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

Arg-Tyr modified aliphatic amine/ alcohol derivatives and preparation method and application thereof

A reaction and compound technology, applied in the field of artificially synthesized polypeptide compounds, can solve problems such as poor oral activity

Inactive Publication Date: 2012-11-28
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
View PDF6 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the design of analgesics, the inventors realized that the Kyoto phenol reverse sequence (Arg-Tyr) is a potential analgesic dipeptide, and that it has poor oral 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
  • Arg-Tyr modified aliphatic amine/ alcohol derivatives and preparation method and application thereof
  • Arg-Tyr modified aliphatic amine/ alcohol derivatives and preparation method and application thereof
  • Arg-Tyr modified aliphatic amine/ alcohol derivatives and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Example 1 prepares N G -Arg(NO 2 )

[0022] Under the condition of ice-salt bath stirring, add 80ml concentrated nitric acid to 500ml eggplant bottle, then slowly add 80ml concentrated sulfuric acid. After 10 min, 47.33 g (272 mmol) of L-Arg was added in batches, and the reaction mixture was stirred and reacted for 2 h in an ice-salt bath. Slowly add 96ml of ice water to the reaction mixture, then slowly add concentrated ammonia water, adjust the pH to 8, then adjust the pH to 6 with glacial acetic acid, a large amount of colorless solid precipitates, put it in a refrigerator at 4°C to continue crystallization. Filter under reduced pressure, discard the filtrate, dissolve the filter cake with hot water at 80°C, and put it in a refrigerator at 4°C for recrystallization. Filter under reduced pressure at room temperature to collect 52.5 g of insoluble matter as a colorless solid with a yield of 88%. ESI-MS (m / e): 220 [M+H] + .

Embodiment 2

[0023] Embodiment 2 prepares N α -Boc-N G -Arg(NO 2 )

[0024] Weigh 1.752g N G -Arg(NO 2 ) into the reaction bottle, add 3ml of water to dissolve, under the condition of ice bath, slowly add 8ml of 1N NaOH dropwise, will dissolve 1.92g (Boc) 2 Slowly pour the dioxane of O into it, adjust the pH of the reaction solution to 9, and react for 48 hours. During this period, the CO in the reaction system is pumped every 2 hours 2 once. After the reaction is complete as detected by TLC, adjust the pH of the reaction solution to 7, spin off dioxane, then adjust the pH of the reaction solution to 2, extract the reaction solution three times with ethyl acetate, and then wash the ethyl acetate layer three times with saturated NaCl , to obtain the ethyl acetate layer with anhydrous NaSO 4 Dry overnight, filter to remove NaSO 4 , spin-dried ethyl acetate to obtain 2.4 g of the title compound as a colorless solid, yield 94%. ESI-MS (m / e): 320 [M+H] + .

Embodiment 3

[0025] Embodiment 3 prepares Tyr-OMe

[0026] Put 120ml of anhydrous methanol into the reaction flask, add 10.4ml of thionyl chloride dropwise under stirring in an ice bath, and dropwise add 7.24g (40mmol) of L-Tyr in batches within 30min, and stir the reaction mixture at room temperature for 24 hours, thin Layer chromatography was monitored until the disappearance of the starting material. The water pump decompressed and drained the reaction liquid, added methanol to dissolve, drained, and repeated 3 times; added ether, drained, and repeated 3 times. Recrystallized from methanol-ether, and filtered to obtain 8.78 g of the title compound as a colorless solid, with a yield of 87%. ESI-MS (m / e): 196 [M+H] + .

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 discloses Arg-Tyr modified aliphatic amine / alcohol derivatives and a preparation method thereof and application thereof as anodynes and anti-inflammatory agents. The structure of the Arg-Tyr modified aliphatic amine / alcohol derivatives is shown as a general formula I, namely Arg-TyrXCH2(CH2)nCH3, wherein in the formula, X is NH or O; and n is 6, 8, 10, 12, 14 or 16. The pain relieving activity of the compounds in the general formula is evaluated by adopting a mouse heat thrilling process model, the anti-inflammatory activity of the compounds in the general formula I is evaluated by adopting a mouse ear swelling model, and experimental results show that the 12 compounds represented by the general formula I have excellent pain relieving effect and high anti-inflammatory activity under the same dose and can be applied to production of analgesics and anti-inflammatory medicaments.

Description

technical field [0001] The present invention relates to an artificially synthesized polypeptide compound, in particular to a compound obtained by protecting and modifying the carboxyl end of dipeptide with fatty amine and fatty alcohol, its preparation method and its application in the preparation of analgesic and anti-inflammatory drugs . Background technique [0002] As one of the main vital signs of human beings, pain has important biological significance. The World Pain Conference recognized pain as the "fifth vital sign of human beings" after breathing, pulse, body temperature and blood pressure, and many patients are suffering from pain. At present, the analgesics used clinically all have their own toxic and side effects, such as the addiction of opioid analgesics and the irritation of salicylic analgesics to the gastrointestinal tract. Finding analgesics is a hot spot in the research of new drugs one. In the design of analgesics, the inventors realized that Kyoto p...

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): C07K5/068C07K1/06A61K38/05A61P29/00
Inventor 赵明彭师奇于言言
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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