Check patentability & draft patents in minutes with Patsnap Eureka AI!

Fluorine-19 modified nitroimidazole compound and preparation method and application of derivative thereof

A technology for nitroimidazole and compound is applied in the field of preparation of nitroimidazole compound and derivatives thereof, can solve the problems of low utilization rate of fluorine signal fluorine atom, poor water solubility, etc. The effect of convenience and convenience for storage and transportation

Active Publication Date: 2022-05-13
INNOVATION ACAD FOR PRECISION MEASUREMENT SCI & TECH CAS
View PDF6 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among them, CCI-103F is a commercial hypoxia probe (HypoxyprobeTM-F6). Because of its poor water solubility, it needs to be dissolved in 10% DMSO / peanut oil and used by intraperitoneal injection; SR4554 has entered phase I clinical research, but The five fluorine-19 contained in the structure are not magnetically equivalent, and there are problems of fluorine signal splitting and low utilization of fluorine atoms

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
  • Fluorine-19 modified nitroimidazole compound and preparation method and application of derivative thereof
  • Fluorine-19 modified nitroimidazole compound and preparation method and application of derivative thereof
  • Fluorine-19 modified nitroimidazole compound and preparation method and application of derivative thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] 1. Synthesis of 1-propynyl-2-nitroimidazole

[0047] Weigh 2-nitroimidazole (6.0g, 53.1mmol) and anhydrous potassium carbonate (8.8g, 63.7mmol) into a 500mL round-bottomed flask, then add 100mL N,N-dimethylformazol to the round-bottomed flask Amide (DMF) was dissolved, and then the toluene solution (7.5mL) of 3-bromopropyne (7.6g, 5.5mL, 63.7mmol) was slowly added to the round bottom flask. After the addition was completed, the round bottom flask was placed in Under 60 ℃ and carry out stirring reaction, TLC traces the reaction process, after the 2-nitroimidazole reaction is complete, stop heating, add 100mL water to quench in the round bottom flask, then the obtained mixed product is extracted with ethyl acetate, and with A separatory funnel was used to separate the organic phase, and the resulting organic phase was evaporated to remove the solvent, and the resulting residue was purified through a silica gel column (200-300 mesh) to obtain a brownish-yellow liquid (7.1 ...

Embodiment 2

[0069] Under nitrogen protection, sodium hydride (0.6mg, 0.015mmol, 60%, dispersed in mineral oil) was suspended in anhydrous tetrahydrofuran (1mL), and then fluorine-19 modified nitroimidazole compound (5.0mg, 0.010 mmol) in anhydrous tetrahydrofuran (1 mL), and stirred at room temperature for half an hour, then added tetraethylene glycol cyclic sulfate (4.0 mg, 0.015 mmol) in anhydrous tetrahydrofuran (1 mL) to obtain a reaction mixture, The resulting reaction mixture was stirred and reacted at room temperature. After the reaction, water (0.4mL, 0.020mmol) was added, and the pH of the system was adjusted to 3.0 with concentrated sulfuric acid, and the reaction was continued to stir at room temperature. After the reaction was completed, saturated carbonic acid was added. The sodium hydrogen aqueous solution was neutralized, and then the solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel thin-layer chromatography preparative plate...

Embodiment 3

[0072] Under nitrogen protection, sodium hydride (0.6mg, 0.015mmol, 60%, dispersed in mineral oil) was suspended in anhydrous tetrahydrofuran (1mL), and then fluorine-19 modified nitroimidazole compound (5.0mg, 0.010 mmol) in anhydrous tetrahydrofuran (1 mL), and stirred at room temperature for half an hour, then added 1,3-propane sultone (1.9 mg, 0.015 mmol) in anhydrous tetrahydrofuran (1 mL) to obtain a reaction mixture , the resulting reaction mixture was stirred and reacted at room temperature. After the reaction was completed, methanol was added to quench the reaction, and then the obtained mixed product was evaporated to remove the solvent, and the obtained residue was purified by preparative plate of silica gel thin layer chromatography to obtain The following compounds:

[0073]

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 discloses a fluorine-19 modified nitroimidazole compound and a preparation method and application of a derivative of the fluorine-19 modified nitroimidazole compound, the nitroimidazole compound is composed of three parts, the first part is a hypoxic targeting group 2-nitroimidazole which has responsiveness to a tumor hypoxic region; the second part is a fluorine signal source perfluoro-tert-butyl alcohol fragment, and the perfluoro-tert-butyl alcohol fragment contains 9 symmetrical fluorine-19 and can generate a single fluorine signal, so that the problems of fluorine signal splitting and low fluorine atom utilization rate are avoided, and the imaging concentration of the compound is reduced; the third part is a triazole ring which is connected with a 2-nitroimidazole fragment and a fluorine signal fragment through triazole, so that the water solubility of the triazole ring is improved. Therefore, the nitroimidazole compound has targeting property on a tumor hypoxia region, has better water solubility, can generate a single and high-intensity fluorine signal, and is suitable for preparing a < 19 > F MRI (Magnetic Resonance Imaging) contrast agent for tumor hypoxia detection.

Description

technical field [0001] The invention belongs to the technical field of tumor hypoxia detection and analysis, and specifically relates to a preparation method and application of a fluorine-19 modified nitroimidazole compound and a derivative thereof. Background technique [0002] Hypoxia is a ubiquitous pathophysiological feature in solid tumors. Due to the rapid growth of solid tumors, the oxygen supply capacity of the blood vessels is insufficient, and its abnormal vascular morphology will cause poor blood flow, which will cause a decrease in the partial oxygen partial pressure and form a hypoxic area. Hypoxia is closely related to tumor invasion and metastasis, resistance to radiotherapy and chemotherapy, and prognosis. Therefore, detecting hypoxia in tumors has important clinical significance. [0003] Clinically, the oxygen electrode measurement method is currently the "gold standard" for detecting tumor hypoxia, but this method needs to insert a needle electrode into t...

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): C07D403/06A61K49/10
CPCC07D403/06A61K49/10C07B2200/05
Inventor 陈世桢李昱余巧刘昭清周欣
Owner INNOVATION ACAD FOR PRECISION MEASUREMENT SCI & TECH CAS
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com