26717-39-5

Basic information

• Product Name: [[(3,4-Dimethoxyphenyl)amino]methylene]malonic acid,diethyl ester
• Synonyms: [[(3,4-Dimethoxyphenyl)amino]methylene]malonic acid,diethyl ester
• CAS NO: 26717-39-5
• Molecular Weight: 323.346
• Mol File: 26717-39-5.mol

Chemical Properties

• CAS DataBase Reference: [[(3,4-Dimethoxyphenyl)amino]methylene]malonic acid,diethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: [[(3,4-Dimethoxyphenyl)amino]methylene]malonic acid,diethyl ester(26717-39-5)
• EPA Substance Registry System: [[(3,4-Dimethoxyphenyl)amino]methylene]malonic acid,diethyl ester(26717-39-5)

Safety Data

• Hazardous Substances Data: 26717-39-5(Hazardous Substances Data)

Upstream product

• 87-13-8 diethyl 2-ethoxymethylenemalonate 
• 6315-89-5 3,4-dimethoxyaniline 

Downstream Products

• 13436-14-1 ethyl 4-hydroxy-6,7-dimethoxyquinoline-3-carboxylate 
• 13436-14-1 ethyl 6,7-dimethoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylate 
• 26893-22-1 4-hydroxy-6,7-dimethoxy-2-quinolinecarboxylic acid 
• 13425-93-9 6,7-dimethoxyquinoline-4-ol 
• 417722-21-5 5-((6,7-dimethoxyquinolin-4-yl)oxy)pyridine-2-amine 
• 1373767-25-9 ethyl 6,7-dimethoxy-4-oxo-2-(3-phenoxyphenyl)-1,4-dihydroquinoline-3-carboxylate 
• 1373767-24-8 ethyl 6,7-dimethoxy-2-(3-methoxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate 
• 1373767-23-7 ethyl 2-([1,1'-biphenyl]-3-yl)-6,7-dimethoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate 
• 214470-41-4 4-[(3-bromophenyl)amino]-6,7-dimethoxy-3-quinolinecarboxylic acid ethyl ester 
• 214470-50-5 4-[(3-bromophenyl)amino]-6,7-dimethoxy-3-quinolinecarboxamide 
• 214470-49-2 4-[(3-bromophenyl)amino]-6,7-dimethoxy-3-quinolinecarboxylic acid 
• 294175-27-2 [4-(3-bromo-phenylamino)-6,7-dimethoxy-quinolin-3-yl]-methanol 

Relevant articles and documents

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Type-1 ryanodine receptor (RyR1) is a calcium-release channel localized on sarcoplasmic reticulum (SR) of the skeletal muscle, and mediates muscle contraction by releasing Ca2+ from the SR. Genetic mutations of RyR1 are associated with skeletal muscle diseases such as malignant hyperthermia and central core diseases, in which over-activation of RyR1 causes leakage of Ca2+ from the SR. We recently developed an efficient high-throughput screening system based on the measurement of Ca2+ in endoplasmic reticulum, and used it to identify oxolinic acid (1) as a novel RyR1 channel inhibitor. Here, we designed and synthesized a series of quinolone derivatives based on 1 as a lead compound. Derivatives bearing a long alkyl chain at the nitrogen atom of the quinolone ring and having a suitable substituent at the 7-position of quinolone exhibited potent RyR1 channel-inhibitory activity. Among the synthesized compounds, 14h showed more potent activity than dantrolene, a known RyR1 inhibitor, and exhibited high RyR1 selectivity over RyR2 and RyR3. These compounds may be promising leads for clinically applicable RyR1 channel inhibitors.

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Malaria is a protozoal parasitic disease that is widespread in tropical and subtropical regions of Africa, Asia, and the Americas and causes more than 800,000 deaths per year. The continuing emergence of multidrug-resistant Plasmodium falciparum drives the ongoing need for the development of new and effective antimalarial drugs. Our previous work has explored the preliminary structural optimization of 4(1H)-quinolone ester derivatives, a new series of antimalarials related to the endochins. Herein, we report the lead optimization of 4(1H)-quinolones with a focus on improving both antimalarial potency and bioavailability. These studies led to the development of orally efficacious antimalarials including quinolone analogue 20g, a promising candidate for further optimization.

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