285984-50-1

Upstream product

• 285984-35-2 [4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]carbamic acid tert-butyl ester 
• 501083-98-3 4-(2-([1]-naphthyloxy-[4]-acetamido)ethyl)morpholine 

Downstream Products

• 1242064-65-8 1-(4-chloro-3-(trifluoromethyl)phenyl)-3-(4-(2-morpholinoethoxy)-naphthalen-1-yl)urea 
• 611168-76-4 1-(1-(3-aminophenyl)-3-(tert-butyl)-1H-pyrazol-5-yl)-3-(4-(2-morpholinoethoxy)naphthalen-1-yl)urea 
• 1609257-17-1 1-(3-(tert-butyl)-1-(3-((2-ethoxyethyl)amino)phenyl)-1H-pyrazol-5-yl)-3-(4-(2-morpholinoethoxy)naphthalen-1-yl)urea 
• 1609257-18-2 N-(3-(3-(tert-butyl)-5-(3-(4-(2-morpholinoethoxy)naphthalen-1-yl)ureido)-1H-pyrazol-1-yl)phenyl)propionamide 
• 611168-85-5 1-[2-(3-nitrophenyl)-5-tert-butyl-2H-pyrazol-3-yl]-3-[4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl]-urea 

Relevant academic research and scientific papers

Development of a fluorescent-tagged kinase assay system for the detection and characterization of allosteric kinase inhibitors

Kinase disregulation disrupts the intricate network of intracellular signaling pathways and contributes to the onset of diseases such as cancer. Although several kinase inhibitors are on the market, inhibitor selectivity and drug resistance mutations persist as fundamental challenges in the development of effective long-term treatments. Chemical entities binding to less conserved allosteric sites would be expected to offer new opportunities for scaffold development. Because no high-throughput method was previously available, we developed a fluorescence-based kinase binding assay for identifying and characterizing ligands which stabilize the inactive kinase conformation. Here, we present a description of the development and validation of this assay using the serine/threonine kinase p38R. By covalently attaching fluorophores to the activation loop of the kinase, we were able to detect conformational changes and measure the Kd, kon, and koff associated with the binding and dissociation of ligands to the allosteric pocket. We report the SAR of a synthesized focused library of pyrazolourea derivatives, a scaffold known to bind with high affinity to the allosteric pocket of p38R. Additionally, we used protein X-ray crystallography together with our assay to examine the binding and dissociation kinetics to characterize potent quinazoline- and quinoline-based type II inhibitors, which also utilize this binding pocket in p38α. Last, we identified the b-Raf inhibitor sorafenib as a potent low nanomolar inhibitor of p38α and used protein X-ray crystallography to confirm a unique binding mode to the inactive kinase conformation.

SILICON COMPOUNDS AND THEIR USE

A compound of formula (1) wherein R1, R2 and R3 are the same or different and are each alkyl, -alkyl-aryl or -alkyl-cycloalkyl; or R1-Si-R 2 taken together form heterocycloalkyl; R4 is aryl

Preparation of 4-amino-1-naphthol ethers

The present invention describes a process for preparing 4-amino-1-naphthol ethers which is characterized in that naphthol ethers are first prepared from 1-naphthols, the former are then converted to the corresponding 4-acetamino-1-naphthol ethers and then the acyl group is cleaved off, and further describes 4-acetamino-1-naphthol ethers obtained thereby.