benzoyl moiety or tri-substituted benzoyl moeity

respectively).

embodiment 3

of 4-O-benzoyl-3-methoxy-β-nitrostyrene (compound 5)

[0042]trans-4-Hydroxyl 3-methoxyl-β-nitrostyrene and benzoyl chloride, were dissolved in a mixture solution of pyridine (1 ml) and CH2Cl2 (10 ml), and reacted at RT for 24 hours. After the removal of solvent, the obtained concentrate was subjected to the purification of silica gel column (90 g) and eluted with the system of n-hexane / acetone (3:1) to afford 4-O-benzoyl-3-methoxy-β-nitrostyrene (compound 5; as represented by formula III).

[0043]Compound 5: 1H NMR (400 MHz, CDCl3): δ 8.25 (1H, s), 8.24 (1H, s), 8.02 (1H, d, J=13.6 Hz), 7.68(1H, d, J=7.6 Hz), 7.61(1H, d, J=13.6 Hz), 7.56(1H, d, J=7.6 Hz), 7.55(1H, d, J=7.6 Hz), 7.28(1H, d, J=8.2 Hz), 7.24(1H, d, J=8.2 Hz), 7.17 (1H, d , J=1.2 Hz), 3.88 (3H, s). ESI-MS m / z 322 (100) [M+Na]+.

[0044]Compound 5 was nominated as 4-O-benzoyl-3-methoxy-β-nitrostyrene).

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

PropertyMeasurementUnit
aggregationaaaaaaaaaa
tumor cell-induced platelet aggregationaaaaaaaaaa
molecular weightaaaaaaaaaa
Login to View More

Abstract

Disclosed are 5-nitrobenzoate derivatives of Formula I,and the preparation method therefor, wherein R is referred to hydrogen (H), unsubstituted, mono-substituted, di-substituted or tri-substituted benzoyl moiety. 5-Nitrobenzoate derivatives of Formula I do not affect the platelet aggregation, possesses the inhibitory activity related to the tumor cell-induced platelet aggregation (TCIPA), and further specifically inhibits podoplanin-induced platelet aggregation. Therefore, 5-nitrobenzoates of the invention are applicable in its therapeutic use as the novel therapeutic agent in preventing tumor metastasis.

Description

CROSS-REFERENCE TO RELATED APPLICATION AND CLAIM OF PRIORITY[0001]The application claims the benefit of Taiwan Patent Application No. 101124690, filed on Jul. 9, 2012, in the Taiwan Intellectual Property Office, the disclosures of which are incorporated herein in their entirety by reference.FIELD OF THE INVENTION[0002]The present invention relates to a 5-nitrobenzoate derivative which is used in the therapy for cancer metastasis via the inhibition of tumor cell-induced platelet aggregation (TCIPA).BACKGROUND OF THE INVENTION[0003]Tumor cells can stimulate platelet activation and form the aggregation complex with platelets in the vascular circulation system. This interaction is termed as tumor cell-induced platelet aggregation (TCIPA). The ability of tumor cells to induce platelet aggregation has been proven to highly correlate with the metastatic capability of malignant tumor. At present, it is known that there are many factors and mechanisms involved in TCIPA. For instance, tumor c...

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(United States)
IPC IPC(8): C07C233/65
CPCC07C233/65A61K31/166A61P7/02A61P35/00C07C235/60C07C231/08
Inventor TSENG, CHING-PINGHSIEH, PEI-WENCHANG, YAO-WEN
Owner CHANG GUNG UNIVERSITY
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com