Unlock instant, AI-driven research and patent intelligence for your innovation.

Prodrug with nitrophenyl alkyl acid connected with alkaline antitumor drugs and preparation method thereof

A technology of nitrophenylalkanoic acid and anti-tumor drugs, which is applied in the field of anti-tumor prodrugs, can solve the problems of strong toxicity of anti-cancer drugs, complicated preparation process, high material cost, etc., and achieve improved anti-tumor efficacy and good anti-tumor Drug effect, strong anti-tumor drug effect

Active Publication Date: 2014-04-23
PEKING UNIV
View PDF2 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In order to solve the problems of strong toxicity and poor solubility of the above-mentioned anticancer drugs, various preparations of solubilized drugs are applied to the above-mentioned anticancer drugs, such as liposomes, micelles, solid dispersions, etc.
However, the preparation process of these methods is more complex and the cost of materials required is higher

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
  • Prodrug with nitrophenyl alkyl acid connected with alkaline antitumor drugs and preparation method thereof
  • Prodrug with nitrophenyl alkyl acid connected with alkaline antitumor drugs and preparation method thereof
  • Prodrug with nitrophenyl alkyl acid connected with alkaline antitumor drugs and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0026] Preparation of prodrugs linked with 2-nitrophenylacetic acid and paclitaxel

[0027] Weigh paclitaxel (94.05mg, 0.1101mmol), dicyclohexylcarbodiimide (28.49mg, 0.1321mmol), dimethylaminopyridine (26.85mg, 0.2188mmol), dissolve in 10ml distilled dichloromethane, stir , add 2-nitrophenylacetic acid (25.01mg, 0.1381mmol), and stir the reaction at room temperature for 24h. The material obtained from the above reaction was blown dry with nitrogen at room temperature or vacuum-dried under reduced pressure to obtain the crude prodrug.

[0028] Dissolve the obtained material in a small amount of dichloromethane and separate it by thin-layer analysis. After dissolving the obtained product band in ethyl acetate, filter it with suction. The filtrate is dried with nitrogen at room temperature or vacuum-dried under reduced pressure to obtain the pure product of the prodrug 110mg, the yield is 97.8%. The mass spectrum of the prodrug linked to 2-nitrophenylacetic acid and paclitaxel...

preparation example 2

[0031] Preparation of prodrugs linked to 2,2-dimethyl-(2-nitrophenyl)acetic acid and paclitaxel

[0032]Weigh paclitaxel (63.44mg, 0.074mmol), dicyclohexylcarbodiimide (17.98mg, 0.0873mmol), dimethylaminopyridine (18.16mg, 0.148mmol), dissolve in 10ml distilled dichloromethane, nitrogen protection Under stirring at 40°C, 2,2-dimethyl(2-nitrophenyl)acetic acid (18.56mg, 0.0889mmol) was added and refluxed for 120h. The material obtained from the above reaction was blown dry with nitrogen at room temperature or vacuum-dried under reduced pressure to obtain the crude prodrug.

[0033] Dissolve the obtained material in a small amount of dichloromethane and separate it by thin-layer analysis. After dissolving the obtained product band in ethyl acetate, filter it with suction. The filtrate is dried with nitrogen at room temperature or vacuum-dried under reduced pressure to obtain the pure product of the prodrug 70.0mg, the yield is 90.5%. The mass spectrum of the prodrug linked to ...

preparation example 3

[0036] Preparation of 3-(2-nitrophenyl)propionic acid-linked prodrugs of paclitaxel

[0037] Weigh paclitaxel (117mg, 0.1370mmol), dicyclohexylcarbodiimide (34.08mg, 0.1652mmol), dimethylaminopyridine (33.4mg, 0.2722mmol), dissolve in 10ml distilled dichloromethane, stir, Add 3-(2-nitrophenyl)propionic acid (32.01mg, 0.1640mmol), and stir the reaction at room temperature for 24h. The material obtained from the above reaction was blown dry with nitrogen at room temperature or vacuum-dried under reduced pressure to obtain the crude prodrug.

[0038] Dissolve the obtained material in a small amount of dichloromethane and separate it by thin-layer analysis. After dissolving the obtained product band in ethyl acetate, filter it with suction. The filtrate is dried with nitrogen at room temperature or vacuum-dried under reduced pressure to obtain the pure product of the prodrug 140mg, the yield is 99.2%. The mass spectrum of the prodrug of 3-(2-nitrophenyl)propanoic acid linked to ...

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 belongs to the field of molecule targeting system, and particularly relates to a prodrug with nitrophenyl alkyl acid compounds connected with alkaline antitumor drugs. The prodrug of the invention is characterized in that when compared with antitumor drugs, the prodrug enhances the in-vivo stability of antitumor drugs, reduces the toxicity of antitumor drugs to normal tissue, and also has the effect of targeting tumor tissue. The prodrug of the invention has better antitumor activity. The invention also relates to a preparation method and applications of the prodrug. The prodrug of the invention has better in-vivo and in-vitro stability, better effect of targeting tumor hypoxic tissue, and better antitumor effect.

Description

technical field [0001] The invention relates to an antitumor compound in the field of molecular targeting, in particular to an antitumor prodrug in which a nitrophenylalkanoic acid compound is linked with an antitumor drug. Background of the invention [0002] Nitrophenyl alkanes acid belongs to nitroalkanes. This type of compound has certain selectivity for tumor hypoxic tissue or intratumoral specific reductase. Specifically selected pharmaceutical intermediates can be used as target molecules for tumor targeting agents or drugs. [0003] Such compounds are small molecule organic acids, examples include but are not limited to 2-nitrophenylacetic acid, 2,2-dimethyl-(2-nitrophenyl)acetic acid, 3-(2-nitrophenyl ) Propionic acid (2-Nitrophenylacetic acid, 2,2-Dimethyl-(2-nitrophenyl) acetic acid, 3-(2-nitrophenyl) propionic acid), the molecular weights are 181.15, 209, 195.17, all light yellow to yellow crystals . The prodrugs obtained after linking this type of compound wi...

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): A61K47/48A61K31/337A61K31/704C07D305/14C07H15/252C07H1/00C07F15/00A61P35/00A61P35/02
Inventor 张烜宋平张强
Owner PEKING UNIV