Cetrorelix synthesis method

A technology for cetrelix and receptide, applied in the field of synthesizing cetrelix, can solve the problems such as the inability to improve the total yield, and achieve the effect of high purity and high total yield

Active Publication Date: 2018-03-09
CHENGDU SHENGNUO BIOPHARM
View PDF8 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, on the one hand, it uses toxic hydrazine hydrate to remove the D-Orn (Dde) side chain protecting group Dde; on the other hand, the traditional trifluoroacetic acid lysis solution cannot comple...

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
  • Cetrorelix synthesis method
  • Cetrorelix synthesis method
  • Cetrorelix synthesis method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Embodiment 1: the synthesis of D-Ala-MOBHA resin

[0050] Take 0.15mol Fmoc-D-Ala and 0.15mol HOBt, and dissolve them with an appropriate amount of DMF; take another 0.15mol DIC, and slowly add it to the DMF solution of the protected amino acid under stirring, and stir and react at room temperature for 30 minutes to obtain the activated protected amino acid. Amino acid solution, spare.

[0051] Take 0.05mol of MOBHA resin (substitution value about 0.6mmol / g), swell with DMF for 25 minutes, wash and filter, add activated Fmoc-D-Ala solution, stir at room temperature for 3 hours, remove the reaction solution, and wash with DMF for 3 times Finally, DCM was washed 3 times, and the washing time was 3 minutes each time to obtain Fmoc-D-Ala-MOBHA resin, which was deprotected with 20% PIP / DMF solution for 25 minutes, washed and filtered to obtain D-Ala-MOBHA resin.

Embodiment 2

[0052] Embodiment 2: the synthesis of D-Ala-MOBHA resin

[0053] Take 0.15mol Boc-D-Ala and 0.15mol HOBt, and dissolve them with appropriate amount of DMF; take another 0.15mol DIC, slowly add it into the DMF solution of the protected amino acid under stirring, and stir and react at room temperature for 30 minutes to obtain the activated protected amino acid. Amino acid solution, spare.

[0054] Take 0.05mol of MOBHA resin (substitution value about 0.6mmol / g), swell with DMF for 25 minutes, wash and filter, add activated Fmoc-D-Ala solution, stir at room temperature for 3 hours, remove the reaction solution, and wash with DMF for 3 times Finally, wash with DCM 3 times, each washing time is 3min, to obtain Boc-D-Ala-MOBHA resin, deprotect with 30% TFA / DCM solution for 30 minutes, neutralize with DIEA / DCM solution, wash and filter with DMF and DCM D-Ala-MOBHA resin was obtained.

Embodiment 3

[0055] Embodiment 3: the synthesis of Pro-D-Ala-MOBHA resin

[0056] Take 0.15mol Fmoc-Pro and 0.15mol HOBt, and dissolve them with an appropriate amount of DMF; take another 0.15mol DIC, slowly add it to the protected amino acid DMF solution under stirring, and stir and react at room temperature for 30 minutes to obtain the activated protected amino acid solution .

[0057] Add the above-mentioned activated protected amino acid solution to the D-Ala-MOBHA resin prepared in Example 1, stir and react at room temperature for 3 hours, remove the reaction solution, wash 3 times with DMF, and wash 3 times with DCM, each washing time is After 3 minutes, deprotect with 20% PIP / DMF solution for 25 minutes, wash and filter to obtain Pro-D-Ala-MOBHA resin.

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 relates to the field of synthesis of medicines and discloses a cetrorelix synthesis method. A brand new amino resin is used as a carrier, protected D-Orn is taken as a precursor of D-Cit, a side chain protecting group is removed, the D-Orn is reacted with tert-butyl isocyanate to generate the D-Cit (tBu), a cetrorelix resin is dissolved by a special trifluoroacetic acid solution comprising hydrogen bromide, moreover, the side chain protecting group tBu of the generated D-Cit (tBu) is maximally removed, the finally obtained cetrorelix is higher in purity and total yield, the production of the toxic impurity [D-Cit(Ac)]-cetrorelix is avoided, the whole method is simple, convenient and easy to operate, the conditions are mild, and the product quality is relatively high.

Description

technical field [0001] The invention relates to the field of pharmaceutical synthesis, in particular to a method for synthesizing cetrorelix. Background technique [0002] Cetrorelix is ​​a gonadotropin-releasing hormone (GnRH) antagonist. GnRH binds to receptors on the pituitary cell membrane to stimulate the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Cetrorelix competes with endogenous GnRH for receptors on pituitary cells, thereby inhibiting the release of endogenous LH and FSH. The inhibitory effect of cetrorelix occurs immediately after injection and there is no stimulatory effect. In women, cetrorelix works by delaying the onset of the LH surge, thereby controlling ovulation. The effect of cetrorelix is ​​dose-dependent, 3 mg of cetrorelix can maintain the drug effect for 4 days, and the inhibitory effect on the 4th day is about 70%. Injection of cetrorelix 0.25 mg every 24 hours can make the inhibitory effect sustained. Animal exp...

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): C07K7/23C07K1/06C07K1/04
CPCC07K7/23Y02P20/55
Inventor 马中刚郭德文曾德志文永均
Owner CHENGDU SHENGNUO BIOPHARM
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