80474-14-2 Usage
Description
Fluticasone propionate is a new glucocorticosteroid useful in the treatment of
seasonal rhinitis and asthma. Compared to beclomethasone dipropionate,
fluticasone propionate is reported to have a comparable side effect profile, but twice
the activity in the treatment of asthma.
Chemical Properties
Fluticasone propionate is a white to off-white powder with a molecular weight of 500.6, and 17 the empirical formula is C25H31F3O5S. It is practically insoluble in water, freely soluble in 18 dimethyl sulfoxide and dimethylformamide, and slightly soluble in methanol and 95% ethanol.
Uses
Different sources of media describe the Uses of 80474-14-2 differently. You can refer to the following data:
1. Fluticasone Propionate is a derivative of Flumethasone, a glucocorticoid. Fluticasone Propionate has antiallergic, anti-asthmatic, and anti-inflammatory properties (1,2,3).
2. Fluticasone propionate, a medium-potency synthetic corticosteroid, is used topically to relieve inflammatory and pruritic symptoms of dermatoses and psoriasis, intranasally to manage symptoms of allergic and non-allergic rhinitis, and orally for the treatment of asthma. Fluticasone Proprionate is marketed under several different brand names such as Flonase(R). Fluticasone propionate is also available as a combination product of Azelastine Hydrochloride and Fluticasone Propionate called Dymista(TM). Dymista(TM) is indicated in patients over 12 years old for symptomatic relief of seasonal allergic rhinitis.
Preparation
Fluticasone propionate, synthesized by Glaxo Wellcome and launched in 1993, is a trifluorinated glucocorticosteroid. It shows good topical antiinflammatory activity and is commonly used as a safe and effective inhaled treatment for asthma and allergic rhinitis.Fluticasone propionate can be synthesized from 9 by using BrCH2F,2a ClCH2F,5a or S-(monofluoromethyl) diarylsulfonium tetrafluoroborate 5f,g directly. Using BrCH2F can get an ideal yield; however, BrCH2F is costly and will destroy to the ozone layer. In addition, 9 reacted with BrCH2Cl or Br2CH2 and then by an anion exchange with AgF,2c,5e KF, or tetrabutylammonium fluoride5b to afford 1 in a low yield.Improved Synthesis of Fluticasone Propionate
Definition
ChEBI: Fluticasone propionate is a trifluorinated corticosteroid that consists of 6alpha,9-difluoro-11beta,17alpha-dihydroxy-17beta-{[(fluoromethyl)sulfanyl]carbonyl}-16-methyl-3-oxoandrosta-1,4-diene bearing a propionyl substituent at position 17; has anti-inflammatory, anti-asthmatic and anti-allergic activity. It has a role as an anti-allergic agent, an anti-asthmatic drug, an anti-inflammatory drug, a dermatologic drug, a bronchodilator agent and an adrenergic agent. It is a corticosteroid, a steroid ester, an 11beta-hydroxy steroid, a propanoate ester, a fluorinated steroid, a thioester and a 3-oxo-Delta(1),Delta(4)-steroid. It derives from a fluticasone. It derives from a hydride of an androstane.
Manufacturing Process
A solution of S-iodomethyl-6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo17α-propionyloxyandrosta-1,4-diene-17β-carbothioate (310 mg) in acetonitrile (10 ml) was stirred with silver fluoride (947 mg) for 3 days at room temperature in the dark. Ethyl acetate (100 ml) was added and the mixture was filtered through kieselguhr. The filtrate was washed successively with 2 N hydrochloric acid, water, saturated brine, then dried. The solvent was removed and the residue was subjected to column chromatography in chloroform then chloroform-acetone (19:1). The product was eluted with ethyl acetate and crystallised on concentration of the solution to give S-fluoromethyl 6α,9αdifluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene17β-carbothioate (0.075 g); melting point 272-273°C (dec.), [α]D= +30° (c 0.35).
Brand name
Cutivate (Altana); Flonase (GlaxoSmithKline); Flovent (GlaxoSmithKline);Flixonase.
Therapeutic Function
Glucocorticoid
General Description
Fluticasone Propionate is the propionate salt form of fluticasone, a synthetic trifluorinated glucocorticoid receptor agonist with antiallergic, antiinflammatory and antipruritic effects. Binding and activation of the glucocorticoid receptor results in the activation of lipocortin that in turn inhibits cytosolic phospholipase A2, which triggers cascade of reactions involved in synthesis of inflammatory mediators, such as prostaglandins and leukotrienes. Secondly, mitogen-activated protein kinase (MAPK) phosphatase 1 is induced, thereby leads to dephosphorylation and inactivation of Jun N-terminal kinase directly inhibiting c-Jun mediated transcription. Finally, transcriptional activity of nuclear factor (NF)-kappa-B is blocked, thereby inhibits the transcription of cyclooxygenase 2, which is essential for prostaglandin production.
Biological Activity
High affinity, selective glucocorticoid receptor agonist (K d = 0.5 nM). Potently stimulates glucocorticoid receptor-mediated transactivation of gene expression and enhances human eosinophil apoptosis (EC 50 = 3.7 nM) in vitro . Inhibits mast cell accumulation in nasal mucosa following topical administration. Lipophilic, clinically-used anti-inflammatory agent with low oral bioavailability.
Biochem/physiol Actions
Fluticasone propionate is a second generation glucocorticoid. Used as an anti-inflammatory agent for asthma. Shown to enhance eosinophil apoptosis in a concentration-dependent manner via the glucocorticoid receptor.
Mechanism of action
Fluticasone propionate has a unique C-20 thioflouromethyl group, and that, in combination with the 17α-propionate ester, gives it 36-fold the glucocorticoid receptor affinity as compared to beclomethasone dipropionate and twofold the affinity as compared to budesonide. The 9α-flouro group increases both glucocorticoid and mineralocorticoid activities, and the 6α-flouro group enhances only the glucocorticoid action. Studies have determined that the effectiveness of inhaled fluticasone propionate results from a local rather than a systemic effect.
Side effects
In controlled US studies, more than 3,300 patients with seasonal allergic, perennial allergic, or perennial nonallergic rhinitis received treatment with intranasal fluticasone propionate. In general, adverse reactions in clinical studies have been primarily associated with irritation of the nasal mucous membranes, and the adverse reactions were reported with approximately the same frequency by patients treated with the vehicle itself. The complaints did not usually interfere with treatment. Less than 2% of patients in clinical trials discontinued because of adverse events; this rate was similar for vehicle placebo and active comparators.Systemic corticosteroid side effects were not reported during controlled clinical studies up to 6 months’ duration with FLONASE Nasal Spray. If recommended doses are exceeded, however, or if individuals are particularly sensitive or taking FLONASE Nasal Spray in conjunction with administration of other corticosteroids, symptoms of hypercorticism, e.g., Cushing syndrome, could occur.PRESCRIBING INFORMATION
Veterinary Drugs and Treatments
While there are topical forms of fluticasone, most veterinary interests
are in the inhaled versions of the drug. The aerosol for pulmonary
inhalation appears to be effective in treating feline asthma, recurrent
airway obstruction (RAO, heaves) or inflammatory airway
disease (IAD) in horses, and dogs with chronic tracheobronchial
disease. While the majority of small animal use has been with fluticasone,
there are several other aerosol corticosteroids for inhalation
(beclomethasone dipropionate, flunisolide, and triamcinolone acetonide)
that theoretically could be used for the same purpose. The
nasal inhalation corticosteroid products may be useful for allergyrelated
chronic rhinosinusitis in cats and dogs.
Metabolism
Interestingly, less than 1% of the swallowed dose is bioavailable, in contrast to the fact that the majority of the inhaled dose is systemically available and highly protein bound. Fluticasone propionate is not a prodrug and is extensively metabolized by the liver. The only detectable metabolite is the 17β-carboxylic acid derived from CYP3A4 oxidation. This metabolite has 2,000-fold less affinity for the glucocorticoid receptor than the parent drug. Elimination is through both the feces and the urine, with the relative amounts determined by the route of administration. Fluticasone propionate is available in aerosol and powder inhalation formulations.
Dosage
Adults: The recommended starting dosage in adults is 2 sprays (50 mcg of fluticasone propionate each) in each nostril once daily (total daily dose, 200 mcg). The same dosage divided into 100 mcg given twice daily (e.g., 8 a.m. and 8 p.m.) is also effective. After the first few days, patients may be able to reduce their dosage to 100 mcg (1 spray in each nostril) once daily for maintenance therapy. Some patients (12 years of age and older) with seasonal allergic rhinitis may find as-needed use of 200 mcg once daily effective for symptom control (see Clinical Trials). Greater symptom control may be achieved with scheduled regular use.
Check Digit Verification of cas no
The CAS Registry Mumber 80474-14-2 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,0,4,7 and 4 respectively; the second part has 2 digits, 1 and 4 respectively.
Calculate Digit Verification of CAS Registry Number 80474-14:
(7*8)+(6*0)+(5*4)+(4*7)+(3*4)+(2*1)+(1*4)=122
122 % 10 = 2
So 80474-14-2 is a valid CAS Registry Number.
InChI:InChI=1/C22H27F3O4S/c1-11-6-13-14-8-16(24)15-7-12(26)4-5-19(15,2)21(14,25)17(27)9-20(13,3)22(11,29)18(28)30-10-23/h4-5,7,11,13-14,16-17,27,29H,6,8-10H2,1-3H3/t11-,13+,14+,16+,17+,19+,20+,21+,22+/m1/s1
80474-14-2Relevant articles and documents
Fluticasone propionate synthesis method
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Page/Page column 7-15, (2020/02/10)
The embodiments of the invention provide a fluticasone propionate synthesis method, which comprises: a thioesterification reaction: adding a first intermediate, an first organic alkali, dimethylaminothioformyl chloride, sodium iodide and a first organic solvent into a reaction kettle, carrying out a reaction, adding a polar aprotic solvent and water after the reaction, carrying out cooling crystallizing, filtering, washing, and drying to obtain a second intermediate; an alcoholysis reaction: adding the second intermediate, a first inorganic alkali and a second organic solvent into a reaction kettle, carrying out a reaction, adding water or water and an extracting agent after the reaction, extracting, taking the water phase, adding hydrochloric acid in a dropwise manner, crystallizing, filtering, washing, and drying to obtain a third intermediate; and a substitution esterification reaction: adding the third intermediate, a second inorganic alkali and a third organic solvent into a reaction kettle, adding fluorobromomethane, adding hydrochloric acid in a dropwise manner, crystallizing, filtering, washing, and drying to obtain fluticasone propionate. According to the embodiments of the invention, the low-cost production can be realized, and the reaction yield and the purity are high.
Preparation method of fluticasone propionate
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, (2019/10/29)
The invention provides a preparation method of fluticasone propionate. The preparation method comprises the following steps that (1) a compound 5 is hydrolyzed in the presence of a base and an alcoholsolvent to obtain a compound 6; and (2) the compound 6 reacts with fluorohalomethane to obtain fluticasone propionate (compound 1) under the condition that a reducing salt is used as a catalyst. According to the preparation method of fluticasone propionate, the reducing inorganic salt is used as the catalyst to greatly reduce the formation of impurities, such as disulfide impurities, sulfhydryl oxide impurities and haloalkylate impurities introduced by sulfhydryl oxides.
PROCESS FOR PREPARING FLUTICASONE PROPIONATE/FUROATE
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, (2014/06/11)
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.
