25392-41-0

Basic information

• Product Name: 4-(CHLOROMETHYL)-7-HYDROXY-2H-CHROMEN-2-ONE
• Synonyms: OTAVA-BB BB7014350028;4-(CHLOROMETHYL)-7-HYDROXY-2H-CHROMEN-2-ONE;4-CHLOROMETHYL-7-HYDROXY-CHROMEN-2-ONE;4-(CHLOROMETHYL)-7-HYDROXYCOUMARIN;AKOS BBS-00000158;CELLTRACKER(TM) BLUE CMHC;BlueCMHC;2H-1-Benzopyran-2-one, 4-(chloroMethyl)-7-hydroxy-
• CAS NO: 25392-41-0
• Molecular Formula: C₁₀H₇ClO₃
• Molecular Weight: 210.61
• Mol File: 25392-41-0.mol

Chemical Properties

• Melting Point: 180-183°C
• Boiling Point: 409.6 °C at 760 mmHg
• Flash Point: 201.5 °C
• Appearance: /
• Density: 1.442 g/cm³
• Vapor Pressure: 2.72E-07mmHg at 25°C
• Refractive Index: 1.618
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 7.72±0.20(Predicted)
• CAS DataBase Reference: 4-(CHLOROMETHYL)-7-HYDROXY-2H-CHROMEN-2-ONE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-(CHLOROMETHYL)-7-HYDROXY-2H-CHROMEN-2-ONE(25392-41-0)
• EPA Substance Registry System: 4-(CHLOROMETHYL)-7-HYDROXY-2H-CHROMEN-2-ONE(25392-41-0)

Safety Data

• Hazard Codes: Xi
• HazardClass: IRRITANT
• Hazardous Substances Data: 25392-41-0(Hazardous Substances Data)

Usage

Uses

Fluorescent Thiol-Reactive cell permeant probe

InChI:InChI=1/C10H7ClO3/c11-5-6-3-10(13)14-9-4-7(12)1-2-8(6)9/h1-4,12H,5H2

Upstream product

• 638-07-3 ethyl (2-chloroaceto)acetate 
• 108-46-3 recorcinol 
• 32807-28-6 Methyl 4-chloroacetoacetate 

Downstream Products

• 911290-21-6 7-[ (3-chlorobenzyl)oxy]-4-(chloromethyl)-2H-chromen-2-one 
• 41295-55-0 4-(chloromethyl)-7-methoxy-2H-chromen-2-one 
• 911290-37-4 4-(chloromethyl)-7-[ (3-fluorobenzyl)oxy]-2H-chromen-2-one 
• 1252592-56-5 2-[6-(benzyloxy)benzofuran-3-yl]ethyl 4-methylbenzenesulfonate 
• 1252592-57-6 4-({2-[6-(benzyloxy)benzofuran-3-yl]ethyl}(4H-1,2,4-triazol-4-yl)amino)benzonitrile 
• 1252592-58-7 4-{[2-(6-hydroxybenzofuran-3-yl)ethyl](4H-1,2,4-triazol-4-yl)amino}benzonitrile 
• 1252592-59-8 3-{2-[(4-cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]ethyl}benzofuran-6-yl sulfamate 
• 1252592-54-3 benzyl 2-(6-(benzyloxyl)benzofuran-3-yl)acetate 
• 1252592-55-4 2-[6-(benzyloxy)benzofuran-3-yl]ethanol 
• 1352006-40-6 dibenzyl 4-chloromethyl-2-oxo-2H-chromen-7-yl phosphate 
• 1000413-72-8 [(3S)-6-({2',6'-dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetic acid 
• 1234474-57-7 [(3R)-6-({2',6'-dimethyl-4'-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetic acid 
• 1000414-38-9 methyl ((3S)-6-hydroxy-2,3-dihydro-1-benzofuran-3-yl)acetate 
• 1394138-46-5 [(3S)-6-hydroxy-2,3-dihydro-1-benzofuran-3-yl]acetic acid (1R)-1-phenylethylamine salt 

Relevant articles and documents

1,2,3-Triazole pharmacophore-based benzofused nitrogen/sulfur heterocycles with potential anti-Moraxella catarrhalis activity

Versatile 1,2,3-triazole pharmacophore-based benzofused heterocycles containing halogen-substituted aromatic (9-17 and 25-28), 7-substituted coumarin (18-23 and 29-30) or penciclovir-like subunit (31a,b-38a) were designed and synthesized to evaluate their

Highly Selective Sensing of Li+ in H2O/CH3CN via Fluorescence ‘Turn-on’ Response of a Coumarin-Indole Linked Dyad: an Experimental and Theoretical Study

A coumarin-indole dyad, N-((7-hydroxy-2-oxo-2H-chromen-4-yl)methyl)-1H-indole-2-carboxamide has been synthesized and characterized by 1H-NMR and 13C-NMR. Effect of various metal ions on fluorescent behavior was also studied. The synthesized compound showed remarkable specificity towards Li+ in organo-aqueous medium over other metal ions. Coordination of the compound with Li+ induces a turn-on fluorescence response. The sensor exhibited good binding constant and low detection limit towards Li+. Experimental results have been verified with Density Functional Theory and Time Dependent Density Functional Theory calculations.

Synthesis and biological evaluation of morpholines linked coumarin–triazole hybrids as anticancer agents

A series of novel morpholines linked coumarin–triazole hybrids (6a–6v) has been synthesized and evaluated for their anti-proliferative potential on a panel of five human cancer cell lines, namely bone (MG-63), lung (A549), breast (MDA-MB-231), colon (HCT-15) and liver (HepG2), using MTT assay. Among all, the compound 6n {7-((1-(2,4-dichlorobenzyl)-1H-1,2,3-triazol-4-yl) methoxy)-4-((2,6-dimethylmorpholino) methyl)-2H-chromen-2-one} showed significant growth inhibition against MG-63 cells with an IC50 value of 0.80 ± 0.22 μM. Further, induction of apoptosis by 6n of MG-63 cells confirmed as a result of morphological changes, the sub-G1 phase arrest, increased percentage of apoptotic cells, and decrease in mitochondrial membrane potential and increase in reactive oxygen species levels. The in vitro Gal-1 expression in cell culture supernatant of MG-63 cells treated with compound 6n showed dose-dependent reduction. The binding constant (Ka) of 6n with Gal-1 was calculated from the intercept value which was observed as 3.0 × 105 M?1 by fluorescence spectroscopy. Surface plasmon resonance showed that 6n binds to Gal-1 with binding constant (Ka) of 1.29E+04 1/Ms and equilibrium constant KD value of 7.54E?07 M, respectively. Molecular docking studies revealed the binding interactions of 6n with Gal-1.

Design, synthesis, and characterization of 7-methoxy-4- (aminomethyl)coumarin as a novel and selective cytochrome P450 2D6 substrate suitable for high-throughput screening

In this study, a selective substrate for cytochrome P450 2D6 was designed using a small molecule model developed by M. J. De Groot et al. [(1997) Chem. Res. Toxicol. 10, 41-48]. The substrate, 7-methoxy-4- (aminomethyl)coumarin (MAMC), and its putative O-demethylated metabolite 7- hydroxy-4-(aminomethyl)coumarin (HAMC) were synthesized, and their respective fluorescence properties were characterized. The selectivity of MAMC for P450 2D6 was characterized using microsomes containing single human P450 isoenzymes and human liver microsomes. Formation of the metabolic product HAMC was easily assessed in real time with fluorescence spectroscopy, since MAMC and HAMC excitation and emission wavelengths differed significantly. HPLC analysis confirmed that HAMC was the single metabolic product of MAMC and that HAMC formation accounts for the total increase in fluorescence. It was found that, in microsomes from yeast or lymphoblastoid cells selectively expressing P450 isoenzymes, MAMC was selective for P450 2D6 at a concentration of 25 μM with only P450 1A2 contributing significantly to the formation of HAMC. P450s 2A6, 2B6, 2C8, 2C9, 2C19, 2E1, 3A4, and 3A5 were shown not to metabolize MAMC at a concentration of 25 μM. K(m) and ν(max) values of MAMC for P450 2D6 were found to be 26.2 ± 2.8 μM and 2.9 ± 0.07 min-1, respectively. For P450 1A2, MAMC was found to have a K(m) value of 29.7 ± 6.2 μM and a ν(max) of 0.57 ± 0.07 min-1. Formation of HAMC in human liver microsomes could be completely inhibited by quinidine, at a concentration of 0.5 μM selective for P450 2D6, and furafylline, at a concentration of 30 μM selective for P450 1A2. In conclusion, O- demethylation of 7-methoxy-4-(aminomethyl)coumarin is a rapid and easily determined parameter for P450 2D6 activity and, due to the fluorescent properties of the metabolite formed, may be a valuable new tool for high- throughput screening purposes.

Novel chalcone-conjugated, multi-flexible end-group coumarin thiazole hybrids as potential antibacterial repressors against methicillin-resistant Staphylococcus aureus

The increasing resistance of methicillin-resistant Staphylococcus aureus (MRSA) to antibiotics has led to a growing effort to design and synthesize novel structural candidates of chalcone-conjugated, multi-flexible end-group coumarin thiazole hybrids with

Synthesis and biological evaluation of novel 4,7-disubstituted coumarins as selective tumor-associated carbonic anhydrase IX and XII inhibitors

With an aim to develop novel potential anti-cancer agents we have designed a series of novel 4,7-disubstituted coumarin hybrids synthesis and evaluated for their inhibitory activity against the human carbonic anhydrase isoforms namely CA I, CA II, CA IX and CA XII. The results of CA inhibition clearly showed that the novel 4, 7-disubstituted coumarin hybrids (7a–i & 8a–j) exhibited selective inhibition towards tumor associated isoforms, CA IX and CA XII without inhibiting CA I and CA II isoforms. Among all the compound 8b showed a significant inhibition against hCA IX with a Ki of 0.58 μM whereas, the compound 7c showed a significant inhibition against hCA XII with a Ki of 0.36 μM respectively. All other compounds have shown a good inhibition against hCA IX and hCA XII over hCA I and hCA II within the range of 0.46 to 9.35 μM. Therefore, compound 8b and 7c would be the potential leads for developing selective cytotoxic agents targeting hCA IX and XII.

Synthesis, 18F-radiolabeling and apoptosis inducing studies of novel 4, 7-disubstituted coumarins

In present study, a new series of 4, 7-disubstituted coumarin derivatives (7a-y) have been synthesized as galectin-1 targeting apoptosis inducing agents and evaluated for their in vitro cytotoxic potentials against a panel of selected human cancer cell lines namely, Brest (MCF7), Ovarian (SKOV3), Prostate (PC-3 & DU145) and normal embryonic kidney (HEK293T) cells, using MTT assay. Most of the compounds exhibited potent growth inhibitory action against the treated cancer cell lines with an IC50 range of 10–30 μM. Compound 7q exhibited a significant growth inhibition against prostate cancer (PC-3 & DU145) cell lines with an IC50 value of 7.45 ± 0.03 μM, 8.95 ± 0.17 μM respectively. Further, the target compound 7q was radiolabeled with fluorine-18 [18F] to be used as a novel PET radiotracer for imaging of tumors via targeting galectin-1, using appropriate reaction conditions in the GE Tracer-lab FX2N synthesis module. The purification of the [18F] radiolabeled compound [18F]-7q was successfully achieved with 60% ethanol. The radiochemical purity was>85% and residual solvent limits of DMF was 65 ± 3 ppm as analysed by HPLC, TLC & GC analytical methods. The apoptosis studies confirm the inhibition of cell proliferation with morphological changes like cell shrinkage, blebbing and cell wall deformation, increasing the ROS levels, and loss of mitochondrial membrane potential by Acridine orange/Ethidium bromide staining, Hoechst-33342 staining, H2DCFDA staining, annexin V-FITC/PI, and JC-1 staining methods. In flow cytometric analysis, 7q selectively arrested the sub-G1 phase of the cell cycle in a dose-dependent manner. In Gal-1 ELISA studies, compound 7q efficiently reduced the levels of Gal-1 protein in dose-dependent manner with an IC50 value of 100 μM. The binding constant (Ka) of 7q with Gal-1 was observed as 1.3 × 104 M?1 by fluorescence spectroscopy. The molecular docking studies clearly showed possible interactions and the pharmacokinetic (ADMET) properties of compound 7q with Gal-1. Hence, the novel 4, 7-disubstituted coumarins could be a potential cytotoxic and PET imaging agents via Gal-1.

β-Cyclodextrin included coumarin derivatives as selective fluorescent sensors for Cu2+ ions in HeLa cells

A highly sensitive and selective fluorescent sensor for Cu2+ ions in water medium is reported using 4-((benzo[d]thiazol-2-ylthio)methyl)-5,7-dihydroxy-2H-chromen-2-one (1) included β-cyclodextrin, as a probe. The fluorogenic supramolecule has displayed good selectivity and affinity towards Cu2+ ions over other cations after examining in biological systems with intracellular Cu2+ ions, especially in cultured HeLa cells using fluorescence microscopic imaging. The lowest detection limit of Cu2+ ions observed using this probe is as low as 2.52 × 10-10 M. The observed on-off fluorescence with the periodic addition of Cu2+ ion is explained via an Intramolecular Charge Transfer mechanism (ICT) and the inclusion of 1 in β-cyclodextrin is characterised by 1H-NMR molecular modeling studies. The results show that the present β-CD:1 system, studied in HeLa cells, can be potentially used in monitoring the biological functions of Cu2+ ions.

B(C6F5)3-catalyzed synthesis of coumarins via Pechmann condensation under solvent-free conditions

Tris(pentafluorophenyl)borane [B(C6F5)3] catalyzed simple, efficient and environmentally benign protocol has been developed for the Pechmann condensation using variety of phenols and β-ketoesters under solvent-free conditions to afford coumarin derivatives. The present protocol displayed significant advantages such as low catalyst loading, short reaction time, mild reaction conditions, low toxicity, easy work-up, high yields, and compatibility with other functional groups. In addition, it is a convenient, clean, and fast alternative approach for synthesizing variety of coumarin derivatives. Moreover, the applicability of this method towards large-scale synthesis demonstrated its suitability for the industrial application. Graphic abstract: [Figure not available: see fulltext.]

Synthesis of C4-substituted coumarins via Pechmann condensation catalyzed by sulfamic acid. Insights into the reaction mechanism by HRMS analysis

A series of functionalized C4-substituted coumarins were synthesized by exploring the reaction of activated and non-activated phenols and β-ketoesters under solvent-free conditions in the presence of sulfamic acid as a Br?nsted acid catalyst. Fifteen exam