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

Preparation method for P<1>, P<4>-di(uridine5'-)tetraphosphate

A technology of tetraphosphate and uridine is applied in the field of preparation of P1,P4-ditetraphosphate, and can solve the problems such as the method that cannot be used in practice and the low yield of target product.

Pending Publication Date: 2019-09-10
JIANGSU HENGRUI MEDICINE CO LTD +1
View PDF6 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] No catalyzer is used in the preparation method disclosed by CN1147502C, but the yield of the target product is extremely low, and it cannot become a practical method

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
  • Preparation method for P&lt;1&gt;, P&lt;4&gt;-di(uridine5'-)tetraphosphate
  • Preparation method for P&lt;1&gt;, P&lt;4&gt;-di(uridine5'-)tetraphosphate
  • Preparation method for P&lt;1&gt;, P&lt;4&gt;-di(uridine5'-)tetraphosphate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 P 1 ,P 4 - Preparation of two (uridine 5'-) tetraphosphate

[0030] The preparation (UMP-TBA) of the compound shown in step 1. intermediate formula (IIa)

[0031] Add uridine-5'-monophosphate disodium salt (5.43mol, 2.0kg) and purified water (10.0kg) into a 20L plastic bucket, dissolve completely under stirring and filter, and the filtrate is set aside; convert 20.0L into hydrogen form The DOWEX IR100S resin was loaded into the chromatography column, rinsed with purified water (40.0kg), compacted the resin, exhausted the washing liquid after discharging air bubbles, and turned off the drain switch; slowly introduced the above filtrate into the column to make the upper layer liquid The surface is just submerged in the resin, and after standing still, add purified water (95.0kg) to the column for elution. When the pH of the eluent becomes 6.5-7.5, stop the elution, combine the eluent, and add it to a 200L reaction kettle , started stirring, and added tri-n-bu...

Embodiment 2

[0036] Example 2P 1 ,P 4 - Preparation of two (uridine 5'-) tetraphosphate

[0037] Take the prepared N,N-dimethylformamide solution of UTP-3TBA (UTP-3TBA 3.84g, 3.69mmol) and place it in a 100ml three-necked flask, add diisopropylcarbodiimide (564mg, 4.44mmol) , N 2 After 2 replacements, react at 25-30°C for 5 hours. Add UMP-TBA in N,N-dimethylformamide solution (UMP-TBA 2.23g, 4.43mmol) and anhydrous magnesium chloride (422mg, 4.43mmol) to the reaction solution, then react at 25-30°C for 5 hours, Sampling HPLC detection, area normalization method to calculate UP4U content and large molecular weight impurity P 1 , P 5 Di(uridine 5′-)pentaphosphate (UP5U) and P 1 , P 6 - Content of bis(uridine 5'-)hexaphosphate (UP6U).

[0038] result:

[0039]

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 preparation method for P<1>, P<4>-di(uridine5'-)tetraphosphate. Specifically, the method has a high yield in an industrial production process, enables the amount of generationof large molecular weight impurities which are difficult to be removed to be significantly reduced, is easy in purification, and provides possibility for industrial production of the P<1>,P<4>-di(uridine5'-)tetraphosphate.

Description

technical field [0001] This application relates to a P 1 ,P 4 - Process for the preparation of bis(uridine 5'-)tetraphosphate (UP4U) salt. Background technique [0002] Diquafosol tetrasodium also known as P 1 ,P 4 -Di(uridine 5′-)tetraphosphate, the structure shown in (Ia), is a second-generation uridine nucleotide analogue, which is a P2Y2 receptor agonist and mucin secretion stimulator, Japan Santen Pharmaceutical Co., Ltd. has developed 3% diquafosol tetrasodium eye drops for the treatment of dry eye. In addition, it has the possibility of further development as an expectorant having an effect of inducing expectoration or a drug for treating pneumonia. [0003] [0004] About P 1 ,P 4- Synthesis of di(uridine 5'-)tetraphosphate, Chinese patent CN101495497B discloses a dehydration condensation reaction of uridine 5'-triphosphate (UTP) to prepare uridine 5'-cyclic triphosphate, and then react with urine A method for preparing glycoside 5'-monophosphate (UMP) by ...

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): C07H19/10C07H1/04
CPCC07H19/10C07H1/04
Inventor 蔡洪芳陈埔范刘春樊波薛州洋
Owner JIANGSU HENGRUI MEDICINE 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