31005-02-4

Basic information

• Product Name: 7-ETHOXYCOUMARIN
• Synonyms: 7-ETHOXY-1-BENZOPYRAN-2-ONE;7-ETHOXY-1-BENZOPYRANE-2-ONE;7-ETHOXYCOUMARIN;ETHOXYCOUMARIN, 7-;2H-1-Benzopyran-2-one, 7-ethoxy-;Coumarin, 7-ethoxy-;Ethylumbelliferone;7-ETHOXYCOUMARIN, 99.5%
• CAS NO: 31005-02-4
• Molecular Formula: C₁₁H₁₀O₃
• Molecular Weight: 190.2
• EINECS: 250-429-4
• Product Categories: Coumarin;Aromatics Compounds;Aromatics;Building block
• Mol File: 31005-02-4.mol

Chemical Properties

• Melting Point: 88-90 °C(lit.)
• Boiling Point: 265.69°C (rough estimate)
• Flash Point: 143.132 °C
• Appearance: Beige crystalline powder
• Density: 1.1803 (rough estimate)
• Vapor Pressure: 6.36E-05mmHg at 25°C
• Refractive Index: 1.4260 (estimate)
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Chloroform (Slightly), Ethanol (Slightly), Methanol (Slightly)
• Water Solubility: Soluble in hot methanol (very faint turbidity), 95% ethanol (50 mg/ml), DMF, and DMSO. Insoluble in water.
• BRN: 146200
• CAS DataBase Reference: 7-ETHOXYCOUMARIN(CAS DataBase Reference)
• NIST Chemistry Reference: 7-ETHOXYCOUMARIN(31005-02-4)
• EPA Substance Registry System: 7-ETHOXYCOUMARIN(31005-02-4)

Safety Data

• Hazard Codes: Xi
• Safety Statements: 22-24/25
• WGK Germany: 3
• F: 8
• TSCA: Yes
• Hazardous Substances Data: 31005-02-4(Hazardous Substances Data)

Usage

Uses

Used in Enzyme Activity Assays:
7-Ethoxycoumarin serves as a substrate for CYP2B6, an enzyme involved in the metabolism of drugs and other substances. It is utilized in fluorometric assays to measure microsomal monooxygenase activity, which is crucial for understanding enzyme function and drug metabolism.
Used in Metabolism Studies:
In the pharmaceutical and biomedical research industries, 7-Ethoxycoumarin is used as a probe to study metabolism. It is employed in hepatocyte studies, liver perfusion techniques, and cytochrome P450 studies to investigate the metabolic processes and enzyme activities within the liver.
Used in Functional Activity Analysis of Recombinant P450:
7-Ethoxycoumarin is used to assess the functional activity of recombinant cytochrome P450 enzymes, which are engineered versions of naturally occurring enzymes. This helps researchers understand the role of these enzymes in drug metabolism and their potential applications in drug development.
Used as an Internal Standard in HPLC Analysis:
In high-performance liquid chromatography (HPLC) analysis, 7-Ethoxycoumarin is used as an internal standard for in vitro S-warfarin 7-hydroxylation. This allows for accurate quantification and comparison of metabolite levels, ensuring reliable results in drug metabolism and pharmacokinetic studies.

Biochem/physiol Actions

7-Ethoxycoumarin is a cytochrome P450 substrate.

Metabolism

7-Ethoxycoumarin is metabolized by many cytochrome P450 enzymes active in foreign compound metabolism and has been used as a prototypic substrate to monitor P450 (P450) activity in both hepatic and extrahepatic tissues.The in vitro perfusion of the human placental lobule with 7-ethoxycoumarin gives 7-hydroxycoumarin, and perfusion with androstenedione gives the conversion products, estrone, estradiol, and testosterone. The human placenta has only a limited capacity for the metabolism of xenobiotics.Use of 7-Ethoxycoumarin to Monitor Multiple Enzymes in the Human CYP1, CYP2, and CYP3 Families

InChI:InChI=1/C11H10O3/c1-2-13-9-5-3-8-4-6-11(12)14-10(8)7-9/h3-7H,2H2,1H3

Upstream product

• 93-35-6 7-hydroxy-2H-chromen-2-one 
• 75-03-6 ethyl iodide 
• 56-23-5 tetrachloromethane 
• 2032-35-1 Bromoacetaldehyde diethyl acetal 
• 762-21-0 acetylenedicarboxylic acid diethyl ester 
• 74-96-4 ethyl bromide 
• 1261392-51-1 7-ethoxythiocoumarin 

Downstream Products

• 423736-06-5 2,4-diethoxy-cinnamic acid 
• 93-35-6 7-hydroxy-2H-chromen-2-one 
• 91-64-5 coumarin 
• 108979-94-8 7-ethoxy-4-phenyl-2H-chromen-2-one 
• 87-05-8 4-methyl-7-ethoxycoumarin 
• 1261392-51-1 7-ethoxythiocoumarin 

Relevant articles and documents

N-Methylimidazole-mediated synthesis of aryl alkyl ethers under microwave irradiation and solvent free conditions

A microwave-assisted three-component reaction was established for the synthesis of aryl alkyl ethers. The reaction was performed under solvent-free conditions in the presence of N-methylimidazole and dialkyl acetylene-dicarboxylate to furnish a novel approach to O-alkylation of phenol derivatives in high yield.

Design, synthesis and biological evaluation of O-alkyl umbelliferone derivatives as pancreatic lipase inhibitors

A series of coumarin derivatives were synthesised through O-alkylation of umbelliferone. These derivatives were screened for their pancreatic lipase (PL) inhibitory potential. The PL inhibitory effect of compounds with various benzyl and long chain alkyl substituents on umbelliferone were analysed. The compound 1g, having the geranyl substituent was found to have better PL inhibitory potential with an IC50 of 21.64 M. The compounds 1a-j were subjected to molecular docking into the crystal structure of human PL. The molecular docking results are in correlation with the in vitro PL inhibition activity, wherein compound 1g showed a higher MolDock score of -122.12 kcal/mol. The long chain alkyl groups were found to have PL inhibition due to additional interactions with lid domain amino acids (Phe215, Tyr114, Phe77), as revealed by molecular docking study.

Combined molecular modeling and cholinesterase inhibition studies on some natural and semisynthetic O-alkylcoumarin derivatives

Coumarins of synthetic or natural origins are an important chemical class exerting diverse pharmacological activities. In the present study, 26 novel O-alkylcoumarin derivatives were synthesized and have been tested at 100 μM for their in vitro inhibitory potential against acetylcholinesterase (AChE) and butyrlcholinesterase (BChE) targets which are the key enzymes playing role in the pathogenesis of Alzheimer's disease. Among the tested coumarins, none of them could inhibit AChE, whereas 12 of them exerted a marked and selective inhibition against BChE as compared to the reference (galanthamine, IC50 = 46.58 ± 0.91 μM). In fact, 10 of the active coumarins showed higher inhibition (IC50 = 7.01 ± 0.28 μM – 43.31 ± 3.63 μM) than that of galanthamine. The most active ones were revealed to be 7-styryloxycoumarin (IC50 = 7.01 ± 0.28 μM) and 7-isopentenyloxy-4-methylcoumarin (IC50 = 8.18 ± 0.74 μM). In addition to the in vitro tests, MetaCore/MetaDrug binary QSAR models and docking simulations were applied to evaluate the active compounds by ligand-based and target-driven approaches. The predicted pharmacokinetic profiles of the compounds suggested that the compounds reveal lipophilic character and permeate blood brain barrier (BBB) and the ADME models predict higher human serum protein binding percentages (>50%) for the compounds. The calculated docking scores indicated that the coumarins showing remarkable BChE inhibition possessed favorable free binding energies in interacting with the ligand-binding domain of the target. Therefore, our results disclose that O-alkylcoumarins are promising selective inhibitors of cholinesterase enzymes, particularly BChE in our case, which definitely deserve further studies.

Natural and semisynthetic oxyprenylated aromatic compounds as stimulators or inhibitors of melanogenesis

It has been very recently shown how naturally occurring oxyprenylated coumarins are effective modulators of melanogenesis. In this short communication we wish to generalize the potentialities as skin tanning or whitening agents of a wider panel of natural and semisynthetic aromatic compounds, including coumarins, cinnamic and benzoic acids, cinnamaldehydes, benzaldehyde, and anthraquinone derivatives. A total number of 43 compounds have been tested assaying their capacity to inhibit or stimulate melanin biosynthesis in cultured murine Melan A cells. The wider number of chemicals herein under investigation allowed to depict a detailed structure-activity relationship, as the following: (a) benzoic acid derivatives are slightly pigmenting agent, for which the effect is more pronounced in compounds with longer O-side chains; (b) independently from the type of substitution, cinnamic acids are able to increase melanin biosynthesis, while benzaldehydes are able to decrease it; (c) coumarins with a 3,3-dimethylallyl or shorter skeletons as substituents in position 7 are tanning agents, while coumarins with farnesyloxy groups are whitening ones; (d) double oxyprenylation in position 6 and 7 and 3,3-dimethylallyl or geranyl skeletons have slight depigmenting capacities, while farnesyl skeletons tend to marginally increase the tanning effect; (e) the presence of electron withdrawing groups (acetyl, COOH, and -Cl) and geranyl or farnesyl oxyprenylated chains respectively in positions 3 and 7 of the coumarin nucleus lead to a whitening effect, and finally (f) oxyprenylated anthraquinones have only a weak depigmenting capacity.

Peroxy mediated Csp2-Csp3 dehydrogenative coupling: Regioselective functionalization of coumarins and coumarin-3-carboxylic acids

A regioselective direct alkylation of coumarins at C-3 via cross-dehydrogenative coupling of unactivated Csp2-Csp3 bonds is developed. This protocol employs tert-butyl hydroperoxide as the sole reagent of the reaction to combine coumarins and ethers in reasonable yields under metal- and solvent-free reaction conditions. This protocol also worked well with coumarin-3-carboxylic acids to unveil a rare instance of a catalyst-free tandem alkylation/decarboxylation reaction with conservation of the double bond.

Interaction of 7-Alkoxycoumarins with the Aryl Hydrocarbon Receptor

The aryl hydrocarbon receptor (AhR) is a transcription factor activated by a vast array of natural and synthetic ligands. It plays a pivotal role in numerous physiological and pathological responses, such as cell proliferation and differentiation, induction of xenobiotic metabolizing enzymes, response to environmental toxins, and several others. In this study, we investigated the ability of some natural compounds (oxyprenylated ferulic acid and umbelliferone derivatives) and their semisynthetic analogues (e.g., differently substituted 7-Alkoxycoumarins) to activate AhR, using a reporter luciferase assay. Among them, we found that 7-isopentenyloxycoumarin was the best AhR activator. Boropinic acid, 7-but-2′-enyloxycoumarin, 7-(2′,2′-dimethyl-n-propyloxy)coumarin, 7-benzyloxycoumarin, and 7-(3′-hydroxymethyl-3′-methylallyloxy)coumarin were also active, although to a lesser extent. All the compounds were also analyzed for their ability to inhibit AhR activation, using a reference ligand, 6-formylindolo[3,2-b]carbazole. Data recorded in the present investigation pointed out the importance of a 3,3-dimethylallyloxy side chain attached to the coumarin ring core as a key moiety for AhR activation.

Semisynthesis, ex vivo evaluation, and SAR studies of coumarin derivatives as potential antiasthmatic drugs

Asthma is a chronic inflammatory disorder that causes contraction in the smooth muscle of the airway and blocking of airflow. Reversal the contractile process is a strategy for the search of new drugs that could be used for the treatment of asthma. This work reports the semisynthesis, ex vivo relaxing evaluation and SAR studies of a series of 18 coumarins. The results pointed that the ether derivatives 1-3, 7-9 and 13-15 showed the best activity (E max = 100%), where compound 2 (42 μM) was the most potent, being 4-times more active than theophylline (positive control). The ether homologation (methyl, ethyl and propyl) in position 7 or positions 6 and 7 of coumarins lead to relaxing effect, meanwhile formation of esters generated less active compounds than ethers. The SAR analysis showed that it is necessary the presence of two small ether groups and the methyl group at position 4 (site 3) encourage biological activity through soft hydrophobic changes in the molecule, without drastically affecting the cLogP.

Signaling of chloramine: A fluorescent probe for trichloroisocyanuric acid based on deoximation of a coumarin oxime

A new chloramine signaling probe, based on a coumarin oxime, was developed. The coumarin oxime 1 exhibited efficient off-on type fluorescent signaling behavior toward trichloroisocyanuric acid (TCCA) in an aqueous acetonitrile solution. The signaling is due to the TCCA-assisted transformation of the oxime function to its carbonyl analogue. The presence of common metal ions and anions did not interfere with the TCCA signaling of this probe. Probe 1 was found to be useful for the sensitive determination of the concentration of the practical oxidant TCCA in an aqueous environment, with a detection limit of 7.58 × 10-7 M.

Inhibitory effects of 6-alkoxycoumarin and 7-alkoxycoumarin derivatives on lipopolysaccharide/interferon γ-stimulated nitric oxide production in RAW264 cells

Coumarin and its derivatives are well known for their anti-inflammatory and anti-oxidative effects. In this study, we synthesized 32 coumarin derivatives from commercially available 6-hydroxycoumarin (6HC) and 7-hydroxycoumarin (7HC) and examined their ef

Dual signaling of m-chloroperbenzoic acid by desulfurization of thiocoumarin

The chemosignaling of widely used peracid oxidant of m-chloroperbenzoic acid (mCPBA) by the selective desulfurization of thiocoumarin was investigated. Thiocoumarin was efficiently converted into its corresponding coumarin by the reaction with mCPBA, and resulted in a pronounced fluorescent turn-on type signaling. The conversion also provided a significant change in absorption behavior which allowed a ratiometric analysis. The effective signaling could be used as a convenient determination method for mCPBA in aqueous environment.