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A kind of multi-target anticancer drug and its preparation method and application

An anti-cancer drug, multi-target technology, applied in the field of medicine, can solve problems such as disorder and apoptosis disorder, and achieve the effect of strong binding affinity and obvious non-peptide characteristics

Active Publication Date: 2019-10-29
GUANGDONG UNIV OF TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the past few decades, despite some advances in cancer therapy, tumor cell resistance to various cytotoxic stimuli, apoptosis disorder and dysregulation are still the main obstacles that cancer therapy has to overcome.

Method used

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  • A kind of multi-target anticancer drug and its preparation method and application
  • A kind of multi-target anticancer drug and its preparation method and application
  • A kind of multi-target anticancer drug and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Embodiment 1 (multi-target anticancer drug G 1 )

[0050] The synthesis method of compound A (the structural formula of compound A is shown in formula II) refers to the preparation method in paragraphs [0046] to [0083] of Chinese patent 201610036840.2.

[0051] (S)-2-((5R,8S,10aR)-5-(tert-butoxycarboxamido)-6-carbonylthiazepine[1,5]pyrrolidine[2,1-d]- Preparation of 8-carboxamido)-3-phenylpropionic acid methyl ester (compound B):

[0052]

[0053] At -10°C, L-phenylalanine methyl ester hydrochloride (62mg, 0.29mmol), EDCI (572mg, 2.9mmol), HOBt (392mg, 2.9mmol) were added to compound A (99mg, 0.29mmol) Dry the dichloromethane (10 mL) solution, and then add DIEA to adjust the pH of the reaction solution to alkaline. The mixture was stirred overnight at room temperature, then diluted with dichloromethane, and washed successively with dilute hydrochloric acid solution, saturated sodium carbonate solution, and saturated brine. The organic phase was dried over anhydro...

Embodiment 2

[0066] Embodiment 2 (multi-target anticancer drug G 2 )

[0067] The synthesis method of compound A (the structural formula of compound A is shown in formula VI) refers to the preparation method in paragraphs [0046] to [0083] of Chinese patent 201610036840.2.

[0068] (R)-2-((5R,8S,10aR)-5-(tert-butoxycarboxamido)-6-carbonylthiazepine[1,5]pyrrolidine[2,1-d]- 8-Carboxamido)-3-phenylpropanoic acid methyl ester (Compound B)

[0069]

[0070] At 0°C, D-phenylalanine methyl ester hydrochloride (188mg, 0.87mmol), DCC (1196mg, 5.8mmol), HOOBt (946mg, 5.8mmol) were added to the dry solution of compound A (99mg, 0.29mmol) dichloromethane solution (15 mL), and then added triethylamine to adjust the pH of the reaction solution to alkaline. The mixture was stirred overnight at room temperature, then diluted with dichloromethane, and washed successively with saturated ammonium chloride solution, saturated sodium bicarbonate solution, and saturated brine. The organic phase was dried ...

Embodiment 3

[0082] Embodiment 3 (compound G 3 )

[0083] The synthesis method of compound A refers to the preparation method in paragraphs [0046] to [0083] of Chinese patent 201610036840.2.

[0084] (S)-2-((5R,8S,10aR)-5-(tert-butoxycarboxamido)-6-carbonylthiazepine[1,5]pyrrolidine[2,1-d]- Preparation of 8-carboxamido)-3-phenylpropionic acid methyl ester (compound B):

[0085]

[0086] At 15°C, L-phenylalanine methyl ester hydrochloride (313mg, 1.45mmol), BOP (128mg, 0.29mmol), HOSu (8mg, 0.07mmol) were added to the dry solution of compound A (99mg, 0.29mmol) Chloroform solution (5 mL), and then add pyridine to adjust the pH of the reaction solution to alkaline. The mixture was stirred overnight at room temperature, then diluted with chloroform, and washed successively with dilute hydrochloric acid solution, saturated sodium bicarbonate solution, and saturated brine. The organic phase was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. Th...

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Abstract

The invention discloses a multiple-target-point anti-cancer drug, a preparation method and an application thereof and belongs to the technical field of drugs. The multiple -target-point anti-cancer drug has a structural formula as shown in formula I, wherein X is selected from-O-or-OCH2O-substituent group and R3 is selected from-CN or -ONO2 -. The multiple-target-point anti-cancer drug designed and compounded according to the invention has strong binding affinity with XIAP-BIR3, can effectively accelerate cancer cell apoptosis, has more obvious non-peptide characteristics, can act on multiple target points and has multiple effects.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a multi-target anticancer drug and its preparation method and application. Background technique [0002] In recent years, in order to make drugs act on multiple targets, multi-target drugs that combine two pharmacophores into one drug molecule have become a new hot spot in the development of new drugs. Due to the complexity of many serious diseases such as cancer and neurodegenerative diseases, these diseases are difficult to be cured by a highly selective pharmacophore, which is why multi-target drugs have received special attention in recent years. Compared with ordinary drugs, multi-target drugs can be used to improve molecular affinity and selectivity, reduce side effects, etc. The constituent units of multi-target drug molecules can be artificially designed or natural organic small molecules, polypeptides, nucleic acids, etc. For the target, these pharmacophor...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K5/078A61K38/05A61P35/00
CPCA61K38/00C07K5/06139
Inventor 董长治盛钊君张焜史一鸣杜志云
Owner GUANGDONG UNIV OF TECH