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

Multi-arm pegylated aripiprazole derivative and preparation

A technology of aripiprazole and its derivatives, which is applied in the field of pharmaceutical synthesis, can solve problems such as limited loading capacity, and achieve the effects of increasing immobilization rate, increasing drug activity, and improving curative effect

Inactive Publication Date: 2018-11-30
湖南华腾制药有限公司
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Ordinary linear PEG has only two terminal modification groups, so when it is connected with small molecule drugs, the loading capacity is very limited, while multi-armed PEG has more than 2 modifiable terminals

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
  • Multi-arm pegylated aripiprazole derivative and preparation
  • Multi-arm pegylated aripiprazole derivative and preparation
  • Multi-arm pegylated aripiprazole derivative and preparation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] (1) Preparation of Intermediate II

[0025] Dissolve 10mmol of aripiprazole in 100ml of toluene, add 12mmol of adipic anhydride and 2mmol of DMAP at room temperature, and then stir at 90°C for 36h. After the reaction was completed, the solution was distilled off under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain intermediate II. Yield: 87.8%. NMR data are as follows: 1H(CDCl3):1.5-1.7(m,8H),2.25(m,4H), 2.3-2.5(m,8H),2.7(m,2H),3.3(m,2H),3.9( m,2H),6.4(m,2H),7.0(m,IH), 7.1(s,IH),7.3(m,2H)and 9.9(s,IH),

[0026] (2) Preparation of 4arm-PEG24-aripiprazole-IV

[0027] Dissolve 12mmol of intermediate II in 50ml of anhydrous chloroform, add 20mmol of oxalyl chloride, add 1mmol% of DMF as a catalyst, and stir the reaction at 25°C for 10h. The solvent and excess acid chloride were evaporated under reduced pressure, 50ml of anhydrous chloroform was added to the reaction system, and 2mmol of 4arm-PEG24-NH2 was a...

Embodiment 2

[0029] (1) Preparation of Intermediate II

[0030] Dissolve 10mmol of aripiprazole in 100ml of toluene, add 12mmol of adipic anhydride and 3mmol of DMAP at room temperature, and then stir at 100°C for 24h. After the reaction was completed, the solution was distilled off under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain intermediate II. Yield: 82.8%. NMR data are as follows: 1H(CDCl3):1.5-1.7(m,8H),2.25(m,4H), 2.3-2.5(m,8H),2.7(m,2H),3.3(m,2H),3.9( m,2H),6.4(m,2H),7.0(m,IH), 7.1(s,IH),7.3(m,2H)and 9.9(s,IH),

[0031] (2) Preparation of 4arm-PEG124-aripiprazole-IV

[0032] Dissolve 12mmol of intermediate II in 50ml of anhydrous chloroform, add 30mmol of oxalyl chloride, add 2mmol% of DMF as a catalyst, and stir the reaction at 25°C for 10h. The solvent and excess acid chloride were evaporated under reduced pressure, 50ml of anhydrous chloroform and 2mmol of 4arm-PEG24-NH2 were added to the reaction system, an...

Embodiment 3

[0034] (1) Preparation of Intermediate II

[0035] Dissolve 10 mmol of aripiprazole in 100 ml of toluene, add 14 mmol of adipic anhydride and 1 mmol of DMAP at room temperature, and then stir at 110° C. for 20 h. After the reaction was completed, the solution was distilled off under reduced pressure to obtain a crude product. The crude product was purified by column chromatography to obtain intermediate II. Yield: 89.9%. NMR data are as follows: 1H(CDCl3):1.5-1.7(m,8H),2.25(m,4H), 2.3-2.5(m,8H),2.7(m,2H),3.3(m,2H),3.9( m,2H),6.4(m,2H),7.0(m,IH), 7.1(s,IH),7.3(m,2H)and 9.9(s,IH),

[0036] (2) Preparation of 4arm-PEG240-aripiprazole-IV

[0037] Dissolve 15mmol of intermediate II in 50ml of tetrahydrofuran, add 25mmol of oxalyl chloride, add 5mmol% of DMF as a catalyst, and stir the reaction at 25°C for 10h. The solvent and excess acid chloride were evaporated under reduced pressure, 50ml of anhydrous chloroform and 2mmol of 4arm-PEG240-NH2 were added to the reaction system, a...

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 utilizes the characteristics of nontoxicity and easiness of binding of multi-arm PEG (polyethylene glycol), combines four-arm PEG, six-arm PEG and eight-arm PEG with the aripiprazole. The prodrug of the multi-arm loaded aripiprazole has good water solubility, more importantly, a multi-arm PEG chain is connected with a plurality of residues of aripiprazole, the loading rate of the drug is greatly improved, the half-life period of the drug is greatly prolonged, the existing time of the drug in the blood is greatly prolonged, so that the curative effect is improved.

Description

technical field [0001] The present invention relates to the field of pharmaceutical synthesis, in particular to a multi-armed PEGylated aripiprazole derivative and its preparation method and its application in the preparation of antipsychotic drugs. Background technique [0002] Aripiprazole (aripiprazole) is a commonly used antipsychotic drug in clinical practice. As a second-generation atypical antipsychotic drug, it is a derivative of quinolinones. The third generation of antipsychotic drugs, the reason is that aripiprazole not only blocks dopamine (DA) receptors in the brain, but also stabilizes the serotonin (5-HT) system. When aripiprazole is used for the treatment of schizophrenia, it has unique pharmacological properties and significant clinical curative effect. Both positive symptoms and negative symptoms are significantly improved, and the incidence of adverse reactions of aripiprazole is low, thus improving the Patient adherence to medication. With the increasin...

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): A61K47/60A61K31/496A61P25/18C08G65/333
CPCA61K47/60A61K31/496A61P25/18C08G65/33396
Inventor 张安林邓泽平成佳
Owner 湖南华腾制药有限公司
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