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

Tricyclene compounds with HIV antagonistic activity and preparation method and application thereof

A compound and solvent compound technology, which is applied in the field of tricycloalkene compounds, can solve problems such as rapid mutation of HIV virus

Inactive Publication Date: 2010-07-14
INST OF BIOENG ACAD OF MILITARY MEDICAL SCI OF THE CHINESE
View PDF1 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0016] Due to the rapid mutation of HIV virus, the current clinical anti-HIV drugs show certain drug resistance to different patients and in different treatment processes

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
  • Tricyclene compounds with HIV antagonistic activity and preparation method and application thereof
  • Tricyclene compounds with HIV antagonistic activity and preparation method and application thereof
  • Tricyclene compounds with HIV antagonistic activity and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] Compound 1: N-(3,3a,4,4a,5,5a,6,6a decahydro-1,3-dioxo-4,6-vinylidenecyclopropane[f]isoindole-2(1H )-yl)-4-(2-methylpiperazine-1-methyl)benzamide

[0057] Step 1: Methyl p-Bromomethylbenzoate

[0058] To a solution of methyl p-toluate (3.07g, 20mmol) in carbon tetrachloride (30ml), add N-bromosuccinimide (4.14g, 23mmol), and heat to reflux for 6h. Then the reaction solution was cooled, filtered, and washed three times with carbon tetrachloride (each 10ml), and the filtrate was collected and spin-dried to obtain yellow oily methyl p-bromomethylbenzoate (4.22g, yield 90%). Purification is required, and the next reaction can be carried out directly.

[0059] Step 2: Methyl 4-((4-methylpiperazin-1-yl)methyl)benzoate

[0060] To a solution of methyl p-bromomethylbenzoate (4.22g, 18mmol) and DIEA (5ml, 29mmol) in dichloromethane (35ml) was added dropwise with stirring 2.22ml (20mmol) of N-methylpiperazine. After the dropwise addition was completed, the reaction was carrie...

Embodiment 2

[0069] Compound 2: N-(3,3a,4,4a,5,5a,6,6a decahydro-1,3-dioxo-4,6-vinylidenecyclopropane[f]isoindole-2(1H )-yl)-4-((1 hydrogen-benzimidazol-1-yl)methyl)benzamide

[0070] The synthesis method is basically the same as that of compound 1, except that N-methylpiperazine in step 2) of the example is replaced with benzimidazole. Yield 60%, mp: 272-274°C.

[0071] The structural confirmation data are as follows:

[0072] 1 H NMR (400Hz, d 6 -DMSO): δ11.05 (s, 1H, CONH), 8.42 (s, H, imidazol-2-H), 7.85 (m, 2H, Ar-H), 7.67 (m, 1H, Ar-H), 7.42(m, 3H, Ar-H), 7.20(m, 2H, Ar-H), 5.78(s, 2H, CH=CH), 5.60(s, 2H, Ar-CH 2 ), 3.32(m, 4H, 2×COCH, 2× CH -CH=CH), 1.07(s, 2H, 2× CH -CH 2 ), 0.26 (m, 2H, CH 2 ).

[0073] MS (FAB, Glycerin) m / z calculated value C 26 h 22 N 4 o 3 (M+1): 439.5, measured value: 439.2 (M+1).

Embodiment 3

[0075] Compound 3: N-(3,3a,4,4a,5,5a,6,6a decahydro-1,3-dioxo-4,6-vinylidenecyclopropane[f]isoindole-2(1H )-yl)-4-((2-methyl-1 hydrogen-benzimidazol-1-yl)methyl)benzamide

[0076] The synthesis method is basically the same as that of compound 1, except that the N-methylpiperazine in step 2) of the example is replaced by 2-methylbenzimidazole. Yield 74%, mp: 261-262°C.

[0077] The structural confirmation data are as follows:

[0078] 1 H NMR (400Hz, CDCl 3 ): δ10.62(s, 1H, CONH), 7.88(d, J=8.0Hz, 2H, Ar-H), 7.68(d, J=7.6Hz, 1H, Ar-H), 7.23(m, 3H , Ar-H), 6.94 (d, J=7.6Hz, 2H, Ar-H), 5.68 (s, 2H, CH=CH), 5.35 (s, 2H, Ar-CH 2 ), 3.43(s, 2H, 2×COCH), 3.12(s, 2H, 2× CH -CH=CH), 2.35(s, 3H, CH 3 ), 1.11 (d, J=4.4Hz, 2H, 2× CH-CH 2 ), 0.28 (m, 2H, CH 2 ).

[0079] MS(Turbo Spray)m / z calcd for C 27 h 24 N 4 o 3 Calculated: 453.5, Measured: 453.1.

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 tricyclene compounds with HIV antagonistic activity and a preparation method and application thereof. A structural formula of the tricyclene compounds is shown as a formula I, wherein R is alkyl, a naphthenic group, heteroaryl, substituted alkyl, substituted phenyl or substituted heteroaryl; and a substituting group of the substituted alkyl is any one of an alkoxyl group, a substituted or unsubstituted phenoxy group, a naphthenic group, heteroaryl, a substituted naphthenic group, substituted heteroaryl and substituted amido. An in-vitro HIV-1 infected cell model tests the activity and shows that the compounds are superactive HIV antagonists, can be used as inhibitors for inhibiting replication of HIV virus, and can be developed into anti-AIDS medicaments.

Description

technical field [0001] The invention relates to a tricycloalkene compound with HIV antagonistic activity, a preparation method and application thereof. Background technique [0002] AIDS epidemic [0003] According to data forecast released by the United Nations Program on HIV / AIDS (UNAIDS) in May 2006, by the end of 2008, there were estimated to be 33.2 million HIV-infected and AIDS patients in the world. In 2008 there were 2.7 million new infections and 2 million deaths. Since the discovery of AIDS, the cumulative number of people who have died of AIDS in the world has reached 25 million. AIDS has become the fourth leading cause of death after heart disease, stroke and acute lower respiratory tract infection in the world, and it is the infectious disease that causes the most deaths in the world. According to the "Joint Assessment Report on AIDS Prevention and Control in China (2007)" published by the Ministry of Health, as of the end of October 2007, a total of 223,501 ...

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): C07D403/12C07D209/70C07D401/14A61K31/496A61K31/4184A61K31/403A61K31/4196A61K31/4439A61P31/18
Inventor 戴秋云董铭心彭旭清
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