117-37-3

Usage

Uses

Used in Pharmaceutical Industry:
2-P-ANISYL-1,3-INDANDIONE is used as an anticoagulant for preventing the formation of active procoagulation factors and proteins in the liver. It helps in managing and treating blood clotting disorders.
Used in Medical Imaging:
2-P-ANISYL-1,3-INDANDIONE is used as a radiopaque agent in medical imaging, particularly in diagnostic procedures that require the visualization of blood vessels and other internal structures. Its radiopaque properties allow for better contrast and imaging results.

Originator

Miradon,Schering,US,1960

Manufacturing Process

To a hot solution of 20.6 g of sodium in 400 ml of absolute ethanol, there is added a solution of 110 g of phthalide and 110 g of p-methoxybenzaldehyde. A vigorous reaction ensues and one-half of the alcohol is distilled off over a two hour period. Ice and water are added to the red solution and the diluted solution is acidified with hydrochloric acid. The resulting gum solidifies and the aqueous phase is removed by decantation. The crude solid is recrystallized twice from two liters of ethanol yielding 2-(p-methoxyphenyl)-1,3-indandione as pale yellow crystals, MP 155-156°C.

Therapeutic Function

Anticoagulant

Purification Methods

Crystallise anisidinone from acetic acid or EtOH. [Horeau & Jacqius Bull Soc Chim Fr 53 1948, Koelsch J Am Chem. Soc 58 1331 1936, Beilstein 8 III 2931.]

InChI:InChI=1/C16H12O3/c1-19-11-8-6-10(7-9-11)14-15(17)12-4-2-3-5-13(12)16(14)18/h2-9,14H,1H3

Upstream product

• 87-41-2 2-benzofuran-1(3H)-one 
• 123-11-5 4-methoxy-benzaldehyde 
• 4767-61-7 3-(4-methoxybenzylidene)phthalide 
• 64-17-5 ethanol 
• 141-52-6 sodium ethanolate 
• 7434-84-6 3-(4-methoxybenzylidene)isobenzofuran-1(3H)-one 
• 1807-49-4 2-diazo-indan-1,3-dione 
• 100-66-3 methoxybenzene 
• 131-11-3 phthalic acid dimethyl ester 
• 53917-01-4 1-(4-methoxyphenyl)butan-2-one 
• 20604-08-4 3-amino-2-(4-methoxyphenyl)-1-inden-1-one 
• 93-58-3 benzoic acid methyl ester 
• 104-47-2 p-methoxybenzylnitrile 
• 104-01-8 4-Methoxyphenylacetic acid 

Downstream Products

• 92858-68-9 2-Nitro-2-(4-methoxy-phenyl)-indandion-(1,3) 
• 41099-25-6 2,3-bis (4-methoxyphenyl)-1H-inden-1-one 
• 3312-38-7 2-(4-methoxyphenyl)-3-phenyl-1H-inden-1-one 
• 94796-75-5 3-chloro-2-(4-methoxyphenyl)-1-indenone 
• 94796-78-8 3-bromo-2-(4-methoxyphenyl)-1H-inden-1-one 
• 107379-19-1 3-Mercapto-2-(4-methoxy-phenyl)-indene-1-thione 
• 119392-17-5 2-(4-methoxyphenyl)-3-ethylindenone 
• 1217-32-9 2-(4-hydroxyphenyl)-1,3-indandione 
• 7360-89-6 2-(4-anisyl)-2-thiocyanatoindan-1,3-dione 
• 475631-84-6 [2-(4-methoxy-phenyl)-1,3-dioxo-indan-2-yl]-phenyl-acetic acid methyl ester 
• 551929-17-0 (3-methoxy-phenyl)-[2-(4-methoxy-phenyl)-1,3-dioxo-indan-2-yl]-acetic acid methyl ester 
• 551929-13-6 (4-methoxy-phenyl)-[2-(4-methoxy-phenyl)-1,3-dioxo-indan-2-yl]-acetic acid methyl ester 
• 52033-66-6 2-(4-methoxyphenyl)-3-phenyl-1H-indene 
• 119392-18-6 2-(4-methoxyphenyl)-3-ethylindene 

Relevant academic research and scientific papers

INDANONE AND INDANDIONE DERIVATIVES AND HETEROCYCLIC ANALOGS

The invention relates to indanone/indandione derivatives and heterocyclic analogs of Formula (I) wherein Ar1, A, B, L1, Y, Z, and (R1)n n are as described in the description; to pharmaceutically acceptable salts thereof, and to the use of such compounds as medicaments, especially as NPS receptor antagonists.

Synthesis, characterization, antimicrobial activities and QSAR studies of some 10a-phenylbenzo[b]indeno[1,2-e][1,4]thiazin-11(10aH)-ones

A series of 10a-phenylbenzo[b]indeno[1,2-e][1,4]thiazin-11(10aH)-ones (3) has been synthesized and tested for their antimicrobial activity. The antimicrobial evaluation data indicated that compounds, 3b, 3d, 3k and 3m exhibited very promising antibacterial activity and the compounds 3b and 3k exhibited notable activity, almost comparable to penicillin for Staphylococcus aureus and Bacillus subtilis respectively. The derivatives 3g and 3l exhibited high antifungal activity. Moreover, antibacterial activities were more prolific than antifungal activity. The QSAR studies indicated the importance of topological parameters, Kiers second order molecular index (κα 2) and molecular connectivity index (χ) in describing the antibacterial activity and electronic parameters, the energy of highest occupied molecular orbital (HOMO) and the dipole moment (μ) in describing the antifungal activity.

Synthesis of novel indane-1,3-dione derivatives and their biological evaluation as anticoagulant agents

2-Substituted derivatives of indane-1,3-dione 3a-f , 5a-g, 6a-g were synthesized and investigated as anticoagulant agents. 2-Arylindane-1,3-diones (3) were obtained in the reaction of phthalide with appropriate arylaldehydes. 2-Arylmethyleneindane-1,3-diones (5) were prepared by condensation of indane-1,3-dione with the corresponding arylaldehydes. The compounds 5 were converted into their methyl analogues 6 by reduction with sodium tetrahydroborate. All of the compounds studied were screened for the anticoagulant activity. The highest prothrombin time was established for 2-[4-(methylsulfanyl) phenyl]indane-1,3-dione (3c) (PT = 33.71 (± 26.01) s), which was very close to PT of the drug anisindione (PT = 36.0 (± 26.42) s).

Synthesis and pharmacological properties of sulfur derivatives of indane-1,3-dione

Synthesis of sulfur derivatives of indane-1,3-dione, VIIb-c, VIIIa-b, IX and X is described. Results of a preliminary pharmacological screening of six compounds [VIIb, VIII, VIIIb, IX, X and XI] are presented.

Enolate Ions as ss-Activators of ortho-metalation: Direct Synthesis of 3-Aminoindenones

ss-Ketonitriles derived from a Claisen condensation of benzoate esters with alkyl- or phenylacetonitriles lead to 3-aminoindenones in the presence of excess LDA. This new reaction is also applicable to pyridine carboxylic esters. All of the 3-aminoindenones and their aza analogues can be hydrolyzed by acid to give the corresponding 1,3-indandiones. The mechanism of the reaction falls into the directed-ortho-metalation class in which the initial enolate ion of the keto-nitrile directs self-metalation at an ortho position. The new anion then cyclizes onto the nitrile group to generate an aminoindenone. Surprisingly the simplest member of the series, benzoylacetonitrile, does not undergo cyclization. Mechanistic isotope studies revealed that this substance preferentially and directly forms a dianion on the side chain, which is not further deprotonated at the ortho position of the aromatic ring.

A new anionic cyclization reaction: Condensation of benzoate esters with nitriles to give 3-amino-2-inden-1-ones

A new type of anionic cyclization has been discovered in which the condensation of alkyl benzoates with simple nitriles, induced by an excess of LDA, leads directly to substituted-3-amino-1-ones. The corresponding intermediate β-oxonitriles undergo cyclization to give, in most instances, superior yields of the same compounds. Acid hydrolysis of these indenones leads in high yield to the corresponding biologically active (anticoagulant) indandiones.

Rhodium(II) Acetate Catalysed Reactions of 2-Diazo-1,3-indandione and 2-Diazo-1-indanone with Various Substrates

Decomposition of 2-diazo-1,3-indandione (3) by rhodium(II) acetate (1) in cyclohexane and in benzene results in overall carbon-hydrogen insertion to give 2-substituted 1,3-indandiones.Anisole, 1, and 3 yield 2-(4-methoxyphenyl)-1,3-indandione (74 percent); benzenes substituted by a single methyl or halogen groups yield the corresponding ortho- and para-substitution products.Spirocyclopropanes are obtained by rhodium(II)-catalyzed additions of 3 to olefins; electron-deficient olefins do not give adducts.Substituted 4H-indenofuran-4-ones and 2,3-disubstituted spiroindene>-1',3'-diones are formed from rhodium(II)-catalyzed reactions of 3 with acetylenes.Reactions of 1 and 3 with cyclohexane, olefins, acetylenes, and arenes involve selective electrophilic carbenic or ylidic processes. 2-Diazo-1-indanone (4) is converted by 1 to 2,2'-bis (48).Thiophenol reacts with 4 and 1 to yield 2-(phenylthio)-1-indanone (49).Cyclopropanations of cyclohexene and styrene by 4 as catalyzed by 1 result in spiroheptane-7,2'-indan>-1-one (50) and 2-phenylspiroinden>-1'(3'H)-one (51), respectively.

Reactions of Carbonyl Compounds in Basic Solutions. Part 9. Methoxide-catalysed Cyclization of Benzylidenephthalides and Methyl o-Phenylacetylbenzoates

The detailed mechanism of the methoxide-catalysed rearrangement of substituted benzylidenephthalides and both normal and pseudo methyl o-phenylacetylbenzoates to form 2-phenylindane-1,3-diones has been studied.A rate-acidity function correlation for the reactions in methanolic dimethyl sulphoxide (DMSO) shows a linear increase in rate with increasing H- to reach a maximum in rate before decreasing, except for the p-nitro substrate.This derivative shows a rate decrease throughout the H- range.The ρ values in methanol and in 94 mol percent methanolic DMSO are 1.7 and -1.6, respectively.The kinetic isotope effect has been observed with kH/kD 0.8-1.0.The equilibrium constants for ring-chain tautomerism of the methyl o-phenylacetylbenzoates have been determined and shown to be independent of substituent and solvent composition.The rate-determining step is the intramolecular attack of the anion of the normal ester on the ester carbonyl group.In methanol and methanolic DMSO of high methanol content this is preceded by the ionization equilibrium of the normal ester.In methanolic DMSO of low methanol content and for the p-nitro substrate, the initial state is the anion itself.

Hypolipidemic Activity of Indan-1,3-dione Derivatives in Rodents

A series of 2-substituted indan-1,3-dione derivatives, including alkyl (C-1-C-5), mono- and disubstituted phenyl, and other 2-aryl derivatives, were tested for hypolipidemic activity of CF1 male mice at 20 mg/kg per day.These derivatives reduced both serum cholesterol and triglycerides after 16 days of administration intraperitoneally. 2-(4-Methoxyphenyl)indan-1,3-dione was one of the more active compounds with 41percent reduction of serum cholesterol and 58percent reduction of serum triglyceride levels on day 16.This activity was confirmed in the rat after oral administration. 2-(2-Methylphenyl)- and 2-(4-chlorophenyl)indan-1,3-dione were effective in reducing serum triglyceride levels 58percent and 53percent, respectively, in mice.Serum cholesterol on day 16 was effectively reduced 46percent by 2-(2,4-dimethylphenyl)indan-1,3-dione.The indan-1,3-dione derivatives were more effective than clofibrate in lowering lipid levels in mice.A more detailed study on the effects of 2-(4-methoxyphenyl)indan-1,3-dione demonstrated that key enzymes in the de novo synthesis of lipids were inhibited by the drug lowering tissue levels of lipids but raising those in the feces.The alterations in lipid content of rat lipoprotein fractions by the drug appeared favorable.