1449277-10-4

Basic information

• Product Name: GNE-495
• Synonyms: GNE-495;8-Amino-N-[1-(cyclopropylcarbonyl)-3-azetidinyl]-2-(3-fluorophenyl)-1,7-naphthyridine-5-carboxamide
• CAS NO: 1449277-10-4
• Molecular Formula: C₂₂H₂₀FN₅O₂
• Molecular Weight: 405.4249032
• EINECS: -0
• Mol File: 1449277-10-4.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 734.5±60.0 °C(Predicted)
• Appearance: /
• Density: 1.45±0.1 g/cm3(Predicted)
• PKA: 11.60±0.20(Predicted)
• CAS DataBase Reference: GNE-495(CAS DataBase Reference)
• NIST Chemistry Reference: GNE-495(1449277-10-4)
• EPA Substance Registry System: GNE-495(1449277-10-4)

Safety Data

• Hazardous Substances Data: 1449277-10-4(Hazardous Substances Data)

Usage

General Description

GNE-495 is a potent and selective inhibitor of leucine-rich repeat kinase 2 (LRRK2), a protein involved in the pathogenesis of Parkinson's disease. It has been developed as a potential therapeutic agent for the treatment of Parkinson's disease and potentially other neurodegenerative disorders. GNE-495 has shown promising results in preclinical studies, demonstrating the ability to decrease LRRK2 activity and reduce the accumulation of toxic alpha-synuclein aggregates, a hallmark of Parkinson's disease. The compound has also exhibited favorable pharmacokinetic properties and good brain penetration, making it a promising candidate for further development as a disease-modifying therapy for Parkinson's and other neurodegenerative illnesses.

Upstream product

• 1449278-68-5 tert-butyl N-[1-(cyclopropanecarbonyl)azetidin-3-yl]carbamate 
• 1339749-29-9 (3-aminoazetidin-1-yl)cyclopropylmethanone 
• 1449278-53-8 8-amino-2-(3-fluorophenyl)-1,7-naphthyridine-5-carboxylic acid 
• 1449277-90-0 ethyl 8-amino-2-(3-fluorophenyl)-1,7-naphthyridine-5-carboxylate 
• 1449278-46-9 5-bromo-7-(2-trimethylsilylethoxymethyl)-1,7-naphthyridin-8-one 
• 1449278-47-0 ethyl 8-oxo-7-(2-trimethylsilylethoxymethyl)-1,7-naphthyridine-5-carboxylate 
• 1449278-48-1 ethyl 1-oxido-8-oxo-7-(2-trimethylsilylethoxymethyl)-1,7-naphthyridin-1-ium-5-carboxylate 
• 1449278-49-2 ethyl 2-chloro-8-oxo-7-(2-trimethylsilylethoxymethyl)-1,7-naphthyridine-5-carboxylate 
• 1449278-50-5 ethyl 2-(3-fluorophenyl)-8-oxo-7-(2-trimethylsilylethoxymethyl)-1,7-naphthyridine-5-carboxylate 
• 1449278-51-6 ethyl 2-(3-fluorophenyl)-8-oxo-7H-1,7-naphthyridine-5-carboxylate 
• 1449278-52-7 ethyl 8-chloro-2-(3-fluorophenyl)-1,7-naphthyridine-5-carboxylate 
• 67967-14-0 5-bromo-7,8-dihydro-1,7-naphthyridin-8-one 
• 41404-58-4 2-bromo-5-fluoropyridine 
• 768-35-4 3-fluorophenylboronic acid 

Relevant articles and documents

MAP4K4 regulates integrin-FERM binding to control endothelial cell motility

Cell migration is a stepwise process that coordinates multiple molecular machineries. Using in vitro angiogenesis screens with short interfering RNA and chemical inhibitors, we define here a MAP4K4-moesin-talin-? 21-integrin molecular pathway that promotes efficient plasma membrane retraction during endothelial cell migration. Loss of MAP4K4 decreased membrane dynamics, slowed endothelial cell migration, and impaired angiogenesis in vitro and in vivo. In migrating endothelial cells, MAP4K4 phosphorylates moesin in retracting membranes at sites of focal adhesion disassembly. Epistasis analyses indicated that moesin functions downstream of MAP4K4 to inactivate integrin by competing with talin for binding to ? 21-integrin intracellular domain. Consequently, loss of moesin (encoded by the MSN gene) or MAP4K4 reduced adhesion disassembly rate in endothelial cells. Additionally, ?± 5? 21-integrin blockade reversed the membrane retraction defects associated with loss of Map4k4 in vitro and in vivo. Our study uncovers a novel aspect of endothelial cell migration. Finally, loss of MAP4K4 function suppressed pathological angiogenesis in disease models, identifying MAP4K4 as a potential therapeutic target.

ISOQUINOLINE AND NAPHTHYRIDINE DERIVATIVES

The invention provides novel compounds having the general formula(I) wherein A, R1 and R2 are as described herein, compositions including the compounds and use of the compounds for inhibiting angiogenesis by inhibition of MAP4K4.