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

Novel coronavirus main protease inhibitor and preparation method and application thereof

An unsaturated and selected technology, used in antiviral agents, medical preparations containing active ingredients, pharmaceutical formulations, etc., can solve the problems of limited efficacy, toxic and side effects, and achieve pathological damage improvement, reduction in quantity, and good pharmacokinetics. Effects of Dynamic Properties

Active Publication Date: 2022-02-18
SICHUAN UNIV
View PDF1 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] For coronavirus pneumonia (COVID-19, also known as novel coronavirus pneumonia) caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2, also known as novel coronavirus), alpha-interferon has been used clinically and the anti-HIV drug lopinavir / ritonavir combination, but the efficacy is still very limited and there may be toxic side effects

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
  • Novel coronavirus main protease inhibitor and preparation method and application thereof
  • Novel coronavirus main protease inhibitor and preparation method and application thereof
  • Novel coronavirus main protease inhibitor and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0080] Embodiment 1: the preparation of compound 1

[0081]

[0082] Compound 1 of the present invention is obtained according to the above-mentioned preparation route, and the reaction conditions of each step in the route are as follows:

[0083] i, a, dimethyl 2-fluoromalonate, benzyl alcohol, toluene, p-toluenesulfonic acid, 110°C; b, isopropanol, n-hexane, -10°C;

[0084] ii. Isopropanol, sodium hydroxide, water, 45°C;

[0085] iii. Anhydrous tetrahydrofuran, isopropylmagnesium chloride tetrahydrofuran solution, Ar, 0°C;

[0086] iv. Anhydrous tetrahydrofuran, N,N'-carbonyldiimidazole, Ar, 0°C;

[0087] v, ethyl acetate, 10% palladium carbon, hydrogen, room temperature;

[0088] vi, dichloromethane, dioxane hydrochloride solution;

[0089] vii. Dichloromethane, N,N,N',N'-tetramethyl-O-(7-azabenzotriazol-1-yl)urea hexafluorophosphate, N,N-diisopropyl ethyl Amine, -20°C;

[0090] viii, dichloromethane, trifluoroacetic acid;

[0091] ix, dichloromethane, N,N,N',N'-t...

Embodiment 2

[0111] Embodiment 2: the preparation of compound 3

[0112]

[0113] Compound 3 of the present invention is obtained according to the above-mentioned preparation route, and the reaction conditions of each step in the route are as follows:

[0114] i. Boc-L-dimethyl glutamate, LiHMDS tetrahydrofuran solution, argon, anhydrous tetrahydrofuran, -78°C;

[0115] ii. (2S,4R)-dimethyl 2-(tert-butoxycarbonylamino)-4-(cyanomethyl) glutarate, anhydrous methanol, cobalt chloride hexahydrate, sodium borohydride;

[0116] iii. (S)-methyl 2-(tert-butoxycarbonylamino)-3-((S)-2-carbonylpyrrolidin-3-yl)propionate, lithium hydroxide monohydrate, tetrahydrofuran, 0 ℃;

[0117] iv. Anhydrous tetrahydrofuran, Ar, N,N'-carbonyldiimidazole, 0°C;

[0118] v, ethyl acetate, 10% palladium carbon, hydrogen, room temperature;

[0119] vi, dichloromethane, dioxane hydrochloride solution;

[0120] vii. Dichloromethane, N,N,N',N'-tetramethyl-O-(7-azabenzotriazol-1-yl)urea hexafluorophosphate, N,N-di...

Embodiment 3

[0142] Embodiment 3: preparation compound 9

[0143]

[0144] Compound 9 of the present invention is obtained according to the above-mentioned preparation route, and the reaction conditions of each step in the route are as follows:

[0145] i. 1-hydroxybenzotriazole, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N,N-diisopropylethylamine, N,N-di Methylformamide, room temperature.

[0146] ii. Sodium hydroxide, methanol, water, 55 degrees

[0147] iii. 2-(7-benzotriazole oxide)-N,N,N',N'-tetramethyluronium hexafluorophosphate, N,N-diisopropylethylamine, N,N-di Methylformamide, 0°C

[0148] iv. Sodium borohydride, methanol, room temperature

[0149] v. Dess Martin oxidant, ultra-dry dichloromethane, room temperature

[0150] The following are the specific synthesis steps:

[0151] Intermediate 25: Methyl(1R,2S,5S)-6,6-Dimethyl 3-(quinoline-2-carbonyl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid preparation

[0152] Starting material 23 (quinoline 2-carb...

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 provides a novel coronavirus main protease inhibitor as well as a preparation method and application thereof. Specifically provided is a compound represented by formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or an optical isomer thereof, or an isotope substitution form thereof. The compound can be used for effectively inhibiting the activity of SARS-CoV-2 Mpro, and can be used for preparing an SARS-CoV-2 Mpro inhibitor to block the replication and transcription of SARS-CoV-2 virus in the body of a patient. The compound disclosed by the invention has a very good application prospect in the preparation of an SARS-CoV-2 Mpro inhibitor, an SARS-CoV-2 resisting medicine and a medicine for preventing and / or treating novel coronavirus pneumonia.

Description

technical field [0001] The invention belongs to the technical field of organic synthetic medicines, and in particular relates to an inhibitor of novel coronavirus main protease, a preparation method thereof and a pharmaceutical use thereof. Background technique [0002] For coronavirus pneumonia (COVID-19, also known as novel coronavirus pneumonia) caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2, also known as novel coronavirus), alpha-interferon has been used clinically and the anti-HIV drug lopinavir / ritonavir combination, but the efficacy is still very limited, and there may be toxic side effects. Remdesivir, a broad-spectrum antiviral drug developed by Gilead Sciences, Inc., is also being explored as a treatment for COVID-19, but more data is needed to prove its efficacy. Therefore, there is still an urgent need to develop safe and effective anti-SARS-CoV-2 drugs. [0003] The genome RNA of coronavirus is about 30knt long, has a 5' cap stru...

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): C07D403/14C07D471/04C07D209/52C07D401/06C07D403/12C07D401/14C07D401/12C07D405/14A61P31/14A61K31/403A61K31/4439A61K31/4725A61K31/437A61K31/4709A61K31/4184
CPCC07D403/14C07D471/04C07D209/52C07D401/06C07D403/12C07D401/14C07D401/12C07D405/14A61P31/14
Inventor 杨胜勇李琳丽
Owner SICHUAN UNIV
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