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

Endomorphin analog and its preparing method

An endomorphin and analog technology, applied in the field of new compounds and their preparation methods and pharmacological efficacy, can solve the problems of limited application of analgesics, dose dependence, limited application, etc. Pain-specific effect

Inactive Publication Date: 2006-01-04
LANZHOU UNIVERSITY
View PDF0 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] However, due to the flexible molecular structure of endomorphins, they can have different conformations required for molecular recognition of various receptors, including binding to different subtypes of receptors, so that their selectivity is low, and some side effects occur in clinical treatment. For example, endomorphin can significantly reduce the systemic arterial pressure and heart rate of experimental animals in a dose-dependent manner to experimental animals such as rabbits, cats, mice, and rats, thus limiting its application as an analgesic
At the same time, as an opioid, endomorphin also has the inherent weakness of opioids. If it has a certain degree of addiction, it also increases difficulties for clinical use.
Moreover, endomorphin also has the weaknesses of peptide drug molecules, such as easy metabolism, poor resistance to enzymolysis, short half-life of action, etc., which limit its application.

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
  • Endomorphin analog and its preparing method
  • Endomorphin analog and its preparing method
  • Endomorphin analog and its preparing method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Embodiment 1: compound c (Tyr-D-Pro-Phe-Gly-NHCH (CH 3 ) Ph, the synthesis of tyrosyl-D type-prolylphenylalanylglycyl-L-α-methylbenzylamine)

[0041] Compound i (Z-Gly, N-benzyloxycarbonylglycine) was dissolved in anhydrous DCM (adding anhydrous DMF to aid dissolution), ice bathed, and 1.5 times the amount of L-(-)α-methylbenzylamine was added, and then Ice-bathed for 10 minutes, then added 1.5 times the amount of DCC dissolved in pre-cooled dichloromethane (DCM), stirred in the ice bath for 30 minutes, added 0.5 times the amount of DMAP, after 30 minutes, returned to room temperature and reacted for 40 hours, filtered off DCU, The filtrate was concentrated under reduced pressure to remove the solvent, dissolved in ethyl acetate, and then washed with dilute hydrochloric acid, saturated NaHCO 3 , NaCl solution, and dried over anhydrous sodium sulfate. The crude product was recrystallized with EA / PE (1:2, V / V) to obtain compound ii (Z-Gly-NHCH(CH 3 )Ph): yield = 86.7%;...

Embodiment 2

[0048] Embodiment 2: compound a (Tyr-Pro-Phe-Gly-NHCH (CH 3 ) Ph, the synthesis of tyrosylprolylphenylalanylglycyl-L-α-methylbenzylamine)

[0049] Compound viii (Phe-Gly-NHCH(CH 3 ) Ph) structure and synthesis process are the same as in Example 1.

[0050] Dissolve equimolar amounts of Z-Tyr and HOSu in anhydrous THF, slowly drop into the pre-cooled THF solution in which an equivalent amount of DCC was dissolved, and react overnight at room temperature under cooling at 3 After the solution was dissolved, it was added dropwise into the Z-Tyr-OSu solution, and reacted at room temperature for about 2 days. After the reaction was finished, 6 mol / L HCl was slowly added dropwise until the pH of the solution was 2. It was then concentrated under reduced pressure to remove THF, extracted with ethyl acetate, washed with acid, then washed with NaCl solution until neutral, and dried by adding anhydrous sodium sulfate. Anhydrous sodium sulfate was filtered off, and concentrated under r...

Embodiment 3

[0053] Embodiment 3: compound d (Tyr-D-Pro-Phe-Ala-NHCH (CH 3 ) Ph, the synthesis of tyrosyl-D type-prolylphenylalanylalanyl-L-α-methylbenzylamine)

[0054] See Example 1 for the synthesis of compound vii (Z-Tyr-D-Pro) in Example 3; compound xii (Phe-Ala-NHCH(CH 3 )Ph) synthetic process and concrete operation and embodiment 1 compound viii (Phe-Gly-NHCH(CH 3 ) Ph) is similar, except that the raw material compound i (Z-Gly) in Example 1 is changed to compound xiii (Z-Ala, N-benzyloxycarbonylalanine) to react to obtain xii (Phe-Ala-NHCH( CH 3 )Ph).

[0055] Dissolve equimolar amounts of compound vii (Z-Tyr-D-Pro) and HOBt in anhydrous DCM / DMF mixed solvent, and slowly drop into the pre-cooled DCM solution in which equimolar amounts of DCC were dissolved under ice-salt bath cooling and stirring , After reacting at room temperature for 12h, filter off DCU to obtain Z-Tyr-D-Pro-OBt solution. Ice-salt bath, stirring, adding 1.2 times the amount of compound xii (Phe-Ala-NHCH(CH ...

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

PropertyMeasurementUnit
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
Login to View More

Abstract

The four kinds of endomorphin analogs with analgetic effect with the shown structures are prepared with Z-Tyr-Pro-OH or Z-Tyr-D-Pro-OH as I segment and Z-Phe-Ala-NHCH (CH3)Ph or Z-Phe-Gly-NHCH(CH3)Ph as the II segment and through segment condensation process. The preparation process has minimum protection on amino acid; DCC / DMAP synthesis of material Z- Ala-NHCH (CH3) Ph and Z- Gly-NHCH(CH3)Ph; DCC / HOSu synthesis of segments and DCC / HOBt synthesis between segments with DCC / HOBt coupling agent; crystal separating purification of intermediate product; and common silicon gel column chromatography for purifying final product. Serial experiments show that these endomorphin analogs are polypeptide precursor with excellent analgetic activity and may be further developed into analgetic polypeptide medicine for research and clinical application.

Description

technical field [0001] The present invention relates to a class of novel compounds and their preparation methods and pharmacological effects, in particular to a class of endomorphin-2 analogues and their preparation methods and analgesic activity, and are applied in the pharmaceutical and chemical industries. Background technique [0002] Endomorphins (EMs) are divided into endomorphin-1 (endomorphin-1, EM-1, Tyr-Pro-Trp-Phe-NH 2 ) and endomorphin-2 (endomorphin-2, EM-2, Tyr-Pro-Phe-Phe-NH 2 ), which is an endogenous agonist of mu-opioid receptor (MOR), has a very high affinity and selectivity for MOR, and has a wide range of physiological and pharmacological effects, especially potent analgesic effects. [0003] The amino acid composition and structure of endomorphin are shown in the following formula: [0004] [0005] EM-1: Tyr-Pro-Trp-Phe-NH 2 EM-2: Tyr-Pro-Phe-Phe-NH 2 [0006] As bioactive peptides with potent analgesic ef...

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): C07K5/10C07K1/22A61P25/04
Inventor 王锐张启军
Owner LANZHOU UNIVERSITY
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