Flumethasone CAS 2135-17-3

Introduction：Basic information about Flumethasone CAS 2135-17-3, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Flumethasone Basic information

• Product Name: Flumethasone
• Synonyms: 6-alpha,9-alpha-difluoro-11-beta,17-alpha,21-trihydroxy-16-alpha-methylpregna-1,4-diene-3,20-dione;6α,9α-Difluoro-16α-methylprednisolone;6α-Fluorodexamethasone;6a-Fluoro-dexamethasone, Aniprime, Cortexilar, Flucort;Pregna-1,4-diene-3,20-dione, 6,9-difluoro-11,17,21-trihydroxy-16-methyl-, (6.alpha.,11.beta.,16.alpha.)-;6α,9α-difluoro-16α-methyl-11β,17α,21-trihydroxy-1,4-pregnadiene-3,20-dione;FlumethasoneBase98.5%;(6-alpha,11-beta,16-alpha)-6,9-Difluoro-11,17,21-trihydroxy-16-methylpregna-1,4-diene-3,20-dione
• CAS: 2135-17-3
• MF: C22H28F2O5
• MW: 410.45
• EINECS: 218-370-9
• Product Categories: FLUCORT;Hormone Drugs;Intermediates & Fine Chemicals;Pharmaceuticals;Steroids;Steroid and Hormone;2135-17-3
• Mol File: 2135-17-3.mol

Flumethasone Chemical Properties

• Melting point: 237-240°C
• Boiling point: 569.8±50.0 °C(Predicted)
• density: 1.1621 (estimate)
• storage temp.: 2-8°C
• solubility: acetic acid: soluble10mg/mL
• pka: 11.98±0.70(Predicted)
• form: solid
• color: white
• Optical Rotation: [α]25/D 67.0 to 71.0°, c = 1 in dioxane
• Water Solubility: 1mg/L(20 ºC)
• Merck: 14,4138
• InChIKey: WXURHACBFYSXBI-GQKYHHCASA-N
• SMILES: C1(=O)C=C2[C@](C)(C=C1)[C@]1(F)[C@]([H])([C@@]3([H])[C@@](C[C@@H]1O)(C)[C@@](O)(C(=O)CO)[C@H](C)C3)C[C@@H]2F
• CAS DataBase Reference: 2135-17-3(CAS DataBase Reference)

Safety Information

• Hazard Codes: Xn
• Risk Statements: 40
• Safety Statements: 22-36
• WGK Germany: 3
• RTECS: TU3832000
• HS Code: 29144000
• Storage Class: 11 - Combustible Solids
• Hazard Classifications: Carc. 2

Flumethasone Usage And Synthesis

Description

Flumethasone is a moderately potent difluorinated corticosteroid ester with anti-inflammatory, antipruritic and vasoconstrictive properties. Its mechanism of action is thought to inhibit arachidonic acids role in the biosynthesis of prostaglandins and leukotrienes. Flumethasone is active when it is not bound to the plasma protein transcortin. The drug flumethasone can be used to treat a variety of skin conditions, such as contact dermatitis, bug bites and eczema.

Uses

1. Flumethasone is an anti-inflammatory glucocorticoid used in veterinary practice and used as an anti-inflammatory for a variety of animals. It is commonly investigated for its effectiveness in animals to combat inflammatory symptoms caused by pathogens and to better understand inflammatory mechanisms. It is also used as to investigate novel techniques that detect and quantify steroid compounds within muscles.
2. For the treatment of contact dermatitis, atopic dermatitis, exczema, psoriasis, diaper rash and other skin conditions.
3. Flumethasone is a corticosteroid for topical use, in combination with Clioquinol for the treatment of otitis externa and otomycosis. Flumethasone shows fully 420 times the potency of cortisone in an animal model for anti-inflammatory activity.
4. Flumethasone has been shown to exert anti-inflammtory effects by functioning as a glucocorticoid receptor agonist. Stimulating this receptor promotes inhibition of phospholipase A2 activity. This enzyme catalyzes arachidonic acid into eicosanoids most of which stimulate anti-inflammation mechanisms.

Application

1. Flumethasone is a topical corticosteroid of the glucocorticoid class used in the treatment of skin disorders where it reduces inflammation.
2. Flumethasone is insoluble in water.
3. Flumethasone pivalate is a topical difluorinated corticosteroid ester with anti-inflammatory, antipruritic and vasoconstrictive properties. A prompt decrease in inflammation, exudation and itching is experienced after application.
4. It is commonly used in veterinary practice and has been used in cortisol assays to study early porcine conceptus development.

Biological Activity

Flumethasone pivalate is a glucocorticoid receptor agonist used in studies on plasma transcortin binding. It binds to the nucleus causing a variety of genetic activations and repressions. The anti-inflammatory action of flumethasone is thought to involve lipocortins and phospholipase A2 inhibitory proteins, which results in the inhibition of arachidonic acid and the control of prostaglandin and leukotriene biosynthesis. Flumethasone suppresses the immune system due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.

Description

Flumethasone is an agonist of glucocorticoid and mineralocorticoid receptors with EC₅₀ values of 0.26 and 0.494 nM, respectively, in CV-1 cells expressing human receptors. In vitro, it inhibits the growth of UM-UC-3, TCC-SUP, and 5637 urothelial carcinoma cell lines at a concentration of 100 nM. Flumethasone (5 mg per animal) decreases tumor necrosis factor (TNF) production ex vivo in blood cells collected by bronchoalveolar lavage (BAL) from calves with experimentally-induced local lung inflammation. It also inhibits phytohemagglutinin-induced delayed hypersensitivity in calf skin. In vivo, flumethasone (5 μM) impairs cell cycle re-entry of cardiac cells seven days post cryo-injury to the heart and impairs cardiac regeneration in zebrafish.

Chemical Properties

White Solid

Originator

Locacorten,Ciba,W. Germany,1964

Uses

A glucocorticoid. An anti-inflammatory.

Uses

topical anti-inflammatory corticosteroid

Definition

ChEBI: Flumethasone is a fluorinated steroid, a glucocorticoid, an 11beta-hydroxy steroid, a 17alpha-hydroxy steroid, a 21-hydroxy steroid, a 20-oxo steroid, a 3-oxo-Delta(1),Delta(4)-steroid, a primary alpha-hydroxy ketone and a tertiary alpha-hydroxy ketone. It has a role as an anti-inflammatory drug. It derives from a hydride of a pregnane.

Manufacturing Process

To approximately 1.3 g of hydrogen fluoride contained in a polyethylene bottleand maintained at -60°C was added 2.3 ml of tetrahydrofuran and then asolution of 500 mg (0.0012 mol) of 6α-fluoro-9β,11β-epoxy-16α-methyl-17α,21-dihydroxy-1,4-pregnadiene-3,20-dione-21-acetate in 2 ml ofmethylenechloride. The steroid solution was rinsed in with an additional 1 mlof methylene chloride. The light red colored solution was then kept atapproximately -30°C for 1 hour and at -10°C for 2 hours. At the end of this period it was mixed cautiously with an excess of cold sodium bicarbonatesolution and the organic material extracted with the aid of additionalmethylene chloride. The combined extracts were washed with water, driedover anhydrous sodium sulfate and concentrated to approximately 35 ml. Thesolution was chromatographed over 130 g of Florisil anhydrous magnesiumsilicate. The column was developed with 260 ml portions of hexanes(Skellysolve B) containing increasing proportions of acetone. There was thuseluted 6α,9α-difluoro-11β,17α,21-trihydroxy-16α-methyl-1,4-pregnadiene-3,20-dione 21-acetate which was freed of solvent by evaporation of the eluatefractions.

Brand name

Locorten (Novartis).

Therapeutic Function

Glucocorticoid, Antiinflammatory

Veterinary Drugs and Treatments

Flumethasone injection (Flucort?) is labeled in horses as indicatedfor: 1) Musculoskeletal conditions due to inflammation, where permanentstructural changes do not exist, such as bursitis, carpitis,osselets and myositis. Following therapy an appropriate period ofrest should be instituted to allow a more normal return to functionof the affected part. 2) In allergic states such as hives, urticaria andinsect bites.
Flumethasone injection (Flucort?) is labeled in dogs as indicatedfor: 1) Musculoskeletal conditions due to inflammation ofmuscles or joints and accessory structures, where permanent structuralchanges do not exist, such as arthritis, osteoarthritis, the discsyndrome and myositis. In septic arthritis appropriate antibacterialtherapy should be concurrently administered. 2) In certain acuteand chronic dermatoses of varying etiology to help control the pruritus,irritation and inflammation associated with these conditions.The drug has proven useful in otitis externa in conjunction withtopical medication for similar reasons. 3) In allergic states such ashives, urticaria and insect bites. 4) Shock and shock-like states, byintravenous administration.
Flumethasone injection (Flucort?) is labeled in cats as indicatedfor certain acute and chronic dermatoses of varying etiology to helpcontrol the pruritus, irritation and inflammation associated withthese conditions.
Glucocorticoids have been used in an attempt to treat practicallyevery malady that afflicts man or animal, but there are three broaduses and dosage ranges for use of these agents. 1) Replacement ofglucocorticoid activity in patients with adrenal insufficiency, 2) asan antiinflammatory agent, and 3) as an immunosuppressive.Among some of the uses for glucocorticoids include treatment of:endocrine conditions (e.g., adrenal insufficiency), rheumatic diseases(e.g., rheumatoid arthritis), collagen diseases (e.g., systemiclupus), allergic states, respiratory diseases (e.g., asthma), dermatologicdiseases (e.g., pemphigus, allergic dermatoses), hematologicdisorders (e.g., thrombocytopenias, autoimmune hemolytic anemias),neoplasias, nervous system disorders (increased CSF pressure),GI diseases (e.g., ulcerative colitis exacerbations), and renaldiseases (e.g., nephrotic syndrome). Some glucocorticoids are usedtopically in the eye and skin for various conditions or are injectedintra-articularly or intra-lesionally. The above listing is certainlynot complete.

References

[1] CLAUDIA GROSSMANN. Transactivation via the human glucocorticoid and mineralocorticoid receptor by therapeutically used steroids in CV-1 cells: a comparison of their glucocorticoid and mineralocorticoid properties.[J]. European Journal of Endocrinology, 2004, 151 3: 397-406. DOI: 10.1530/eje.0.1510397
[2] HITOSHI ISHIGURO. Differential regulation of bladder cancer growth by various glucocorticoids: corticosterone and prednisone inhibit cell invasion without promoting cell proliferation or reducing cisplatin cytotoxicity.[J]. Cancer Chemotherapy and Pharmacology, 2014, 74 2: 249-255. DOI: 10.1007/s00280-014-2496-7
[3] DARIUSZ BEDNAREK . The effect of steroidal and non-steroidal anti-inflammatory drugs on the cellular immunity of calves with experimentally-induced local lung inflammation[J]. Veterinary immunology and immunopathology, 1999, 71 1: Pages 1-15. DOI: 10.1016/s0165-2427(99)00076-8
[4] ANNE-SOPHIE DE PREUX CHARLES. Distinct effects of inflammation on preconditioning and regeneration of the adult zebrafish heart.[J]. Open Biology, 2016, 6 7. DOI: 10.1098/rsob.160102

Flumethasone Preparation Products And Raw materials

• Raw materials: hydrogen fluoride-->Triamcinolone acetonide 21-acetate-->Hydrogen fluoride
• Preparation Products: (6a,11b,16a)-6,9-Difluoro-11-hydroxy-16-methylandrosta-1,4-diene-3,17-dione-->(6a,11b,16a,17a)-6,9-Difluoro-11,17-dihydroxy-16-methyl-3-oxoandrosta-1,4-diene-17-carboxylic acid-->Fluticasone Impurity