Thymosin alpha 1 active segment cyclicpeptide analogue and its poly glycol derivative

A technology of peptide derivatives and compounds, applied in the field of related diseases, can solve the problems of long cycle, large dosage and high price

Inactive Publication Date: 2006-06-07
INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Currently, Tα1 (Zidaxian) in clinical use is a chemical synthetic product, which is expensive, has a large dosage, and a long cycle. Therefore, the research on the structure-activity relationship finds that better analogues have better application prospects.

Method used

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  • Thymosin alpha 1 active segment cyclicpeptide analogue and its poly glycol derivative
  • Thymosin alpha 1 active segment cyclicpeptide analogue and its poly glycol derivative
  • Thymosin alpha 1 active segment cyclicpeptide analogue and its poly glycol derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0550] wxya 2 CH 2 OCH 2 Synthesis of COOH: BocNHCH 2 OCH 2 COOH

[0551]

[0552] ●BocNHCH 2 CH 2 Synthesis of OH

[0553] Add 30ml of water into the 250ml reactor, NH 2 CH 2 CH 2 OH6.1g (100mmol) was added into the reactor and cooled to 0°C. Under ice bath conditions, (Boc) 2 O2 1.82g (100mmol) was dissolved in 30ml of dioxane and added to the reactor, the temperature was controlled below 0°C, 100ml of 1mol / L NaOH solution was added dropwise, and after 40min, the dropwise addition was completed, and it was naturally raised to room temperature, and the reaction was continued for 12 hours. (Boc) 2 O disappears, the reaction is stopped, and the plate is detected. The reaction solution is extracted three times with ethyl acetate, washed with saturated NaCl solution, and washed with anhydrous NaCl solution. 2 SO 4 After drying and evaporating to dryness under reduced pressure, 15.6 g of a colorless oil was obtained with a yield of 97.2%.

[0554] ●BocNHCH 2...

Embodiment 2

[0557] Cys-Glu-Val-Val-Glu-SCH 2 CH 2 CONH 2 Synthesis:

[0558] 350mg MBHA resin (loading capacity: 0.57mmol / g, 0.2mmol), suspended in DMF, sequentially add 0.12gHOBt, 150μL 3-mercaptopropionic acid (1.2mmol), 160mg DCC, add a small amount of DCM to dissolve fully, and magnetically Stir for 4 hours, wash twice with DMF, DCM, MeOH, and DCM, each for two minutes. Ninhydrin test was negative. Then mix and dissolve DMF with 50mg cysteine ​​methyl ester hydrochloride (0.2mmol), 100mg (0.2mmol) triphenylphosphine and 120 μ IDIEA (0.2mmol), add in the resin after five minutes, react at room temperature for two hours, use DMF, DCM, MeOH, and DCM were washed twice each, mixed with 4 times the amount of BOC-protected amino acids, BOP, and 6 times the amount of DIEA, dissolved in DMF, and the mixture was added to the reactor after five minutes, and reacted at room temperature for 2 hours. Wash with DMF, DCM, MeOH, DCM, and use qualitative Ellman test to detect. Negative solution re...

Embodiment 3

[0559] Embodiment three: the synthesis of ring (CEVVE):

[0560] 350mg MBHA resin (loading capacity: 0.57mmol / g, 0.2mmol), suspended in DMF, sequentially add 0.12gHOBt, 150μL 3-mercaptopropionic acid (1.2mmol), 160mg DCC, add a small amount of DCM to dissolve fully, and magnetically Stir for 4 hours, wash twice with DMF, DCM, MeOH, and DCM, each for two minutes. Ninhydrin test was negative. Then mix and dissolve DMF with 50mg cysteine ​​methyl ester hydrochloride (0.2mmol), 100mg (0.2mmol) triphenylphosphine and 120μl DIEA (0.2mmol), add in the resin after five minutes, react at room temperature for two hours, use DMF, DCM, MeOH, and DCM were washed twice each, mixed with 4 times the amount of BOC-protected amino acids, BOP, and 6 times the amount of DIEA, dissolved in DMF, and the mixture was added to the reactor after five minutes, and reacted at room temperature for 2 hours. Wash with DMF, DCM, MeOH, DCM, and use qualitative Ellman test to detect. Negative solution resin ...

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PUM

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Abstract

The present invention relates to a kind of cyclopeptide derivative containing natural or artificial amino acid substituted active thymosin alpha-1 segemnt, and its preparation process, medicine composition and their medicines for treating or preventing diseases related to immune deficiency, hypoimmunity, etc.

Description

field of invention [0001] The present invention relates to natural or non-natural amino acid substituted thymosin α1 active fragments and cyclic peptide analogs, and their PEGylated derivatives, and their preparation methods, pharmaceutical compositions containing them and their therapeutic or prophylaxis and immunodeficiency , low immune function and other related diseases. Background technique [0002] Thymosin α1 (Tα1) is an important polypeptide immune regulatory factor, which has a significant effect of enhancing immune function. It is an immune enhancer for T lymphocytes, which can promote the maturation and differentiation of T cells, and promote the mature Lymphocytes secrete a variety of lymphokines (such as interleukin-2 and γ-interferon, etc.) and can also promote the production of interleukin-2 receptors. Tα1 consists of 28 amino acid residues, with a molecular weight of 3108, an isoelectric point of 4.2, and an acetylated structure at the N-terminal. Its amino ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K5/10A23L33/18A61K38/07A61K38/08A61P37/02A61P37/04C07K7/06
Inventor 刘克良蒋志龙王良友梁远军许笑宇吴萍韩寒
Owner INST OF PHARMACOLOGY & TOXICOLOGY ACAD OF MILITARY MEDICAL SCI P L A
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