55977-10-1

Usage

Preparation

Synthesis of 3-bromo-7-hydroxy-4-methyl-2H-chromen-2-one: 4-Methyl-7-hydroxy coumarin was added to acetic acid and stirred for 40 min. Potassium bromate was added to the reaction mixture stirred for 90 min to dissolve completely. Potassium bromide was charged and further stirred for 2 h. The reaction mixture was poured into cold water and stirred for half an hour, filtered and washed with water and recrystallized using ethanol.

InChI:InChI=1/C10H7BrO3/c1-5-7-3-2-6(12)4-8(7)14-10(13)9(5)11/h2-4,12H,1H3

Upstream product

• 84911-18-2 ethyl 2-bromoacetoacetate 
• 108-46-3 recorcinol 
• 90-33-5 7-hydroxy-4-methyl-chromen-2-one 
• 7726-95-6 bromine 
• 64-19-7 acetic acid 
• 75908-67-7 3-bromo-7-methoxy-4-methylcoumarin 
• 2555-28-4 4-methyl-7-methoxy-2H-1-benzopyran-2-one 
• 15481-39-7 dioxane dibromide 
• 848850-50-0 7-triisopropylsilyloxy-4-methylcoumarin 
• 848850-51-1 3-bromo-4-methyl-7-triisopropylsilanyloxy-chromen-2-one 

Relevant academic research and scientific papers

Discovery of Potent Coumarin-Based Kinetic Stabilizers of Amyloidogenic Immunoglobulin Light Chains Using Structure-Based Design

In immunoglobulin light-chain (LC) amyloidosis, transient unfolding or unfolding and proteolysis enable aggregation of LC proteins, causing potentially fatal organ damage. A drug that kinetically stabilizes LCs could suppress aggregation; however, LC sequences are variable and have no natural ligands, hindering drug development efforts. We previously identified high-throughput screening hits that bind to a site at the interface between the two variable domains of the LC homodimer. We hypothesized that extending the stabilizers beyond this initially characterized binding site would improve affinity. Here, using protease sensitivity assays, we identified stabilizers that can be divided into four substructures. Some stabilizers exhibit nanomolar EC50 values, a 3000-fold enhancement over the screening hits. Crystal structures reveal a key π-πstacking interaction with a conserved tyrosine residue that was not utilized by the screening hits. These data provide a foundation for developing LC stabilizers with improved binding selectivity and enhanced physicochemical properties.

A Copper Halide Promoted Regioselective Halogenation of Coumarins Using N-Halosuccinimide as Halide Source

A safe, convenient, and regioselective synthesis of 3-halo coumarins using a metal halide (CuX 2 alone or with ZnX 2) promoted halogenation with N -halosuccinimide (NXS) as halide source is reported. The synthesis involved the steady in situ generation of highly reactive positive halogen (X +) by the coordination of copper or zinc with the N -halosuccinimide and subsequent electrophilic aromatic substitution of the electron-deficient coumarins. This procedure works well also for the halogenation of less electron-rich naphthoquinones, flavones, and methoxypsoralen in moderate to quantitative yields. This protocol features simple experimental conditions using readily available inexpensive reagents and provides a convenient approach to the chlorination or bromination of some useful heteroaromatic compounds.

1,2,3,4-Tetrahydroisoquinoline/2H-chromen-2-one conjugates as nanomolar P-glycoprotein inhibitors: Molecular determinants for affinity and selectivity over multidrug resistance associated protein 1

A series of coniugates bearing a 1,2,3,4-tetrahydroisoquinoline motif linked to substituted 7-hydroxy-2H-chromen-2-ones was synthesized and assayed through calcein-AM test in Madin-Darby Canine Kidney (MDCK) cells overexpressing P-glycoprotein (P-gp) and closely related multidrug resistance associated protein 1 (MRP1) to probe the interference with efflux mechanisms mediated by P-gp and MRP1, respectively. A number of substituents at C3 and C4 of coumarin nucleus along with differently sized and shaped spacers was enrolled to investigate the effects of focused structural modifications over affinity and selectivity. Linker length and flexibility played a key role in enhancing P-gp affinity as proved by the most potent P-gp modulator (3h, IC50 = 70 nM). A phenyl ring within the spacer (3k, 3l, 3o) and bulkier groups (Br in 3r, Ph in 3u) at coumarin C3 led to derivatives showing nanomolar activity (160 nM 50 350). Molecular docking calculations carried out on a human MDR1 homology model structure contributed to gain insights into the ligands’ binding modes. Some compounds (3d, 3h, 3l, 3r, 3t, 3u) reversed MDR thereby restoring doxorubicin cytotoxicity when co-administered with the drug into MDCK-MDR1 cells.

Preparation and pharmacological effects of coumarin derivative and application of coumarin derivative to treatment on pruritus

The invention relates to preparation of a coumarin derivative 7,8-dihydroxy-4-trifluoromethyl-chromene-2H-chromen-2-one for treating the pruritus symptom, studies of pharmacodynamics on the aspects of a molecular pharmacology mechanism, a pruritus animal model and the like of the coumarin derivative, and a pharmaceutics study applicable to treatment on pruritus. The active compound is definite in pharmacological effect mechanism, is broad-spectrum and effective to treat the pruritus symptom, and can be used for clinical application to treatment on skin diseases.

Dioxane dibromide mediated bromination of substituted coumarins under solvent-free conditions

An efficient solvent-free protocol for regioselective bromination of substituted coumarins has been developed by using dioxane dibromide as the solid brominating agent. The efficacy of the solvent-free protocol has been established. The effects of the electronic nature and location of the substituents on the outcome of the reaction have been rationalized with a proposed mechanism.

Studies in synthesis of new psoralenamines

(Chemical Equation Presented) New amino psoralen derivatives have been synthesized via bromination. Bromination of 3,5-substituted psoralens has been studied. The second position of the furan ring is more susceptible to bromination than the α-position of

Simple catalyst-free regio- and chemoselective monobromination of aromatics using NBS in polyethylene glycol

NBS in polyethylene glycol has been efficiently utilized for regio- and chemoselective bromination of activated aromatics at room temperature to form the corresponding bromo products in excellent yields. Copyright Taylor & Francis Group, LLC.

A fluorogenic aldehyde bearing a 1,2,3-triazole moiety for monitoring the progress of aldol reactions

We have developed a new type of fluorogenic aldehyde bearing a 1,2,3-triazole moiety that is useful for monitoring the progress of aldol reactions through an increase in fluorescence. Whereas 6-methoxy-2naphthaldehyde was highly fluorescent, the fluorogenic aldehyde, 4-formylbenzene connected to the 6-methoxy-2-naphthyl group through a 1,2,3-triazole moiety, was essentially nonfluorescent in aqueous solutions. We suggest that the 4-formylphenyl group acts as a quencher to suppress the fluorescence of the 6-methoxy-2- naphthyltriazole moiety. The product of the aldol reaction of this aldehyde does not have a quenching moiety and showed more than 800-fold higher fluorescence than the aldehyde. Assay systems using the fluorogenic aldehyde were validated by screening of aldol catalysts, ranking of the activities of the catalysts, and evaluation of reaction conditions.

An efficient, rapid and regioselective nuclear bromination of aromatics and heteroaromatics with NBS using sulfonic-acid-functionalized silica as a heterogeneous recyclable catalyst

A simple, efficient and rapid method has been developed for high-yielding regioselective nuclear monobromination of aromatic and heteroaromatic compounds using NBS in the presence of sulfonic-acid-functionalized silica at room temperature. The catalyst works under heterogeneous conditions and can be recycled.

α:β Selectivity in the synthesis of 3-substituted, 4-methyl umbelliferone glycosides of N-acetyl glucosamine and chitobiose

The influence of phenolic acceptor nucleophilicity; for example, 3-substituted, 4-methylumbelliferones, and glycosyl donor electrophilicity; for example, 3- and 4-substituted N-acetylglucosamines, on glycosylation stereochemistry has been evaluated. In a systematic comparison, the stereochemical outcome as well as the reaction yield appeared to be influenced by the 3- and 4-substituents of the donor as well as the 3-substituent of the aryl acceptor. In the context of synthesizing a fluorogenic substrate for oligosaccharyltransferase, an α-glycoside was desired. Although most acceptor-donor pairs led to predominantly or exclusively the β-glycoside, reaction of the most activated (3,4-di-O-benzyl) donor and the least nucleophilic acceptor (3-Br), resulted in a 1:1 ratio of α,β arylglycosides.