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

Polypeptide compound, preparation, medicine composition, preparation method and application

A technology of compounds and polypeptides, applied in the field of medicine, can solve the problem of not easy tolerance, and achieve the effects of less side effects, good analgesic activity, and low brain permeability

Inactive Publication Date: 2020-02-14
CHENGDU SINTANOVO BIOTECHNOLOGV CO LTD
View PDF1 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, the body is not prone to tolerance to kappa opioid receptor agonists

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
  • Polypeptide compound, preparation, medicine composition, preparation method and application
  • Polypeptide compound, preparation, medicine composition, preparation method and application
  • Polypeptide compound, preparation, medicine composition, preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Preparation of Polypeptide Compound TM-1

[0066] Step 31: Int-1 (0.545 g, 0.622 mmol), HOBT (0.201 g, 1.492 mmol), HBTU (0.566 g, 1.492 mmol), and DIEA (0.320 g, 2.488 mmol) were dissolved in DCM (15 mL) at room temperature Under stirring for 0.5h, then add the crude product of Int-4 and react at room temperature for 2h. The reaction solution was washed with saturated ammonium chloride solution, water and saturated brine respectively, dried over anhydrous sodium sulfate, and the crude product after filtration and concentration was purified by Prep-HPLC to obtain intermediate compound 1-1;

[0067] Step 32: Add TFA (1 mL) dropwise to a solution of 1-1 (500 mg) in DCM (2 mL), stir at room temperature for 1 h, and purify the crude product after concentration to dryness by Prep-HPLC to obtain the trifluoropolypeptide compound TM-1 acetate.

[0068] The mass spectrometry and NMR characterization of the prepared TM-1 are as follows:

[0069] ESI-MS(m / z):665.4(M+H + )

...

Embodiment 2

[0081] Preparation of polypeptide compound TM-2

[0082] This embodiment is based on embodiment 1, and the difference with embodiment 1 is:

[0083] The dosage of Int-1 is 0.093g; Int-4 is replaced by pyrrole-3-boronic acid pinacol ester; the synthesis of pyrrole-3-boronic acid pinacol ester is similar to Int-4, by N-tert-butoxycarbonyl-pyrrole -3-Boronic acid pinacol ester is obtained by removing the protecting group under acidic conditions. The obtained crude product was purified by Prep-HPLC to obtain 13.3 mg of the trifluoroacetate salt of the target compound TM-2.

[0084] The mass spectrometry and NMR characterization of the prepared TM-2 are as follows:

[0085] ESI-MS(m / z):651.4(M+H + )

[0086] 1H NMR (400MHz, DMSO): δ8.76-8.73(m,1H),8.38–8.16(m,2H),8.02(s,3H),7.70(s,3H),7.39–7.13(m,10H) ,4.69-4.64(m,1H),4.52-4.43(m,2H),4.02(s,1H),3.44–3.25(m,3H), 3.14-3.02(m,3H),2.96-2.90(m, 1H),2.87–2.66(m,3H),2.01-1.92(m,1H),1.71–1.29(m,11H), 0.92-0.87(m,6H).

Embodiment 3

[0088] Preparation of peptide compound TM-3:

[0089] This embodiment is based on embodiment 1, and the difference with embodiment 1 is:

[0090] The dosage of Int-1 is 0.090g, replace Int-4 with 2,5-dihydro-1H-pyrrole-3-boronic acid pinacol ester; 2,5-dihydro-1H-pyrrole-3-boronic acid pinacol ester The synthesis of the ester is similar to that of Int-4, which can be obtained by deprotecting N-tert-butoxycarbonyl-2,5-dihydro-1H-pyrrole-3-boronic acid pinacol ester under acidic conditions. The obtained crude product was purified by Prep-HPLC to obtain 13.3 mg of the trifluoroacetate salt of the target compound TM-3.

[0091] The mass spectrometry and NMR characterization of the prepared TM-3 are as follows:

[0092] ESI-MS(m / z):649.4(M+H + )

[0093] 1H NMR (400MHz, CD 3 OD):δ7.44–7.12(m,10H),6.58–6.34(m,1H),4.77–4.52(m,3H), 4.48-4.25(m,4H),4.11-4.06(m,1H), 3.28–3.18(m,1H),3.06–2.89(m,4H),1.88-1.80(m,1H), 1.79–1.38(m,8H),1.02–0.91(m,6H).

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 a polypeptide compound, a preparation, a medicine composition, a preparation method and application. The polypeptide compound has a structural formula as shown in a general formula (I). The polypeptide compound used as a k opioid receptor stimulant has the advantages of better activity, less side effects and better druggability.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a polypeptide compound, preparation, pharmaceutical composition, preparation method and application. Background technique [0002] Analgesics mainly act on the central or peripheral nervous system, selectively inhibit and relieve various pains, and relieve pain caused by fear, tension and anxiety pain. The current global pain relief market is dominated by opioids and NSAIDs, which together accounted for more than 52% of the total market revenue in 2015. According to a report by Transparency Market Research, the global pain relief market will reach $88.2 billion by the end of 2025. [0003] Opioid receptors are a major class of G protein-coupled receptors and are binding targets for endogenous opioid peptides as well as opioids. Opioid receptor activation can regulate the immune system and endocrine system of the nervous system, and is currently the most powerful and commonly used centra...

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): C07K5/107A61K38/07A61P29/00A61P17/04A61P7/10A61P3/12A61P1/00A61P11/14A61P27/06
CPCC07K5/1016A61P29/00A61P17/04A61P7/10A61P3/12A61P1/00A61P11/14A61P27/06A61K38/00Y02P20/55C07K5/0202
Inventor 高剑付晓平钟国庆李四军周海波胡海胡西李元波
Owner CHENGDU SINTANOVO BIOTECHNOLOGV 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