26832-89-3

Upstream product

• 87-13-8 diethyl 2-ethoxymethylenemalonate 
• 95-76-1 m,p-dichloroaniline 

Downstream Products

• 1373767-31-7 ethyl 2-([1,1'-biphenyl]-3-yl)-6,7-dichloro-4-oxo-1,4-dihydroquinoline-3-carboxylate 
• 1373767-32-8 ethyl 6,7-dichloro-2-(3-methoxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate 
• 1373767-33-9 ethyl 6,7-dichloro-4-oxo-2-(3-phenoxyphenyl)-1,4-dihydroquinoline-3-carboxylate 

Relevant academic research and scientific papers

Lead optimization of 3-carboxyl-4(1 H)-quinolones to deliver orally bioavailable antimalarials

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.

Insights into supramolecular assembly formation of diethyl aryl amino methylene malonate (DAM)derivatives assisted via non-covalent interactions

The crystal structures of four derivatives of diethyl 2-(((aryl)amino)methylene)malonate (DAM)have been studied by single crystal X-ray diffraction. The molecular structures of all the four derivatives were found to be in co-planar conformation. The detailed analysis of molecular conformation in four derivatives reveals the presence of a common strong intramolecular N–H?O hydrogen bonding, forming a ring of graph-set motif S1 1 (6). The effect of chloro and nitro substitution on their relative strengths of hydrogen bonding are analyzed here. Particularly, in compound 1, additional intramolecular hydrogen bonding between –NO2 and N–H was observed that results in the formation of another six-membered chelate ring. On the other hand in case of compound 3, we have observed type-I Cl?Cl interaction for the first time in this class of compounds. Further, Hirshfeld surface has been generated that is mapped with dnorm shape index and curvedness to summarize the weak interactions and examine the molecular shapes in all four derivatives. Effect of nitro (1 and 2)and chloro (3 and 4)substitution on the C?H, N?O and C?O interaction is highlighted in molecular contour and 2D fingerprint plots.

Operative conversions of 3-carboxy-4-quinolones into 3-nitro-4-quinolones via ipso-nitration: Potential antifilarial agents as inhibitors of Brugia malayi thymidylate kinase

An efficient, cost effective and green methodology for ipso nitration in the synthesis of the 3-nitro derivative of 3-carboxy 4-quinolones has been developed by the quantitative use of copper acetate and silver nitrate in water. The observed regioselectivity of nitration is explained by the DFT calculations. Three of these compounds with IC50 values (2.9-3.4 μmol) against Brugia malayi thymidylate kinase may be good antifilarial agents as also evidenced by molecular docking studies.

An NMR study of halogenated 1,4-dihydro-1-ethyl-4-oxoquinoline-3-carboxylates

Ethyl 1,4-dihydro-1-ethyl-4-oxoquinoline-3-carboxylate and 29 of its mono-, di-and tri-fluoro and/or -chloro derivatives were synthesized and their 1H, 13C and 19F NMR spectra were recorded. 1H, 13C and 19F chemical shifts, JHH, JFH, JCF and JFF coupling constants are reported. The 13C substituent chemical shift values of the chloro and fluoro substituents were calculated by linear multiple regression.