397864-44-7

Usage

Uses

Used in Pharmaceutical Industry:
Fluticasone furoate is used as an anti-inflammatory agent for the treatment of seasonal allergic rhinitis. Its high receptor affinity and lipophilicity contribute to its effectiveness in reducing inflammation and alleviating symptoms associated with allergic rhinitis.
Used in Respiratory Treatment:
Fluticasone furoate is used as a corticosteroid in combination with vilanterol trifenate for the treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD). Its potent anti-inflammatory properties help in managing COPD symptoms and improving lung function.
Used in Allergy Treatment:
Fluticasone furoate is used as a nasal spray for the treatment of perennial allergic rhinitis, providing relief from nasal symptoms such as sneezing, itching, and congestion.
Used in Nasal Polyp Treatment:
Fluticasone furoate is used in reducing inflammation in patient-derived nasal polyp tissue, decreasing the levels of various inflammatory cytokines, such as IFN-γ, IL-2, IL-5, IL-17, and TNF-α.
Used in Allergic Inflammation Treatment:
Fluticasone furoate is used in reducing eosinophil infiltration in bronchoalveolar lavage fluid (BALF) in a rat model of allergic inflammation, demonstrating its potential in treating allergic conditions.

Synthesis

The synthesis of fluticasone on large scale was disclosed in the patent literature. The starting 6α ,9α- difluoro-11β-17α-dihydroxy-16α-methyl-3-oxoandrosta-1,4- diene-17β-carboxylic acid 35 was converted to the analogous carbothioic acid 36 in 95% yield via activation with carbonyl diimidazole, followed by reaction with hydrogen sulfide gas. Conversion of the carbothioic acid to fluticasone was completed through a three-step sequence in a one pot process in 99% overall yield. Carbothioic acid 36 and DMAP were dissolved in MEK. Tripropylamine (TPA) was then added to the mixture at -8 to -5°C. Neat furoyl chloride was then added dropwise over 2-3 minutes and the resulting mixture was then stirred at -5 to 0°C for 15 minutes generating a mixture of desired ester 37 and thioanhydride 38. A solution of N-methylpiperazine in water was then added dropwise over 2-3 minutes at -5 to 0°C to the crude reaction mixture and stirred for 10 minutes, which enabled the conversion of thioanhydride 38 to the ester 37. A solution of bromofluoromethane in MEK was then added rapidly at 0°C and the resulting solution was stirred at 20°C for 5 hours. After a simple work-up, fluticasone furoate (V) was obtained in 99% overall yield from 36 with 97% purity.

Upstream product

• 373-52-4 bromofluoromethane 
• 397864-41-4 (1R,2S,8S,10S,11S,13R,14R,15S,17S)-1,8-difluoro-14-{[(furan-2-yl)carbonylsulfanyl]carbonyl}-17-hydroxy-2,13,15-trimethyl-5-oxotetracyclo[8.7.0.02,7.011,15]heptadeca-3,6-dien-14-yl furan-2-carboxylate 
• 80473-92-3 6α,9α-difluoro-11β,17α-dihydroxy-16α-methyl-3-oxo-androsta-1,4-diene-17β-carbothioic acid 
• 28416-82-2 6α,9α-difluoro-11β,17α-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid 
• 948565-92-2 6α,9α-difluoro-17α-[(2-furylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxoandrost-1,4-dien-17β-thiocarboxylic acid S-N,N-dimethylcarbamoyl ester 
• 2135-17-3 flumetasone 
• 1414857-59-2 C₃₀H₂₉F₅O₉S 
• 397864-40-3 6α,9α-difluoro-17α-(furan-2-yl)carbonyloxy-11β-hydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carbothioic acid 
• 373-53-5 fluoroiodomethane 
• 593-70-4 R₃₂ 
• 1414857-60-5 C₂₉H₂₈F₆O₇S 
• 1414857-58-1 C₃₄H₃₇F₅O₉S 
• 1414857-57-0 C₃₂H₃₈F₂O₈S 
• 1351451-83-6 S-acetic acid-6a,9a-difluoro-17a-[(2-furanyicarbonyl)oxy]-11-hydroxy-16a-methyl-3-oxo-androsta-1,4-diene-17-(3-carbothiate) 

Relevant academic research and scientific papers

X-ray crystal structure of the novel enhanced-affinity glucocorticoid agonist fluticasone furoate in the glucocorticoid receptor-ligand binding domain

An X-ray crystal structure is reported for the novel enhanced-affinity glucocorticoid agonist fluticasone furoate (FF) in the ligand binding domain of the glucocorticoid receptor. Comparison of this structure with those of dexamethasone and fluticasone pr

A method for preparing pyromucic acid fluorine for kasong (by machine translation)

The present invention provides a method for preparing pyromucic acid fluorine for kasong, comprises the following steps: 1) compound VIII in alkali and alcohol solvent in the presence of a hydrolysis to obtain compound II; 2) compound II in reductive salt as catalyst under the condition be, pyromucic acid fluorine for kasong fluorine halogen reaction with methane (compound I). The present invention in order to have the reducing inorganic salt as a catalyst, greatly reducing disulfide impurity, mercapto oxide impurity, and mercapto oxide introduced [...] formation of impurities. (by machine translation)

Preparation method of fluticasone furoate

The invention relates to a preparation method of fluticasone furoate, especially preparation and purification of an intermediate 6alpha, 9alpha-difluoro-17alpha-[(2-furylcarbonyl)oxy]-11beta-hydroxy-16alpha-methyl-3-oxo-androstane-1,4-diene-17beta-thiocarboxylic acid. The preparation method comprises the following steps: in the presence of alkali and alcoholic solvent, a compound as shown in the formula VIII is converted into a mixture containing the compound of formula II; the mixture containing the compound of formula II is mixed with an aqueous solution of inorganic base and an ester solvent; a water phase is separated; pH value of the water phase is regulated by the use of acid until a solid is precipitated out; and the solid is separated. The invention provides a preparation method capable of remarkably raising purity of fluticasone furoate. Safety of drug application is guaranteed.

PROCESS FOR PREPARING FLUTICASONE PROPIONATE/FUROATE

The present invention relates to an improved process for the preparation of substituted Fluticasone derivatives. The invention also reveals the processes for the purification of Fluticasones and related intermediates to provide the highly pure product.

Method for the Production of Fluoromethyl Esters of Androstan-17 beta Carboxylic Acids

Described herein are processes for the preparation of monofluoromethylated organic biologically active compounds, starting from protected intermediates and/or reagents to obtain compounds such as fluticasone propionate and fluticasone furoate, in presence of decarboxylating reagents XeF2 and BrF3, or using FCH2SH as a reagent.

METHOD FOR PREPARING FLUTICASONE FUROATE

Method for preparing fluticasone furoate (6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-[(2-furoyl)oxy]-3-oxo-androsta-1,4-diene-17β-carbothioic acid S-fluoromethyl ester) by directly subjecting a compound of Formula III and a complex of a fluoromethylating reagent in presence of an organic base to a replacement reaction to obtain the target compound. Generation of impurities in a process via Compound IV is avoided; the method is simple with mild reaction conditions, suitable for industrial production, and yields products with purity of 98% by HPLC.

METHOD FOR THE PRODUCTION OF FLUOROMETHYL - ESTERS OF ANDROSTAN- 17 - BETA - CARBOXYLIC ACIDS

The present invention relates to a method of preparing an organic biologically active compound of formula (I), wherein R1, R2, R3, R4,. X1, X2 and X3 are as defined in the specification, to certain novel intermediates obtainable from such a method and their use.

METHODS AND COMPOUNDS FOR THE PREPARATION OF MONOFLUOROMETHYLATED BIOLOGICALLY ACTIVE ORGANIC COMPOUNDS

The present invention describes processes for the preparation of, monofluoromethylated organic biologically active compounds, such as Fluticasone Propionate and Fluticasone Furoate, in the presence of fluorodecarboxylating reagents such as XeF2 and BrF3.

METHOD FOR MONOFLUOROMETHYLATION OF ORGANIC SUBSTRATES TO PREPARE BIOLOGICALLY ACTIVE ORGANIC COMPOUNDS

The present invention describes a process for the preparation of monofluoromethylated organic biologically active compounds using monofluoromethylated reagents. Fluticasone Propionate and Fluticasone Furoate can be prepared using, for example, S-monofluoromethyl-S-phenyl-2,3,4,5- tetramethylphenylsulfonium tetrafluoroborate as monofluoromethylating reagent instead of bromofluoromethane.

POLYMORPHS OF FLUTICASONE FUROATE AND PROCESS FOR PREPARATION THEREOF

Provided are polymorphs of fluticasone furoate and processes for preparation thereof.