3S-indole methyl-6R-aromatic amino acid modified piperazine-2,5-dione, synthesis, activities and applications thereof

A technology of n-hexanoylamino, -d-trp-obzl, applied in the field of biomedicine, can solve the problems of no anti-tumor metastasis effect and unsatisfactory clinical curative effect of tumor chemotherapy

Inactive Publication Date: 2018-12-11
CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Because the existing anti-tumor drugs have no anti-tumor metastasis effect, the clinical efficacy of tumor chemotherapy is not ideal

Method used

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  • 3S-indole methyl-6R-aromatic amino acid modified piperazine-2,5-dione, synthesis, activities and applications thereof
  • 3S-indole methyl-6R-aromatic amino acid modified piperazine-2,5-dione, synthesis, activities and applications thereof
  • 3S-indole methyl-6R-aromatic amino acid modified piperazine-2,5-dione, synthesis, activities and applications thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Example 1 Preparation of Boc-Lys(Cbz)-D-Trp-OBzl

[0020] Suspend 4.56g (10mmol) L-Boc-Lys (Cbz) in 100mL of anhydrous tetrahydrofuran (THF), and add 1.35g (10mmol) 1-hydroxybenzotriazole ( HOBt) and 2.47g (12mmol) of dicyclohexylcarbodiimide (DCC), then stirred for 30min. Afterwards, 3.31 g (10 mmol) of D-Trp-OBzl were added. The reaction compound was added dropwise to N-methylmorpholine (NMM) to adjust the pH to 9. The reaction mixture was first stirred under ice bath for 1 h, and then stirred at room temperature for 12 h. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure, and the residue was dissolved in 150 mL of ethyl acetate solution. The obtained ethyl acetate solution was sequentially washed with 5% KHSO 4 Wash 3 times with aqueous solution and 3 times with saturated NaCl aqueous solution. Ethyl acetate layer with anhydrous Na 2 SO 4 Dry for 12h, filter, and concentrate the filtrate to dryness under reduced pressure. ...

Embodiment 2

[0021] Example 2 Preparation of Lys(Cbz)-D-Trp-OBzl

[0022] 3.28 g (5 mmol) Boc-Lys(Cbz)-D-Trp-OBzl was slowly mixed with 52 mL of hydrogen chloride in ethyl acetate under stirring in an ice bath. The resulting solution was stirred for 5 h in an ice bath. After that, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in 50 mL of anhydrous ethyl acetate, and the resulting solution was concentrated under reduced pressure. This operation was repeated three times. The residue was washed well with anhydrous ether to obtain 2.36 g (85%) of the title compound as a colorless powder. ESI-MS(m / e):557[M+H] + .

Embodiment 3

[0023] Example 3 Preparation of (3S,6R)-3-(benzyloxycarbonylamino-n-butyl)-6-(indole-3-methyl)-piperazine-2,5-dione (1)

[0024] Dissolve 2.22 g (4 mmol) of L-Lys(Cbz)-D-Trp-OBzl in 100 ml of ethyl acetate, adjust the pH to 9 with triethylamine, and stir at 80° C. for 100 hours. A colorless solid was filtered off. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (CH 2 Cl 2 / CH 3 OH, 100 / 1). A total of 1.32 g (65%) of the title compound was obtained. ESI-MS(m / e):449[M+H] + .

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Abstract

The invention relates to 3S-indole methyl-6R-aromatic amino acid modified piperazine-2,5-dione, synthesis, activities and applications thereof, and discloses (3S,6R)-3-(AA-amino-hexanoylamino-n-butyl)-6-(indole-3-methyl)-piperazine-2,5-dione represented by the following formula (AA is L-Phe residue and L-Tyr residue), a preparation method, anti-tumor activity, anti-tumor-metastasis activity and anti-inflammatory activity thereof, such that the present invention discloses applications of the (3S,6R)-3-(AA-amino-hexanoylamino-n-butyl)-6-(indole-3-methyl)-piperazine-2,5-dione in preparation of anti-tumor drugs, anti-tumor-metastasis drugs and anti-inflammatory drugs. The formula is defined in the specification.

Description

technical field [0001] The present invention relates to (3S,6R)-3-(AA-aminocaproylamino-n-butyl)-6-(indole-3-methyl)-piperazine-2,5-dione. Related to their preparation method, related to their anti-tumor activity, related to their anti-tumor metastasis activity, and related to their anti-inflammatory activity, thus the present invention relates to their use in the preparation of anti-tumor drugs, anti-tumor transfer drugs and anti-inflammatory drugs Applications. The invention belongs to the field of biomedicine. Background technique [0002] Tumors seriously threaten human health. In addition to the poor prognosis of cancer patients, the concurrent metastasis of tumors further worsens the prognosis of patients. For example, more than 90% of cancer patients died of metastasis. Because the existing anti-tumor drugs have no anti-tumor metastasis effect, the clinical curative effect of tumor chemotherapy is unsatisfactory. It is an urgent clinical need to invent drugs agai...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D403/06A61P35/04A61P35/00A61P29/00
CPCC07D403/06
Inventor 赵明彭师奇吴建辉王玉记胡西胡明芳
Owner CAPITAL UNIVERSITY OF MEDICAL SCIENCES
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