Fluticasone furoate

Base Information

• Chemical Name: Fluticasone furoate
• CAS No.: 397864-44-7
• Molecular Formula: C27H29 F3 O6 S
• Molecular Weight: 538.585
• European Community (EC) Number: 629-894-6
• UNII: JS86977WNV
• DSSTox Substance ID: DTXSID401024827
• Nikkaji Number: J2.515.103H
• Wikipedia: Fluticasone_furoate
• Wikidata: Q2166700
• NCI Thesaurus Code: C77003
• RXCUI: 705022
• Pharos Ligand ID: 1DR8DSQNL55C
• Metabolomics Workbench ID: 151992
• ChEMBL ID: CHEMBL1676
• Mol file: 397864-44-7.mol

Synonyms:fluticasone furoate

Chemical Property of Fluticasone furoate

Chemical Property:

• Boiling Point: 625.2±55.0 °C(Predicted)
• PKA: 12.52±0.70(Predicted)
• PSA: 119.11000
• Density: 1.39
• LogP: 4.92680
• Storage Temp.: -20°C Freezer
• Solubility.: Chloroform (Slightly, Heated, Sonicated), Methanol (Slightly)
• XLogP3: 4.8
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 10
• Rotatable Bond Count: 6
• Exact Mass: 538.16369430
• Heavy Atom Count: 37
• Complexity: 1080

Purity/Quality:

99%, ^*data from raw suppliers

FluticasoneFuroate ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1CC2C3CC(C4=CC(=O)C=CC4(C3(C(CC2(C1(C(=O)SCF)OC(=O)C5=CC=CO5)C)O)F)C)F
• Isomeric SMILES: C[C@@H]1C[C@H]2[C@@H]3C[C@@H](C4=CC(=O)C=C[C@@]4([C@]3([C@H](C[C@@]2([C@]1(C(=O)SCF)OC(=O)C5=CC=CO5)C)O)F)C)F
• Recent ClinicalTrials: Medical vs Surgical Treatment in OSA Among Children
• Recent EU Clinical Trials: A phase IV, open label, multicentre, randomised, 2-way cross-over exploratory clinical trial comparing a fixed combination of beclometasone dipropionate plus formoterol fumarate plus glycopyrronium administered via pMDI (TRIMBOW?) and a fixed combination of fluticasone furoate plus vilanterol administered via DPI (RELVAR? ELLIPTA?) on lung stiffness reduction assessed through area under the reactance curve (AX) using forced oscillation technique (FOT) in patients with chronic obstructive pulmonary disease (COPD).
• Recent NIPH Clinical Trials: The efficacy of high-dose ICS / LABA or medium-dose inhaled ICS / LABA / LAMA in patients with poor asthma control under medium-dose ICS / LABA administration
• Description: Fluticasone furoate is a new corticosteroid derivative launched as a nasal spray for the treatment of seasonal and perennial allergic rhinitis in adults and in children aged ≥2 years. It is structurally closely related to the previously marketed intranasal corticosteroid fluticasone propionate (FP). Both of these steroids contain the unusual S-fluoromethyl carbothioate group, which confers high lipophilicity and hence enhanced binding and retention of the drug by the nasal tissue. Additionally, the carbothioate group rapidly undergoes first-pass metabolism by CYP3A4, thus minimizing systemic exposure of the parent drug. Fluticasone furoate is a potent ligand for the glucocorticoid receptor (GR), with a relative receptor affinity (RRA) of 2,989 with reference to dexamethasone RRA of 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. 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.
• Uses: It is one of the newest A synthetic corticosteroid 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.

Technology Process of Fluticasone furoate

There total 19 articles about Fluticasone furoate which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 99.3%

6α,9α-difluoro-17α-(furan-2-yl)carbonyloxy-11β-hydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carbothioic acid (397864-40-3) + bromofluoromethane (373-52-4) → fluticasone furoate (397864-44-7)

Guidance literature:

In butanone; at 0 - 22 ℃;

Reference yield: 82.0%

→ fluticasone furoate (397864-44-7)

Guidance literature:

Reference yield:

C29H28F6O7S (1414857-60-5) → fluticasone furoate (397864-44-7)

Guidance literature:

With methanol; ammonia; at 0 ℃; for 0.0833333h;

upstream raw materials:

6α,9α-difluoro-17α-(furan-2-yl)carbonyloxy-11β-hydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carbothioic acid

bromofluoromethane

N-(monofluoromethyl)-N-phenyl-dimethylammonium triflate

S-acetic acid-6a,9a-difluoro-17a-[(2-furanyicarbonyl)oxy]-11-hydroxy-16a-methyl-3-oxo-androsta-1,4-diene-17-(3-carbothiate)

Refernces

• 1、 -. "A method for preparing pyromucic acid fluorine for kasong (by machine translation)". Paragraph 0047; 0048. . Retrieved 2019/10/22.
• 2、 -. "PROCESS FOR PREPARING FLUTICASONE PROPIONATE/FUROATE". Paragraph 0066. . Retrieved 2014/06/11.