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

Selenium-containing isoxazolyl amine compound and preparation method and application thereof

A compound, azolamide technology, applied in the field of medicine, can solve problems such as long-term use limitation and reduction of comprehensive therapeutic index

Active Publication Date: 2020-02-04
SHANGHAI XINGYE PHARM TECH CO LTD
View PDF5 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, despite these clinical benefits, their long-term use is limited mainly by their clinical toxicity, including peripheral neuropathy, lethargy, constipation, and the risk of thromboembolism and teratogenicity, thus greatly reducing their combined therapeutic index

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
  • Selenium-containing isoxazolyl amine compound and preparation method and application thereof
  • Selenium-containing isoxazolyl amine compound and preparation method and application thereof
  • Selenium-containing isoxazolyl amine compound and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0084] Synthesis of Example 1 Compound 1

[0085] Preparation Method Step 1: Preparation of 2-Chloroselenyl Benzoyl Chloride

[0086] Anthranilic acid (1.37 g, 10 mmol) was added to 3 N hydrochloric acid aqueous solution (4 ml) under ice-cooling, and then an aqueous solution containing 690 mg of sodium nitrite (10 mmol) was slowly added dropwise with stirring 2 ml, react for 1 hour until clarified, and set aside.

[0087] Under the protection of nitrogen, 790 mg (10 mmol) of selenium powder and 20 mg of cetyltrimethylammonium bromide were weighed and added to 2 N aqueous sodium hydroxide solution (5 ml) to obtain a Se-NaOH solution. Then put NaOH (40 mg, 1 mmol) and NaBH under ice bath 4 (49 mg, 1.3 mmol) in water (1 ml) was added to the above Se-NaOH solution, and stirred at room temperature for 1 hour, then warmed to 90 o C continued to stir and react for half an hour to obtain a sodium diselenide solution. After cooling to room temperature, the 2-benzoic acid diazonium ...

Embodiment 22

[0095] The synthesis of embodiment 22 compound 19

[0096] Synthetic route 1:

[0097]

[0098] Preparation step 1 : intermediate a19 synthesis

[0099] Add o-iodine slowly to a THF solution (10 mL) containing 3-amino-1-adamantanol (167 mg, 1 mmol) and triethylamine (151 mg, 1.5 mmol) under stirring in an ice bath Benzoyl chloride (266 mg, 1 mmol) and continue to react for 1~2 h to complete. After the reaction was detected by TLC, 20 ml of water was added, followed by ethyl acetate (20 mL×2) for extraction, the organic phase was washed successively with saturated brine, dried over anhydrous sodium sulfate, filtered, and the obtained filtrate was evaporated to dryness under reduced pressure and passed through a silica gel column. Chromatographic purification (V 乙酸乙酯 :V 石油醚 =1:4~1:1), the reaction was quantified to obtain a19. MS-ESI [M+H] + 398.0 (397.0).

[0100] Preparation step 2 : Synthesis of Compound 19

[0101] Containing a19 (397 mg, 1 mmol), selenium po...

Embodiment 30

[0104] Example 30 Synthesis of Compound 3

[0105] Add 10% Pd / C to a methanol solution (1 mL) containing compound 2 (72 mg, 0.2 mmol), then place under H 2 Heated to 70°C in the atmosphere for 48 hours to complete the reaction. After the reaction was detected by TLC, it was filtered, and the obtained filtrate was evaporated to dryness under reduced pressure and purified by column chromatography to obtain compound 6 (25 mg, 36%). HRMS-ESI: m / z calcd for C 12 h 10 N 2 o 3 Se:324.9966, found [M+H] + 326.0040; 1 H NMR (400 MHz, DMSO- d 6 ) δ 10.97 (s, 1H), 7.47– 7.34 (m, 1H), 7.05 – 6.83 (m, 2H), 6.33 (brs, 2H), 5.23 (dd, J = 12.8, 5.3Hz, 1H), 2.92 – 2.83 (m, 1H), 2.59 (d, J = 17.3 Hz, 1H), 2.45 – 2.35 (m, 1H), 2.12– 2.02 (m, 1H).

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 selenium-containing isoxazolyl amine compound with a structure shown in a formula I. Tests show that the compound can effectively inhibit TNF-alpha activity and regulate ferroptosis. The invention further provides a preparation method of an inhibitor and application to preparation of medicine for preventing and treating TNF-alpha and ferroptosis-mediated diseases.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a class of selenium-containing isoxazole amine compounds with TNF-α and / or ferroptosis regulating activity and pharmaceutically acceptable salts, solvates, crystal forms, stereoisomers and isotope compounds thereof or metabolites. The present invention also relates to methods for the preparation of these compounds, and the use of these compounds as TNF-α and or ferroptosis modulators in the treatment and / or prevention of diseases or disorders associated with TNF-α and ferroptosis pathways in humans or other mammals the use of. Background technique [0002] TNF-α (Tumor Necrosis Factor) is a type of cytokines discovered in the 1970s with various biological effects, mainly secreted by activated monocytes / macrophages / T cells, through specific receptors on the cell membrane For example, by activating the three signaling pathways of Caspase protease, JNK and transcription factor NF-κ...

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): C07D401/04C07D421/14C07D421/04C07D293/10A61P19/02A61P29/00A61P1/00A61P3/10A61P17/06A61P19/08A61P31/14A61P31/18A61P31/20A61P25/28A61P35/02A61P35/00A61P37/06A61K31/454A61K31/4439A61K31/5377A61K31/41
CPCC07D401/04C07D421/14C07D421/04C07D293/10A61P19/02A61P29/00A61P1/00A61P3/10A61P17/06A61P19/08A61P31/14A61P31/18A61P31/20A61P25/28A61P35/02A61P35/00A61P37/06A61K31/41A61K31/4439A61K31/454A61K31/5377C07D499/80
Inventor 宋维彬柳艳辉
Owner SHANGHAI XINGYE PHARM TECH CO LTD
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