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

4-phenylsulfonyl-1-trihydroxybenzoylpiperazine-2-carboxamide derivative and its preparation method and application

A kind of technology of trihydroxybenzoylpiperazine and phenylsulfonyl, applied in the field of derivatives and preparation thereof

Active Publication Date: 2022-06-17
SHANDONG UNIV
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] In order to discover a new generation of HIV inhibitors, the present invention discloses a class of HIV-1 RNase H inhibitors with a novel structure of 4-phenylsulfonyl-1-trihydroxybenzoylpiperazine-2-carboxamide derivatives. There is no relevant report in the technology

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
  • 4-phenylsulfonyl-1-trihydroxybenzoylpiperazine-2-carboxamide derivative and its preparation method and application
  • 4-phenylsulfonyl-1-trihydroxybenzoylpiperazine-2-carboxamide derivative and its preparation method and application
  • 4-phenylsulfonyl-1-trihydroxybenzoylpiperazine-2-carboxamide derivative and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1: Intermediate 1-(tert-butyl)3-methyl 4-(3,4,5-tri(benzyloxy)benzoyl)piperazine-1,3-dicarboxylate (IA- b) Preparation

[0043] Weigh 3,4,5-tribenzyloxybenzoic acid (2.0180g, 4.52mmol) into a 250mL flask, add 50mL N,N-dimethylformamide to dissolve, add 1-(3- Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.9322 g, 4.89 mmol), 1-hydroxybenzotriazole (0.6425 g, 4.97 mmol), triethylamine (1.25 mL, 10.06 mmol) ), stirred for 15 min, removed the ice bath, and stirred at room temperature for 1 h. Finally, 1-Boc-3-methylpiperazine-1,3-dicarboxylate or 1-Boc-2-methylpiperazine-1,2-dicarboxylate (1.0925 g, 5.51 mmol) was added to the flask ) and reacted overnight. After the reaction was completed, 150 mL of water was added to the reaction solution, resulting in white turbidity. After mixing, it was transferred to a separatory funnel, extracted with ethyl acetate (3×50 mL), and the organic phases were combined, followed by 1N hydrochloric acid solution and sat...

Embodiment 2

[0044] Example 2: Preparation of intermediate 1-(3,4,5-tris(benzyloxy)benzoyl)piperazine-2-carboxylic acid methyl ester (IA-c)

[0045] IA-b (1.2305 g, 2.51 mmol) was weighed and dissolved in 5 mL of dichloromethane, then trifluoroacetic acid (2.12 mL, 30 mmol) was slowly added thereto, and the mixture was stirred at room temperature for 6 h. TLC detected the completion of the reaction, added 10 mL of water to the reaction solution, adjusted the pH to 9 with saturated sodium bicarbonate solution, extracted three times with dichloromethane, washed 2-3 times with saturated sodium chloride solution, combined the organic layers, anhydrous sodium sulfate dry. Then through flash column chromatography, recrystallization from ethyl acetate-petroleum ether system gave a pale yellow solid, yield: 81%, mp: 156-158°C. 1 H NMR (400MHz, DMSO-d 6 )δ7.42(t,J=6.7Hz,6H),7.35(dd,J=7.1,1.1Hz,3H),7.39–7.25(m,6H),6.95(s,2H),5.16(s,6H ), 4.78(t, J=5.2Hz, 1H), 4.03(m, 6H), 3.67(s, 3H), 1.08(s, 1H,...

Embodiment 3

[0046] Example 3: Intermediate 4-((4-nitrophenyl)sulfonyl)-1-(3,4,5-tris(benzyloxy)benzoyl)piperazine-2-carboxylic acid methyl ester ( Preparation of IA-d-1)

[0047] Weigh the intermediate IA-c (1.5012g, 0.18mmol) and add it to a 50mL flask, add 20mL of dichloromethane to dissolve, and add triethylamine (0.75mL, 0.36mmol) and p-nitrogen to the reaction flask in turn under ice bath conditions benzenesulfonyl chloride (0.9212 g, 0.27 mmol), removed the ice bath after 30 min, and stirred at room temperature for 12 h. TLC detected the completion of the reaction, concentrated the reaction solution, extracted three times with ethyl acetate, combined the organic phases, washed with 1N hydrochloric acid solution and saturated sodium bicarbonate solution for 2-3 times in turn, and finally washed with saturated sodium chloride solution for 1-2 times Second-rate. The organic phase was transferred to a 250 mL conical flask, an appropriate amount of anhydrous sodium sulfate was added, d...

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 present invention provides a 4-phenylsulfonyl-1-trihydroxybenzoylpiperazine-2-carboxamide derivative, which has the structure shown in the following general formula IA or IB. The invention also relates to a preparation method of the derivative and its application as an HIV inhibitor in the preparation of anti-AIDS drugs.

Description

technical field [0001] The invention relates to a derivative and a preparation method thereof, in particular to the preparation of a 4-phenylsulfonyl-1-trihydroxybenzoylpiperazine-2-carboxamide derivative and its application in the field of anti-HIV medicines, belonging to The technical field of organic synthesis and medical application. Background technique [0002] AIDS is short for Acquired immunodeficiency syndrome (AIDS), which is mainly caused by infection with human immunodeficiency virus 1 (HIV-1). HIV attacks CD4, the most important part of the body's immune system + T lymphocytes make the human body lose its immune function, resulting in a variety of infections, and complications such as malignant tumors often occur in the later stage, eventually leading to systemic failure and death. The popularization of "Highly Active Antiretroviral Therapy" (HAART) has brought good news to AIDS patients. Through the combined use of three or more anti-HIV-1 drugs targeting dif...

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 Patents(China)
IPC IPC(8): C07D241/04C07D405/12C07D409/12C07D487/10A61K31/495A61K31/496A61P31/18
CPCC07D241/04C07D405/12C07D409/12C07D487/10A61P31/18Y02P20/55
Inventor 展鹏魏粉菊刘新泳张丽娜李雅信吕冬雪王颖
Owner SHANDONG 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