39079-62-4

Usage

Uses

Used in Pharmaceutical Industry:
Chromone-3-carboxylic acid is used as a key intermediate compound for the synthesis of various pharmaceutical agents. Its antioxidant properties make it a valuable component in the development of drugs targeting a range of health conditions.
Used in Chemical Synthesis:
Chromone-3-carboxylic acid serves as a crucial building block in the preparation of several chemical compounds, including:
1. Chromane-2,4-diones: These compounds are utilized in the development of pharmaceuticals and other chemical products.
2. Chromone-3-carboxamides: These derivatives have potential applications in various industries, including pharmaceuticals and materials science.
3. 5-(2-hydroxyphenyl)isoxazole: CHROMONE-3-CARBOXYLIC ACID finds use in the synthesis of various chemical products and materials.
4. Chromone-2-carboxamides: These compounds are employed in the creation of pharmaceuticals and other specialty chemicals.
5. Chromone-2-carboxamido-3-esters: These esters are used in the synthesis of a variety of chemical products with diverse applications.

Synthesis Reference(s)

Synthetic Communications, 10, p. 889, 1980 DOI: 10.1080/00397918008061846

InChI:InChI=1/C10H6O4/c11-9-6-3-1-2-4-8(6)14-5-7(9)10(12)13/h1-5H,(H,12,13)/p-1

Upstream product

• 113326-76-4 N-methylnitrone 
• 755009-08-6 C₁₂H₁₁NO₃ 
• 50743-17-4 4-oxo-4H-1-benzopyran-3-carbonitrile 
• 35911-93-4 dichloromethanol 
• 17422-74-1 3-Formylchromone 
• 39079-63-5 4-oxo-4H-1-benzopyran-3-carbonyl chloride 
• 118-93-4 o-hydroxyacetophenone 

Downstream Products

• 68723-74-0 2-phenyl-2H-chromeno[4,3-c]pyrazol-3-one 
• 35572-23-7 (E)-1-(2'-hydroxyphenyl)-3-(piperidin-1-yl)prop-2-en-1-one 
• 491-38-3 1-benzopyran-4(4H)-one 
• 86176-44-5 2,3-Dihydro-2-methoxy-4H-1-benzopyran-4-one 
• 65479-04-1 5,5-<3-(2'-hydroxyphenyl)-isoxazolinyl>-hydroxylamine 
• 51751-34-9 4-hydroxycoumarin-3-carboxaldehyde 
• 61348-47-8 5-(2-hydroxyphenyl)isoxazole 
• 1776-08-5 (E)-3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one 
• 35614-54-1 (Z)-1-(2-hydroxyphenyl)-3-(phenylamino)prop-2-en-1-one 
• 51070-05-4 1-Phenyl-<1>benzopyrano<4,3-c>pyrazol-4(1H)-on 
• 160481-28-7 4-Oxo-4H-chromene-3-carboxylic acid (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester 
• 31964-91-7 2-(2-hydroxybenzoyl)-9H-xanthen-9-one 
• 55168-26-8 trans-1-(2-Hydroxybenzoyl)-2-(4-oxo-4H-<1>benzopyran-3-yl)-ethylen 
• 57669-32-6 2,3-dihydro-2-hydroxy-4H-1-benzopyran-4-one 

Relevant academic research and scientific papers

Routes to Spiroacetals derived from Chroman-4-one

Methyl 2-(4'-hydroxybutyl)chromone-3-carboxylate (7) and the derived epoxide (13) undergo spirocyclisation on treatment with iodomethane-potassium carbonate and Lewis acid respectively.

Synthesis and biological evaluation of new bischromone derivatives with antiproliferative activity

The synthesis of new bischromone derivatives (4a-c and 5a-c) as potential anticancer drugs is described. The difference in the reactivity between 4-oxo-4H-chromene-3-carboxylic acid 2 (or its methyl ester 3) and 4-oxo-4H-chromene-3-carbonyl chloride 1 with three different polyamines: 3,3′-diamino-N-methyldipropylamine (a), 1,4-bis(3-aminopropyl)piperazine (b), 4,9-dioxa-1,12-dodecanediamine (c) resulted in the formation of two different groups of products, compounds 4a-c and 5a-c, designed in agreement with the bisintercalators' structural requirements. The transformation of 4-oxo-4H-chromene-3-carboxylic acid into 2H-chromene-2,4(3H)-diones (5) was confirmed by the NMR and XRD experiments. Compounds 4a and 5a were evaluated in vitro in the highly aggressive melanoma cell line A375. An enhanced induction of apoptosis and cell cycle arrest clearly revealed that compound 5a was more potent than 4a. Compound 5a was also more active in diminishing the adhesive potential of melanoma cells. Current studies support the notion that small changes in the three-dimensional structure of molecules might have a substantial impact on their biological activity. New bischromone derivatives resulting in two different product groups (compounds 4a-c and 5a-c) are described as potential anticancer drugs. N,N′-[(Methylimino)dipropane-3,1-diyl]bis(4- oxo-4H-chromene-3-carboxamide) 4a and (3,3′)-3,3′-{(methylimino) bis[propane-3,1-diyliminomethylylidene]}bis(2H-chromene-2,4(3H)-dione) 5a were evaluated in vitro in the highly aggressive melanoma cell line A375, with 5a showing higher potency in the induction of apoptosis and cell cycle arrest. Compound 5a was also more active in diminishing the adhesive potential of melanoma cells. Copyright

Synthesis and biological evaluation of chromone-3-carboxamides

The aim of our study was to synthesize novel chromone-3-carboxamides and to conduct biological evaluations in search for lead compounds for the treatment of a range of debilitating disease states. Corresponding 2-hydroxyacetophenones were subjected to Vilsmeier-Haack formylation to give chromone-3-carbaldehydes, which were subsequently oxidised to give chromone-3-carboxylic acids. Treatment of the carboxylic acids with thionyl chloride resulted in the in situ formation of the corresponding acid chlorides, which were reacted with various amines in the presence of triethylamine to give the corresponding novel chromone-3-carboxamides in good yields. Selected chromone derivatives were then evaluated for their anti-inflammatory, anti-tryponosomal and cytotoxic properties.

Chromone and donepezil hybrids as new multipotent cholinesterase and monoamine oxidase inhibitors for the potential treatment of Alzheimer's disease

A series of chromone and donepezil hybrids were designed, synthesized, and evaluated as multipotent cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors for the potential therapy of Alzheimer's disease (AD). In vitro studies showed that the great majority of these compounds exhibited potent inhibitory activity toward BuChE and AChE and clearly selective inhibition for hMAO-B. In particular, compound 5c presented the most balanced potential for ChE inhibition (BuChE: IC50 = 5.24 μM; AChE: IC50 = 0.37 μM) and hMAO-B selectivity (IC50 = 0.272 μM, SI = 247). Molecular modeling and kinetic studies suggested that 5c was a mixed-type inhibitor, binding simultaneously to peripheral and active sites of AChE. It was also a competitive inhibitor, which occupied the substrate and entrance cavities of MAO-B. Moreover, compound 5c could penetrate the blood-brain barrier (BBB) and showed low toxicity to rat pheochromocytoma (PC12) cells. Altogether, these results indicated that compound 5c might be a hopeful multitarget drug candidate with possible impact on Alzheimer's disease therapy.

Transformations of 4-oxo-4H-chromene-3-carbaldehyde under the action of FE(CO)5

Transformations of 4-oxo-4H-chromene-3-carbaldehyde in the presence of pentacarbonyliron and HMPA in benzene and toluene were studied, and their probable mechanism was proposed. The structure of 3-(4-oxochroman-3-ylmethyl)- 4H-chromen-4-one was determined by spectral methods and X-ray analysis. Pleiades Publishing, Ltd., 2012.

Synthesis and insecticidal activity of chromanone and chromone analogues of diacylhydrazines

Diacylhydrazine derivatives have been identified as one of the most important insect growth regulators. A variety of diacylhydrazine derivatives were designed and synthesized in recent years due to their unique action mechanism, simple structure, and environmental benign character. This paper describes the molecular design, synthesis, and insecticidal activities of a series of chromanone and chromone analogues of diacylhydrazine derivatives. The preliminary bioassay showed that some of the chromanone analogues exhibited good insecticidal activity against Mythima separata at the dosage of 500 mg L-1. The present work demonstrated that replacement of the chroman ring of ANS-118, a commercial insecticide, with chromanone moiety could result in new compounds with high potent insecticidal activity.

Study of differences in the reactivity of alkyl and aryl nitrones derived from 4-oxo-4H-1-benzopyran-3-carboxaldehyde

On hydrolysis with 70% H2SO4, aliphatic nitrones 2a-d produce the corresponding carboxylic acids 4, but aromatic nitrones 2e, f give aldehyde 1. On heating under reflux in dry MeOH, 2a-d rearrange to 3a-d but aromatic nitrones 2e, f

Synthesis of 3-(3-alkyl-5-thioxo-1H-4,5-dihydro-1,2,4-triazol-4-yl) aminocarbonylchromones

A series of 3-(3-alkyl-5-thioxo-1H-4,5-dihydro-1,2,4-triazol-4-yl) aminocarbonylchromones has been prepared by oxidation of 3-formylchromone with Jones' reagent followed by reaction with 3-alkyl-4-amino-4,5-dihydro-1,2,4- triazole-5(1H)-thione in the presence of POCl3. The structures of the compounds were confirmed by IR, LC-MS, and 1H NMR spectra and elemental analyses.

Structure-activity relationships of a novel class of endothelin-A receptor antagonists and discovery of potent and selective receptor antagonist, 2-(benzo[1,3]dioxol-5-yl)-6-isopropyloxy-4- (4-methoxyphenyl)-2H-chromene-3-carboxylic acid (S-1255). 1. Study on structure-activity relationships and basic structure crucial for ETA antagonism

A novel series of endothelin-A (ETA) selective receptor antagonists having a 2H-chromene skeleton are described. A lead compound, 2-(benzo[1,3] dioxol-5-yl)-2H-chromene-3-carboxylic acid (3), was found by modifications of our own angiotensin II antagonist. A structure-activity relationship (SAR) study of 3 reveals that the structural requirements essential for potent and selective ETA receptor binding affinity are the m,p-methylenedioxyphenyl, carboxyl, and isopropoxy groups at the 2-, 3-,and 6-positions, respectively, on the (R)-2H-chromene skeleton. The substituent at the 4-position is also important for improving the activity, and various hydrophobic functional groups of 6-9 ? such as liner, branched, and cyclic aliphatic groups, unsubstituted and substituted aryl groups, and even halogen atoms were acceptable. These results suggest that (R)-2-(benzo[1,3]dioxol-5-yl)-6-isopropoxy-2H-chromene-3-carboxylic acid, formula 108, is the crucial basic structure to be recognized by the ETA receptor. The most potent compound is (R)-48 (S-1255), which binds to the ETA receptor with an IC50 value of 0.19 nM and is 630-fold selective for the ETA receptor than for the ETB receptor. This compound has 55% oral bioavailability in rats. On the basis of the SAR, the roles of each substituent in the receptor binding are discussed.

Kinetics and mechanism of hydrogen peroxide oxidation of chromone-3-carboxaldehydes in aqueous acid and micellar media

Oxidation of chromone-3-carboxaldehyde (CCA) and substituted analogues by H2O2 has been carried out in aqueous acid (HCl and H2SO4) and micellar media. Reaction kinetics indicated order in |CCA| as well as |H2O2| to be unity while it is a fraction (1 > n > O) in |acid|. Reaction rates were found to be faster in the solvents of low-dielectric constant (D). Added salt (KCl or (NH4)2SO4) increased the rate of oxidation marginally. On the basis of observed linearity of Amis plot and marginal positive salt effect, protonated CCA (enol form of CCA, a cation) and H2O2 (neutral molecule) were considered as reactive species in the rate limiting step. Reaction rates were found to be enhanced significantly in anionic and nonionic micellar (sodium dodecylsulfate (SDS) and Triton X-100 (Tx), respectively) media. However, cationic micelles [cetyl trimethyl ammonium bromide (CTAB)| indicated marginal retardation effect. Effect of anionic and cationic micelles has been interpreted in terms of electrostatic interactions, while that of nonionic micelles in terms of hydrophobic interactions. Structure-reactivity correlations have been interpreted by Hammett's equation. Negative "p" (reaction constant) values indicated cationic transition state. 1996 John Wiley &Sons, Inc.