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

Prodrug based on cytosine arabinoside structure, and synthesis method and application thereof

A kind of technology of cytarabine and synthetic method, applied in the application field of prodrug and drug based on cytarabine structure

Inactive Publication Date: 2011-07-06
SANLUGEN PHARMATECH
View PDF5 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, Metabasis work is limited to cytosine O 5 ring phosphorylation

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 based on cytosine arabinoside structure, and synthesis method and application thereof
  • Prodrug based on cytosine arabinoside structure, and synthesis method and application thereof
  • Prodrug based on cytosine arabinoside structure, and synthesis method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0063] The present invention also provides the synthesis method of the prodrug based on the cytarabine structure, comprising the following steps:

[0064] 1) Acid anhydride or acid chloride and alcohol are directly mixed or dissolved in an organic solvent according to the ratio of acid anhydride or acid chloride: alcohol = 1: 1 to 1: 1.5 molar ratio, and reacted at room temperature to the melting temperature of the reactant for 2 to 8 hours to obtain the corresponding The substituted acid (ie R in the above formula 1 COOH);

[0065] 2) Cytarabine hydrochloride, the substituted acid obtained in step 1), benzotriazole-1-oxytripyrrolidinylphosphonium hexafluorophosphate (PyBOP) and 4-dimethylaminopyridine (DMAP) according to 1: (1~2): (0.9~1.5): (1~3) ratio of molar ratio dissolved in organic solvent, stirring at room temperature for 12~24 hours;

[0066] 3) Pour the reaction solution in step 2) into water, extract, and dry and purify the separated organic phase to obtain the t...

specific Embodiment approach

[0097] Hereinafter, the present invention will be described more specifically using examples, but the present invention is not limited to the following examples.

[0098] Cytarabine, purchased from Suzhou Surui Pharmaceutical Chemical Co., Ltd.;

[0099] Benzotriazole-1-oxytripyrrolidinylphosphine hexafluorophosphate was purchased from Jill Biochemical (Shanghai) Co., Ltd.;

[0100] 4-Dimethylaminopyridine was purchased from Jill Biochemical (Shanghai) Co., Ltd.

Embodiment 1

[0102] N 4 -(5-n-dodecyloxyformylthiophene-2-formyl)-cytarabine (compound NO.1)

[0103] 1.0 g of 2,5-thiophenedicarboxylic acid (5.8 mmol) was added to 15 mL of 8OCl 2 Add 2 drops of DMF and heat to reflux for 4 hours. spin off SOCl 2 , 1.21 g of thiophene-2,5-diacyl chloride was obtained almost quantitatively.

[0104] Dissolve 1.21g of thiophene-2,5-diacyl chloride (5.8mmol) in 30mL of dioxane, add 1.01g of lauryl alcohol and 2mL of Et 3 N 5mL dioxane solution, reacted for 4h, concentrated to dryness, the residue was dissolved in water, adjusted to pH 2-3, extracted three times with ethyl acetate, and the separated organic phase was dried with anhydrous sodium sulfate. After evaporation of the solvent under reduced pressure, 5-n-dodecyloxyformylthiophene-2-carboxylic acid was obtained almost quantitatively.

[0105] 406mg of cytarabine (1.67mmol), 683mg of 5-n-dodecyloxyformylthiophene-2-carboxylic acid (2.01mmol), 955mg of benzotriazole-1-oxytripyrrolidinylphosphonium...

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 nucleoside drugs, and relates to a prodrug based on a cytosine arabinoside structure as disclosed in Formula (I) and a synthesis method and application thereof. In the Formula (I), A is a heterocyclic compound or a heterocyclic compound with a substituent group in the ring; the connecting position in the ring can be any chemically-allowed position; a is a whole number of 0-6, b is a whole number of 0-6, and c is a C6-C18 alkoxy group, such as C10H21O, C12H25O, C18H37O, C2H5OC12H25O and the like; and R2 is H or a group with the structure disclosed as the following Formula (II), wherein W1 is H or a C3-C18 alkyl group, and W2 is H or a C3-C18 alkyl group. The solubility, bioavailability and organ specificity of the prodrug are enhanced through the N4-site modification; and the generated prodrug compound can solve the problem of high metabolism speed, improve the antitumor, anticancer, anti-infection and anti-proliferation capacities, and specifically act on the liver or colon. The synthesis method provided by the invention has the advantages of simple steps, accessible raw materials, high yield and low cost, and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the field of nucleoside drugs, and relates to a prodrug based on the structure of cytarabine, a synthesis method thereof, and the application of the prodrug based on the structure of cytarabine for treating various cancers and related diseases. Background technique [0002] According to WHO statistics, in 2007, there were as many as 12 million newly diagnosed cancer patients in the world, and over the past few years, more than 7 million patients worldwide died of cancer every year. This figure is very close to the number of people who die from acute cardiovascular disease. Cancer is about to become the deadliest disease in the world. [0003] Nucleoside drugs, such as cytarabine, gemcitabine, decitabine, azacitidine, cladribine, fludarabine, clofibrate, nelarabine, 6-azauridine and thiazofurin, etc. It is widely used in the treatment of various cancers. At the same time, many nucleoside drugs are in the clinical research sta...

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
IPC IPC(8): C07H19/09C07H19/10C07H1/00A61K31/7068A61P35/00A61P31/00
CPCC07H19/10A61K31/7068C07H19/09A61P31/00A61P35/00
Inventor 薛晓霞李刚王荣周孙昌俊李文保
Owner SANLUGEN PHARMATECH
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