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

Inhibitors of LRRK2 kinase activity

A technology of -CR5R6R7, -OR9, applied in the field of inhibitors of LRRK2 kinase activity

Inactive Publication Date: 2014-07-09
ELAN PHARM INC
View PDF13 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Such LRRK2 inhibitors for the treatment of PD and other LBDs are not well known

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
  • Inhibitors of LRRK2 kinase activity
  • Inhibitors of LRRK2 kinase activity
  • Inhibitors of LRRK2 kinase activity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0632]Synthesis of 4-amino-7-(4-(methylsulfonyl)phenyl)cinnoline-3-carboxamide (5)

[0633] 4-Amino-7-(4-(methylsulfonyl)phenyl)cinnoline-3-carboxamide (5) is prepared from 3-chloroaniline (1) in the following 3 steps:

[0634]

[0635] Step 1- Synthesis of 2-((3-chlorophenyl)diazenyl)-2-cyanoacetamide (2): 3-chloroaniline (1,7.4g, 58.1mmol ), and 15 mL of concentrated HCl was slowly added, followed by 10 mL of water to give a slurry. Sodium nitrite (4.0 g in 15 mL of water, 58.1 mmol) was added at 0°C. After stirring at 0 °C for 15 min, a solution of sodium acetate (19.1 g, 232 mmol) and cyanoacetamide (4.89 g, 58.1 mmol) in 85 mL of water and 60 mL of ethanol was added slowly using an addition funnel. After the addition was complete, the ice bath was removed and the suspension was slowly warmed to 23 °C and stirred for 16 h. The desired material was isolated by filtration and washed with water, ethanol and Et 2 Rinse with O, then dry under vacuum to obtain the desired...

Embodiment 2

[0650] 4-(isopropylamino)-7-(4-(methylsulfonyl)phenyl)cinnoline-3-carboxamide (17) and 4-(isopropylamino)-7-(4-(methylsulfonyl) Synthesis of sulfonyl)phenyl)cinnoline-3-carbonitrile (18)

[0651] 4-(Isopropylamino)-7-(4-(methylsulfonyl)phenyl)cinnoline-3-carboxamide is prepared from 3-iodoaniline (10) in 6 or 7 steps as follows (17) and 4-(isopropylamino)-7-(4-(methylsulfonyl)phenyl)cinnoline-3-carboxamide (18):

[0652]

[0653] Synthesis of step 1-2-cyano-2-((3-iodophenyl)diazenyl)acetamide (11): 3-iodoaniline (10, 12.7g, 58.1mmol ), and reacted similarly to step 1 of Example 1 to obtain the desired compound (11,70%).

[0654] Synthesis of step 2-4-amino-7-iodocinoline-3-carboxamide (12): 2-cyano-2-((3-iodophenyl)diazenyl)acetamide is filled into a 20mL reaction bottle (11,1 g, 3.2 mmol), and suspended in 13 mL of toluene. Add 5 spoonfuls of AlCl 3 , and seal the vial under nitrogen. The heterogeneous reaction mixture was heated to 150 °C for 20 min using microwave ...

Embodiment 3

[0842] Synthesis of N-isopropyl-7-(4-(methylsulfonyl)phenyl)-3-(thiazol-4-yl)cinnolin-4-amine (70)

[0843] N-isopropyl-7-(4-(methylsulfonyl)phenyl)-3-(thiazole-4- base) cinnolin-4-amine (70):

[0844]

[0845] Synthesis of step 1-4-bromo-2-nitrobenzoyl chloride (60): 4-bromo-2-nitrobenzoic acid (59,10g, 40.6mmol) was dissolved in 133mL THF, and the resulting solution was Cool to 0 °C. Oxalyl chloride (7.09 mL, 81.3 mmol) was added over 5 minutes, followed by 2 drops of DMF, and the reaction mixture was heated to reflux for 3 hours, after which time the solution was concentrated and dried under vacuum to afford the desired compound 60.

[0846] Step 2- Synthesis of 2-(4-bromo-2-nitrobenzoyl) diethyl malonate (61): Diethyl malonate (6.16mL, 40.6mmol) was dissolved in 50mL THF, And the resulting solution was cooled to 0 °C. Sodium hydride (1.94 g a 60% suspension, 48.7 mmol) was added in portions over 30 minutes and the resulting mixture was heated to reflux for 2 hours. ...

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 compounds having a structure according to Formula I: (I) or a salt or solvate thereof, wherein R1, R2, R3 and R4 are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Provisional Application Serial No. 61 / 519,443, entitled "Inhibitors of LRRK2 Kinase Activity," filed May 23, 2011, which is incorporated herein by reference in its entirety. Background technique [0003] Parkinson's disease (PD), the most common form of Parkinson's disease, is a neurodegenerative movement characterized by resting tremor, rigidity, postural instability, impaired speech and bradykinesia (slow movement) obstacle. In addition to PD, Parkinson's disease manifests in conditions such as progressive supranuclear palsy, corticobasal degeneration, multiple system atrophy, and dementia with Lewy bodies. James Parkinson first described PD in 1817 in his monograph entitled "An Essay on the Shaking Palsy" (Parkinson, J.; J. Neuropsychiatry Clin. Neurosci. 2002, 14 (2), 223-236 (reprinted )). Symptoms of this particular disorder include involuntary tremors, decreased muscle str...

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): C07D237/28C07D403/04C07D417/04C07D401/04C07D403/10A61K31/502C07D401/10C07D405/04A61P25/16C07D401/12C07D405/10A61P25/28C07D401/14C07D405/12A61P37/00
CPCC07D237/28C07D401/04C07D401/10C07D401/12C07D401/14C07D403/04C07D403/10C07D405/12C07D413/04C07D413/10C07D417/04C07D405/04C07D405/10A61P1/04A61P25/00A61P25/16A61P25/28A61P37/00A61P37/06A61P43/00A61K31/502A61K31/506A61K31/5377
Inventor D·L·奥伯莱A·W·加罗法洛S·鲍尔A·P·张X·M·叶M·弗兰齐尼M·阿德莱尔J·R·尼兹G·普罗布斯特
Owner ELAN PHARM INC
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