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

N-hydroxyamide derivatives and use thereof

A kind of hydroxy amide, derivative technology, applied in N-hydroxy amide derivative and its application field

Inactive Publication Date: 2013-12-04
MERCK PATENT GMBH
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, a dose-limiting side effect of many MMPIs is musculoskeletal syndrome (tendinitis, fibrogenesis, mylasia, arthralasia)

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
  • N-hydroxyamide derivatives and use thereof
  • N-hydroxyamide derivatives and use thereof
  • N-hydroxyamide derivatives and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0842] Example 1: (2S,3S)-N,2-dihydroxy-5-methyl-3-{[4-(2-pyridyl)-1-piperazinyl]carbonyl}hexanamide (1)

[0843]

[0844] Step a) Formation of (5S)-2,2-dimethyl-5-((1S)-3-methyl-1-{[4-(2-pyridyl)-1-piperazinyl]carbonyl}butyl base)-1,3-dioxolan-4-one

[0845]

[0846] To (2S)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-4-methylpentanoic acid pentafluorophenyl ester and ( 2R)-2-[(4S)-2,2-Dimethyl-5-oxo-1,3-dioxolan-4-yl]-4-methylpentanoic acid pentafluorophenyl ester (intermediate 1 ; 792.6mg; 2.0mmol; 1.0eq) of the 55 / 45 diastereoisomer mixture in DMF (15mL) was added 1-(2-pyridyl)piperazine (326.5mg; 2.0mmol; 1.0eq ). After 14 hours at room temperature, the solvent was evaporated to an oil. Chromatography (SiO 2 ) to afford the title compound as a colorless oil (50 / 50 mixture of 2 diastereoisomers). This product was dissolved in iPrOH (10 mL) and kept at -20°C for 48 hours. The supernatant was collected and evaporated to a colorless oil (301 mg, 40%, single ...

Embodiment 2

[0849] Example 2: (2S,3S)-N,2-dihydroxy-5-methyl-3-{[4-(3-phenyl-1,2,4-thiadiazol-5-yl)-1 -piperazinyl]carbonyl}hexanamide (2)

[0850]

[0851] Step a) Formation of (5S)-2,2-dimethyl-5-((1S)-3-methyl-1-{[4-(3-phenyl-1,2,4-thiadiazole- 5-yl)-1-piperazinyl]carbonyl}butyl)-1,3-dioxolan-4-one

[0852]

[0853] To (2S)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-4-methylpentanoic acid pentafluorophenyl ester and ( 2R)-2-[(4S)-2,2-Dimethyl-5-oxo-1,3-dioxolan-4-yl]-4-methylpentanoic acid pentafluorophenyl ester (intermediate 1 ; 150.0 mg; 0.38 mmol; 1.0 equiv) to a solution of the 55 / 45 diastereoisomer mixture in DMF (1.5 mL) was added 3-phenyl-5-piperazinyl-1,2,4-thia Oxadiazole (93.2 mg; 0.38 mmol; 1.0 eq) and the resulting reaction mixture was stirred at room temperature for 14 hours. Aqueous HCl (1 N) was added, the resulting mixture was extracted with EtOAc, and dissolved in MgSO 4 Dry, filter and evaporate to an oil. Residue with CD 3 OD extraction. The prec...

Embodiment 3

[0856] Example 3: (2S,3S)-N,2-dihydroxy-5-methyl-3-({(2R)-2-methyl-4-[4-(trifluoromethyl)pyridine-2- Base]piperazin-1-yl}carbonyl)caproamide (3)

[0857]

[0858] Step a) Formation of (5S)-2,2-dimethyl-5-[(1S)-3-methyl-1-({(2R)-2-methyl-4-[4-(trifluoroform Base) pyridin-2-yl] piperazin-1-yl} carbonyl) butyl] -1,3-dioxolan-4-one

[0859]

[0860] To (2S)-2-[(4S)-2,2-dimethyl-5-oxo-1,3-dioxolan-4-yl]-4-methylpentanoic acid pentafluorophenyl ester and ( 2R)-2-[(4S)-2,2-Dimethyl-5-oxo-1,3-dioxolan-4-yl]-4-methylpentanoic acid pentafluorophenyl ester (intermediate 1 ; 484.8mg; 1.22mmol; 1.0eq) of the 55 / 45 diastereomer mixture and triethylamine (339.13μl; 2.45mmol; 2.0eq) in DMF (10.0mL) was added (3R)-3- Methyl-1-[4-(trifluoromethyl)pyridin-2-yl]piperazine (Intermediate 9; 300 mg; 1.22 mmol; 1.0 equiv). After 14 hours of reaction at room temperature, the solvent was evaporated and the residue was dissolved in ether and extracted with water (3x). The combined organic l...

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 relates to N-hydroxylamide derivatives shown in formula (I) and applications thereof, specifically for the treatment and / or prevention of autoimmune diseases, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, cancer, respiratory diseases and Fibrosis, including multiple sclerosis, arthritis, emphysema, chronic obstructive pulmonary disease, liver and pulmonary fibrosis.

Description

field of invention [0001] The present invention relates to N-hydroxyamide derivatives shown in formula (I), their pharmaceutical composition, their preparation method, and relate to their use in the treatment and / or prevention of autoimmune diseases, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases , cancer, respiratory disease and fibrosis. In particular, the present invention relates to N-hydroxyamide derivatives which modulate, especially inhibit, the activity or function of matrix metalloproteases, especially gelatinases and metalloelastases. Background of the invention [0002] Metalloproteases are a superfamily of proteases (enzymes) named for their dependence on a metal ion (zinc) at the active site. [0003] Matrix metalloproteinases (MMPs) are a subfamily of metalloproteases, one of their main biological functions is to catalyze desmoplasia through their ability to hydrolyze various components of tissues or matrices such as collagen, gelat...

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): C07D213/74C07D285/08C07D295/18C07D239/42C07D487/08C07D211/58C07D401/12C07D211/46C07D215/46C07D241/20A61K31/496A61P29/00
CPCC07D211/46C07D211/58C07D213/74C07D215/46C07D239/42C07D241/20C07D285/08C07D295/185C07D401/12C07D487/08A61P1/04A61P1/16A61P1/18A61P11/00A61P11/06A61P15/00A61P15/06A61P17/00A61P25/28A61P29/00A61P35/00A61P37/00A61P43/00A61P9/00C07D241/04C07D401/04C07D417/04
Inventor D·斯维能A·邦布伦J·冈萨雷斯S·克罗斯格纳尼P·戈布C·乔兰德-勒布伦
Owner MERCK PATENT GMBH
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