Introduction：Basic information about FLUTICASONE FUROATE CAS 397864-44-7, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
FLUTICASONE FUROATE Basic information
| Product Name: | FLUTICASONE FUROATE |
| Synonyms: | FLUTICASONE FUROATE;Androsta-1,4-diene-17-carbothioic acid, 6,9-difluoro-17-((2- furanylcarbonyl)oxy)-11-hydroxy-16-methyl-3-oxo-, S-(fluoromethyl) ester, (6alpha,11beta,16alpha,17alpha)-;Gw 685698x;Unii-js86977wnv;Veramyst;(6α,11β,16α,17α)-6,9-Difluoro-17-[(2-furanylcarbonyl)oxy]-11-hydroxy-16-Methyl-3-oxoandrosta-1,4-diene-17-carbothioic Acid S-(FluoroMethyl) Ester;AllerMist;AvaMys |
| CAS: | 397864-44-7 |
| MF: | C27H29F3O6S |
| MW: | 538.58 |
| EINECS: | 222-789-2 |
| Product Categories: | Intermediates & Fine Chemicals;Pharmaceuticals;Steroids |
| Mol File: | 397864-44-7.mol |
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FLUTICASONE FUROATE Chemical Properties
| Melting point | 250-252°C (dec.) |
| Boiling point | 625.2±55.0 °C(Predicted) |
| density | 1.39 |
| storage temp. | -20°C Freezer |
| solubility | Chloroform (Slightly, Heated, Sonicated), Methanol (Slightly) |
| pka | 12.52±0.70(Predicted) |
| form | Solid |
| color | White to Off-White |
| InChIKey | XTULMSXFIHGYFS-XEVZMEAZNA-N |
| SMILES | [C@]12(C)C=CC(=O)C=C1[C@@H](F)C[C@@]1([H])[C@]3([H])C[C@@H](C)[C@@](C(=O)SCF)(OC(=O)C4=CC=CO4)[C@@]3(C)C[C@H](O)[C@]21F |&1:0,8,11,13,16,18,32,35,37,r| |
Safety Information
| WGK Germany | WGK 3 |
| Storage Class | 11 - Combustible Solids |
| Hazard Classifications | Repr. 2 |
FLUTICASONE FUROATE Usage And Synthesis
| Description | Fluticasone furoate is a new corticosteroid derivative launched as anasal spray for the treatment of seasonal and perennial allergic rhinitis in adultsand in children aged ≥2 years. It is structurally closely related to the previouslymarketed intranasal corticosteroid fluticasone propionate (FP). Both of thesesteroids contain the unusual S-fluoromethyl carbothioate group, which confershigh lipophilicity and hence enhanced binding and retention of the drug by thenasal tissue. Additionally, the carbothioate group rapidly undergoes first-passmetabolism by CYP3A4, thus minimizing systemic exposure of the parent drug.Fluticasone furoate is a potent ligand for the glucocorticoid receptor (GR), witha relative receptor affinity (RRA) of 2,989 with reference to dexamethasone RRAof 100.
Following intranasal administration, most of the dose is eventually swallowed and undergoes incomplete absorption and extensive firstpass metabolism in the liver and gut, resulting in negligible systemic exposure. Pharmacokinetic studies using oral solution dosing and intravenous dosing show that at least 30% of fluticasone furoate is absorbed and then rapidly cleared from plasma. The most common adverse reactions (W1% incidence) included headache, epistatix, sinus and throat pain, nasal ulceration, back pain, pyrexia, and cough. Fluticasone furoate is chemically derived starting from a readily available corticosteroid, 6a,9a-difluoro-11b,17a-dihydroxy-16a-methyl-3-oxoandrosta-1,4-diene-17b-carboxylic acid, by first converting the carboxylic acid group to the corresponding carbothioic acid via activation with carbonyl diimidazole followed by reaction with hydrogen sulfide gas. Subsequently, selective acylation of the 17a-hydroxyl group with 2-furoyl chloride and alkylation of the 17b-carbothioic acid group with bromofluoromethane under basic conditions provides fluticasone furoate. |
| Description | Fluticasone furoate is a synthetic glucocorticoid. It is selective for the glucocorticoid receptor over the mineralocorticoid, progesterone, and androgen receptors in reporter assays (EC50s = 0.03, 23.4, 0.9, and >10,000 nM, respectively), as well as estrogen receptor α (ERα) and ERβ in scintillation proximity assays (EC50s = >10,000 nM for both). Fluticasone furoate reduces LPS-induced increases in TNF-α production in human peripheral blood mononuclear cells (PBMCs) with an EC50 value of 0.12 nM. It decreases S. aureus enterotoxin-induced increases in IFN-γ, IL-2, IL-5, IL-17, and TNF-α levels in patient-derived nasal polyp tissue when used at a concentration of 100 nM. Intrathecal administration of fluticasone furoate (30 μg/animal) reduces ovalbumin-induced increases in bronchoalveolar lavage fluid (BALF) eosinophil infiltration in a rat model of allergic inflammation. Formulations containing fluticasone furoate have been used in the treatment of seasonal allergies. |
| Chemical Properties | White to Off-White Solid |
| Originator | GSK (US) |
| Uses | It is one of the newest |
| Uses | Fluticasone-d3 Furoate is an isotope labelled form of Fluticasone Furoate (F599510). Fluticasone Furoate is a synthetic corticosteroid derived from fluticasone for treatment of seasonal allergic rhinitis. |
| Definition | ChEBI: 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 2-furoyl sbstituent at position 17. Used in combination with vilanterol trifenate for treatment of bronchospasm associated with chronic obstructive pulmonary disease. |
| Brand name | Veramyst |
| Synthesis | The synthesis of fluticasone on large scale wasdisclosed in the patent literature. The starting 6|á ,9|á-difluoro-11|?-17|á-dihydroxy-16|á-methyl-3-oxoandrosta-1,4-diene-17|?-carboxylic acid 35 was converted to theanalogous carbothioic acid 36 in 95% yield via activationwith carbonyl diimidazole, followed by reaction with hydrogensulfide gas. Conversion of the carbothioicacid to fluticasone was completed through a three-step sequencein a one pot process in 99% overall yield. Carbothioicacid 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 minutesand the resulting mixture was then stirred at -5 to 0??Cfor 15 minutes generating a mixture of desired ester 37 andthioanhydride 38. A solution of N-methylpiperazine in waterwas then added dropwise over 2-3 minutes at -5 to 0??C to the crude reaction mixture and stirred for 10 minutes, whichenabled the conversion of thioanhydride 38 to the ester 37. Asolution of bromofluoromethane in MEK was then addedrapidly at 0??C and the resulting solution was stirred at 20??Cfor 5 hours. After a simple work-up, fluticasone furoate (V)was obtained in 99% overall yield from 36 with 97% purity. |
| References | [1] MARK SALTER. Pharmacological properties of the enhanced-affinity glucocorticoid fluticasone furoate in vitro and in an in vivo model of respiratory inflammatory disease.[J]. American journal of physiology. Lung cellular and molecular physiology, 2007, 293 3: L660-7. DOI: 10.1152/ajplung.00108.2007
[2] NAN ZHANG. Suppression of cytokine release by fluticasone furoate vs. mometasone furoate in human nasal tissue ex-vivo.[J]. PLoS ONE, 2014: e93754. DOI: 10.1371/journal.pone.0093754 |
FLUTICASONE FUROATE Preparation Products And Raw materials
