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

1-(3-aminopropyl) piperazine-4-aminoamide compound as well as preparation method and application thereof

A compound, the technology of piperidinecarboxamide, which is applied to 1-(3-aminopropyl)piperazine-4-aminoamide compounds and the fields of preparation and application thereof, can solve drug resistance, high toxicity of antiviral drugs, etc. question

Inactive Publication Date: 2012-01-18
INST OF BIOENG ACAD OF MILITARY MEDICAL SCI OF THE CHINESE +1
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, HIV-1 has developed resistance to almost all current antiviral drugs, and antiviral drugs generally have disadvantages such as high toxicity

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
  • 1-(3-aminopropyl) piperazine-4-aminoamide compound as well as preparation method and application thereof
  • 1-(3-aminopropyl) piperazine-4-aminoamide compound as well as preparation method and application thereof
  • 1-(3-aminopropyl) piperazine-4-aminoamide compound as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1, 1-acetyl-N-[3-(4-benzylpiperazin-1-yl)propyl]-N-(3-chloro-4-methylphenyl)piperidine-4-methyl Synthesis of amides (DMX-B01) (in formula I, X is methylene, R 1 for phenyl compounds)

[0049] 1. Preparation of N-(3-chloropropyl)-3-chloro-4-methylaniline

[0050] To a solution of 3-chloro-4-methylaniline (7.08 g, 50 mmol) in DMF (5 mL) was added 1-bromo-3-chloropropane (15.5 mL, 50 mmol), potassium iodide (0.83 g, 5 mmol) and triethyl Amine (30 mL). The mixture was stirred at room temperature for 3 days. Then the solvent was evaporated to dryness, diluted with diethyl ether (100 mL) and washed with brine, the separated organic phase was dried over sodium sulfate and concentrated under reduced pressure. The concentrate was separated by column chromatography (ethyl acetate / petroleum ether=1:25, v / v), and the light brown oil was obtained as N-(3-chloropropyl)-3-chloro-4-methylaniline (10 g, yield 92%).

[0051] The structural confirmation data are as follows: ...

Embodiment 2

[0072] Example 2, 1-acetyl-N-[3-(4-benzoylpiperazin-1-yl)propyl]-N-(3-chloro-4-methylphenyl)piperidine-4- Synthesis of formamide (DMX-B02) (in formula I, X is a carbonyl group, R1 is a phenyl compound)

[0073] According to the method for preparing the target compound DMX-B01 in Example 1, by 1-acetyl-N-(3-chloro-4-methylphenyl)-N-(3-chloropropyl)-4-piperidinecarboxamide (0.37g, 1.0mmol) was reacted with 1-benzoylpiperazine trifluoroacetate (0.45g, 1.5mmol) (provided by Amber Technology Co., Ltd.) to obtain 0.2g of yellow foamy solid, with a yield of 38%.

[0074] The structural confirmation data are as follows:

[0075] 1 H NMR (400Hz, CDCl 3 ): δ7.31(m, 6H), 7.17(m, 1H), 6.97(d, J=6.4Hz, 1H), 4.52(d, J=13.6Hz, 1H), 3.74(m, 3H), 3.51 (m, 2H), 2.47(m, 4H), 2.42(s, 3H), 2.34(m, 6H), 2.04(s, 3H), 1.70(m, 6H);

[0076] MS (Turbo Spray) m / z (M+1): 525.6.

Embodiment 3

[0077] Example 3, 1-acetyl-N-{3-[1-(2-chloro-thiazol-5-yl-methylene)piperazin-1-yl]propyl}-N-(3-chloro- Synthesis of 4-methylphenyl)piperidine-4-formamide (DMX-B03) (in formula I, X is methylene, R 1 is 5-2-chloro-thiazolyl compound)

[0078] According to the above-mentioned method for preparing the target compound DMXB01, from 1-acetyl-N-(3-chloro-4-methylphenyl)-N-(3-chloropropyl)-4-piperidinecarboxamide (0.37g, 1.0mmol) was reacted with 1-(2-chloro-thiazol-5-yl-methyl)piperazine dihydrochloride (0.26g, 0.9mmol) (provided by Amber Technology Co., Ltd.) to obtain 0.35g yellow foamy solid, Yield 70%.

[0079] The structural confirmation data are as follows:

[0080] 1 H NMR (400Hz, CDCl 3 ): δ7.34(m, 2H), 7.18(s, 1H), 6.98(d, J=1.72Hz, 1H), 4.52(d, J=13.4Hz, 1H), 3.77(d, J=13.7Hz , 3H), 3.65(m, 4H), 2.85(m, 1H), 2.47(m, 3H), 2.42(s, 3H), 2.34(m, 6H), 2.05(s, 3H), 1.66(m, 6H);

[0081] MS (Turbo Spray) m / z (M+1): 554.5.

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 1-(3-aminopropyl) piperazine-4-aminoamide compound as well as a preparation method and application thereof. The structural general formula of the compound is shown as a formula I, wherein R1 is the following groups unsubstituted or substituted by 1-3 substituents: phenyl groups, benzyl groups, naphthyl groups, C5-C10 aromatic heterocyclic groups or C4-C7 saturated heterocyclic groups; the heterocyclic groups comprises 1-3 (at least 1) heteroatoms selected from N, O and S; the substituents are selected from the following atoms or groups: halogen, sulfydryl groups, hydroxyl groups, CF3, CN, NO2 and SO2CH3; and X is methylene, carbonyl or does exist. Through cell activity screening of an HIV-1 infected Bal(R5) lymphoid tissue sample, the series of compound is found to have very strong anti-HIV (Human Immunodeficiency Virus) activity, wherein the compound with strongest activity has the IC50 value reaching 10nM and the selection index more than 14.545 and can be developed into anti-AIDs medicaments. The formula I is shown in the specification.

Description

technical field [0001] The invention relates to 1-(3-aminopropyl)piperazine-4-aminoamide compounds, their preparation method and application. Background technique [0002] AIDS (AIDS) is a disease caused by human immunodeficiency virus (HIV) infection, mainly manifested by immune deficiency. Since the first case of AIDS was reported in the United States in 1981, AIDS has become the infectious disease that has caused the most deaths in the world. The advent of cocktail therapy has greatly reduced the mortality rate of HIV-1 infected persons. However, HIV-1 has developed drug resistance to almost all current antiviral drugs, and antiviral drugs generally have disadvantages such as high toxicity. Therefore, it is still an important task to discover and develop anti-HIV drugs with definite mechanism of action and novel structure types. [0003] The CCR5 receptor, a member of the chemokine receptor family, is an important co-receptor for HIV-1 to enter cells. In some people wh...

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): C07D211/62A61K31/496C07D417/12A61P31/18C07D401/12
Inventor 戴秋云董铭心姜世勃陆虹
Owner INST OF BIOENG ACAD OF MILITARY MEDICAL SCI OF THE CHINESE
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