548764-04-1

Upstream product

• 88023-07-8 ethyl 2-<(4-fluorophenyl)methyl>-3-oxobutanoate 
• 108-46-3 recorcinol 
• 459-46-1 4-Fluorobenzyl bromide 
• 141-97-9 ethyl acetoacetate 

Downstream Products

• 548764-89-2 morpholine-4-carboxylic acid 3-(4-fluorobenzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester 
• 548764-77-8 3,4-Dihydro-2H-quinoline-1-carboxylic acid 3-(4-fluoro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester 
• 1428238-89-4 3-(4-fluorobenzyl)-4-methyl-2-oxo-2H-chromen-7-yl acetate 
• 1428238-90-7 3-(4-fluorobenzyl)-4-methyl-2-oxo-2H-chromen-7-yl propionate 
• 883021-86-1 3-(4-fluorobenzyl)-4-methyl-2-oxo-2H-chromen-7-yl pivalate 
• 1428239-18-2 3-(4-fluorobenzyl)-4-methyl-2-oxo-2H-chromen-7-yl benzoate 
• 1428238-91-8 3-(4-fluorobenzyl)-4-methyl-2-oxo-2H-chromen-7-yl butyrate 
• 1428239-17-1 3-(4-fluorobenzyl)-4-methyl-2-oxo-2H-chromen-7-yl 4-methylbenzenesulfonate 
• 548764-03-0 methyl-phenyl-carbamic acid 3-(4-fluorobenzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester 

Relevant academic research and scientific papers

Development of coumarine derivatives as potent anti-filovirus entry inhibitors targeting viral glycoprotein

Filoviruses, including Ebolavirus (EBOV), Marburgvirus (MARV) and Cuevavirus, cause hemorrhagic fevers in humans with up to 90% mortality rates. In the 2014–2016 West Africa Ebola epidemic, there are 15,261 laboratory confirmed cases and 11,325 total deaths. The lack of effective vaccines and medicines for the prevention and treatment of filovirus infection in humans stresses the urgency to develop antiviral therapeutics against filovirus-associated diseases. Our previous study identified a histamine receptor antagonist compound CP19 as an entry inhibitor against both EBOV and MARV. The preliminary structure-activity relationship (SAR) studies of CP19 showed that its piperidine, coumarin and linker were related with its antiviral activities. In this study, we performed detailed SAR studies on these groups with synthesized CP19 derivatives. We discovered that 1) the piperidine group could be optimized with heterocycles, 2) the substitution groups of C3 and C4 of coumarin should be relatively large hydrophobic groups and 3) the linker part should be least substituted. Based on the SAR analysis, we synthesized compound 32 as a potent entry inhibitor of EBOV and MARV (IC50 = 0.5 μM for EBOV and 1.5 μM for MARV). The mutation studies of Ebola glycoprotein and molecular docking studies showed that the coumarin and its substituted groups of compound 32 bind to the pocket of Ebola glycoprotein in a similar way to the published entry inhibitor compound 118a. However, the carboxamide group of compound 32 does not have strong interaction with N61 as compound 118a does. The coumarin skeleton structure and the binding model of compound 32 elucidated by this study could be utilized to guide further design and optimization of entry inhibitors targeting the filovirus glycoproteins.

Novel Nitric Oxide Donors of Phenylsulfonylfuroxan and 3-Benzyl Coumarin Derivatives as Potent Antitumor Agents

In this work, five new hybrids of phenylsulfonylfuroxan merging 3-benzyl coumarin and their seco-B-ring derivatives 2-6 were designed and synthesized. Among them, compound 3 showed the most potent antiproliferation activities with IC50 values range from 0.5 to 143 nM against nine drug-sensitive and four drug-resistant cancer cell lines. Preliminary pharmacologic studies showed that these compounds displayed lower toxicities than that of lead compound 1. Compound 3 obviously induced the early apoptosis and hardly affected the cell cycle of A2780, which was significantly different from compound 1. Especially, it gave 559- and 294-fold selectivity antiproliferation activity in P-gp overexpressed drug-resistant cancer cell lines MCF-7/ADR and KB-V compared to their drug-sensitive ones MCF-7 and KB, implying that compounds 2-6 might have an extra mechanism of anti-MDR-cancer with P-gp overexpression.

3-substituted coumarin furazan derivatives and application of derivatives in preparation of anti-multidrug resistance tumor drugs

The invention belongs to the field of chemical pharmacy, and relates to furazan conjugates obtained by a combination of a 3-substituted coumarin mother nucleus, a derivative substituted by alpha,beta-unsaturated ketone, and furoxan through two-carbon link

Substituted 3-benzylcoumarins as allosteric MEK1 inhibitors: Design, synthesis and biological evaluation as antiviral agents

In order to find novel antiviral agents, a series of allosteric MEK1 inhibitors were designed and synthesized. Based on docking results, multiple optimizations were made on the coumarin scaffold. Some of the derivatives showed excellent MEK1 binding affinity in the appropriate enzymatic assays and displayed obvious inhibitory effects on the ERK pathway in a cellular assay. These compounds also significantly inhibited virus (EV71) replication in HEK293 and RD cells. Several compounds showed potential as agents for the treatment of viral infective diseases, with the most potent compound 18 showing an IC 50 value of 54.57 nM in the MEK1 binding assay.

Discovery and structure-activity relationship of coumarin derivatives as TNF-α inhibitors

The discovery and structure-activity relationship of a novel series of coumarin-based TNF-α inhibitors is described. Starting from the initial lead 1a, various derivatives were prepared surrounding the coumarin core structure to optimize the in vitro inhibitory activity of TNF-α production by human peripheral blood mononuclear cells (hPBMC), stimulated by bacterial lipopolysaccharide (LPS). Selected compounds also demonstrated in vivo inhibition of TNF-α production in rats.