Tetrazine substituent group-containing aromatic isoselenazole compound as well as synthesis method and application thereof

A compound and substituent technology, applied in the synthesis of aryl isoselenazole compounds, the application field of medicine, can solve the problems of peripheral neurotoxicity, bone marrow suppression, side effects, etc., and achieve good anti-tumor effect

Pending Publication Date: 2021-10-22
KEAISE MEDICINE WUHAN
View PDF12 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

First of all, the efficiency is not ideal
Secondly, there are many side effects, and patients may experience adverse reactions such as bone marrow suppression, gastrointestinal reactions, and peripheral ne...

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
  • Tetrazine substituent group-containing aromatic isoselenazole compound as well as synthesis method and application thereof
  • Tetrazine substituent group-containing aromatic isoselenazole compound as well as synthesis method and application thereof
  • Tetrazine substituent group-containing aromatic isoselenazole compound as well as synthesis method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0096] 3,4-Dihydro-3-methyl-4-oxo-N-(3(2H)-oxo-1,2-benzisoselazol-2-yl)-ethyl-imidazo[5 ,1-d]-1,2,3,5-tetrazine-8-carboxamide (No. 1)

[0097] 1) Add 28g of 2-aminobenzoic acid to a beaker, and add a mixture of 40mL of concentrated hydrochloric acid and 40mL of water, bathe in ice, keep the reaction temperature below 5°C, and slowly add NaNO dropwise 2 (18g dissolved in 40mL water), continue to react for 2 hours after dripping to obtain a diazonium salt solution, and set aside; take 100mL water and add 16g NaOH to it, place it at 50°C and stir to dissolve, then add Liandi Sodium sulfite 17.6g, add 16g selenium powder after clarification, continue to react for 3h after adding, make Na 2 Se 2 solution, set aside; under stirring conditions, the diazonium salt was added dropwise to Na 2 Se 2 In the solution, keep the reaction temperature below 5°C, and continue to react for 2 hours after the dripping, and ensure that the solution is alkaline. After the reaction was completed,...

Embodiment 2

[0105] 3,4-Dihydro-3-methyl-4-oxo-N-(3(2H)-oxo-5-fluoro-1,2-benzisoselenazol-2-yl)-ethyl- Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide (Code 2)

[0106] 1) Add 7.75g of 2-amino-5-fluorobenzoic acid to a beaker, and add a mixture of 15mL of concentrated hydrochloric acid and 15mL of water, in an ice bath, keep the reaction temperature below 5°C, and slowly add NaNO dropwise 2 (4.35g dissolved in 10mL water), continue to react for 2 hours after dripping, and prepare a diazonium salt solution for later use; take 30mL water and add 4g NaOH to it, place it at 50°C and stir to dissolve, then add a small amount of continuous Sodium disulfite 4.35g, after clarification, add 4g of selenium powder, continue to react for 2-3h after adding, and obtain Na 2 Se 2 solution, set aside; under stirring conditions, the diazonium salt was added dropwise to Na 2 Se 2 In the solution, keep the reaction temperature below 5°C, and continue to react for 2 hours after the dripping, and ensure tha...

Embodiment 3

[0114] 3,4-Dihydro-3-methyl-4-oxo-N-(3(2H)-oxo-6-fluoro-1,2-benzisoselenazol-2-yl)-ethyl- Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide (Code 3)

[0115] 1) Add 7.75g of 2-amino-6-fluorobenzoic acid to a beaker, and add a mixture of 15mL of concentrated hydrochloric acid and 15mL of water, in an ice bath, keep the reaction temperature below 5°C, and slowly add NaNO dropwise 2 (4.35g dissolved in 10mL water), continue to react for 2 hours after dripping, and prepare a diazonium salt solution for later use; take 30mL water and add 4g NaOH to it, place it at 50°C and stir to dissolve, then add a small amount of continuous Sodium disulfite 4.35g, add 4g selenium powder after clarification, continue to react for 3h after adding, make Na 2 Se 2 solution, set aside; under stirring conditions, the diazonium salt was added dropwise to Na 2 Se 2 In the solution, keep the reaction temperature below 5°C, and continue to react for 2 hours after the dripping, and ensure that the soluti...

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 tetrazine substituent-containing aromatic isoselenazole compounds as shown in a formula (I) and a formula (II) as well as a preparation method and application of the tetrazine substituent-containing aromatic isoselenazole compounds. The compound disclosed by the invention has the characteristic of targeting TrxR target spots, so that the compound has a good anti-tumor effect on tumors, especially brain glioma. The compound provided by the invention can well inhibit the growth of brain glioma cells in vivo and in vitro as a medicine.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a method for synthesizing aromatic and isoselenazole compounds containing a tetrazine substituent and its application in the preparation of drugs for treating tumors, especially brain gliomas . Background technique [0002] Glioma is a common orthotopic intracranial tumor, accounting for more than 50% of intracranial tumors, and its incidence is 1-3% of systemic malignant tumors. The median overall survival of patients is only 12-15 months. Since most gliomas grow infiltratingly and have no obvious histological boundary with normal brain tissue, it is very difficult to cure gliomas by surgical resection. In addition, radiation therapy (RT) is also commonly used clinically, including conventional radiotherapy, three-dimensional conformal radiotherapy, and stereotactic radiotherapy. However, glioma cells themselves are not sensitive enough to radiotherapy, and there are differ...

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
IPC IPC(8): C07D487/04A61K31/4188A61P35/00
CPCC07D487/04A61P35/00Y02P20/55A61P25/00
Inventor 曾慧慧焦文宣尹汉维
Owner KEAISE MEDICINE WUHAN
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