2-[(1R,2S,8S,10S,11S,13R,14R,15S,17S)-1,8-difluoro-14,17-dihydroxy-2,13,15-trimethyl-5-oxotetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-3,6-dien-14-yl]-2-oxoethyl 2,2-dimethylpropanoate

• ChemBase ID: 545
• Molecular Formular: C27H36F2O6
• Molecular Mass: 494.5679464
• Monoisotopic Mass: 494.24799531
• SMILES: F[C@@]12[C@H]([C@H]3[C@@]([C@](O)([C@@H](C3)C)C(=O)COC(=O)C(C)(C)C)(C[C@@H]1O)C)C[C@H](F)C1=CC(=O)C=C[C@]21C
• Canonical SMILES: O=C1C=C[C@]2(C(=C1)[C@@H](F)C[C@@H]1[C@]2(F)[C@@H](O)C[C@]2([C@H]1C[C@H]([C@]2(O)C(=O)COC(=O)C(C)(C)C)C)C)C
• InChI: InChI=1S/C27H36F2O6/c1-14-9-16-17-11-19(28)18-10-15(30)7-8-24(18,5)26(17,29)20(31)12-25(16,6)27(14,34)21(32)13-35-22(33)23(2,3)4/h7-8,10,14,16-17,19-20,31,34H,9,11-13H2,1-6H3/t14-,16+,17+,19+,20+,24+,25+,26+,27+/m1/s1
• InChIKey: JWRMHDSINXPDHB-OJAGFMMFSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-[(1R,2S,8S,10S,11S,13R,14R,15S,17S)-1,8-difluoro-14,17-dihydroxy-2,13,15-trimethyl-5-oxotetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-3,6-dien-14-yl]-2-oxoethyl 2,2-dimethylpropanoate; 2-[(1R,2S,8S,10S,11S,13R,14R,15S,17S)-1,8-difluoro-14,17-dihydroxy-2,13,15-trimethyl-5-oxotetracyclo[8.7.0.0^2,^7.0^1^1,^1^5]heptadeca-3,6-dien-14-yl]-2-oxoethyl 2,2-dimethylpropanoate
• IUPAC Traditional name: flumethasone pivalate
• Brand Name: Locorten
• Synonyms: Flumethasone Pivalate; (6α,11β,16α)-21-(2,2-Dimethyl-1-oxopropoxy)-6,9-difluoro-11,17-dihydroxy-16-methyl-pregna-1,4-diene-3,20-dione; Flumetasone Pivalate; Locacorten; Locorten; Lorinden; Losalen; NSC 107680; Flumethasone 21-Pivalate; 6α,9-Difluoro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione 21-(2,2-dimethylpropionate); Flumethasone pivalate

Database IDs

• CAS Number: 2002-29-1
• EC Number: 217-901-1
• MDL Number: MFCD00079287
• PubChem SID: 160964008; 46505121; 24894735
• PubChem CID: 443980

CALCULATED PROPERTIES

JChem

• Acid pKa: 12.435035
• H Acceptors: 5
• H Donor: 2
• LogD (pH = 5.5): 3.5825121
• LogD (pH = 7.4): 3.5825083
• Log P: 3.5825121
• Molar Refractivity: 125.1702 cm^3
• Polarizability: 48.730103 Å^3
• Polar Surface Area: 100.9 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.21
• LOG S: -4.67
• Solubility (Water): 1.07e-02 g/l

PROPERTIES

Physical Property

• Solubility: 0.392 mg/L
• Hydrophobicity(logP): 2.1

Safety Information

• RTECS: TU3832010
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 40
• Safety Statements: 22-36
• GHS Pictograms: GHS08
• GHS Signal Word: Warning
• GHS Hazard statements: H351
• GHS Precautionary statements: P281
• Personal Protective Equipment: Eyeshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges

DETAILS

DrugBank - DB00663

• Drug Groups: approved
• Description: Flumethasone pivalate is a moderately potent difluorinated corticosteroid ester with anti-inflammatory, antipruritic and vasoconstrictive properties. As it is a privalate salt, its anti-inflammatory action is concentrated at the site of application. This local effect on diseased areas results in a prompt decrease in inflammation, exudation and itching.
• Indication: For the treatment of contact dermatitis, atopic dermatitis, exczema, psoriasis, diaper rash and other skin conditions
• Pharmacology: Flumethasone pivalate is a moderately potent difluorinated corticosteroid ester with anti-inflammatory, antipruritic and vasoconstrictive properties. As it is a privalate salt, its anti-inflammatory action is concentrated at the site of application. This local effect on diseased areas results in a prompt decrease in inflammation, exudation and itching.
• Toxicity: Can lead to signs of irritation such as burning sensation, itching or skin rash at the site of application; hypersensitivity reactions.
• Affected Organisms: Humans and other mammals
• Biotransformation: Primarily hepatic
• Absorption: Minimal if applied topically

Sigma Aldrich - F0891

Application
Flumethasone pivalate is a topical corticosteroid. Prompt decrease in inflammation, exudation and itching is experienced after application. It is a difluorinated corticosteroid ester with anti-inflammatory, antipruritic and vasoconstrictive properties. It is used to study adrenocortical suppression1, plasma transcortin binding, and cutaneous atrophy and telangiectasia2.
Biochem/physiol Actions
Flumethasone is a glucocorticoid receptor agonist. It binds to the nucleus causing a variety of genetic activation and repressions. The anti-inflammatory actions 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.
Flumethasone pivalate is a glucocorticoid receptor agonist used in studies on plasma transcortin binding.

Toronto Research Chemicals - F455015

An anti-inflammatory anti-itching corticosteroid found in topical creams.

REFERENCES

• Fliri, A., et al.: J. Med. Chem., 52, 8038 (2009)
• Hoeller, S., et al.: J. Pharm. Sci., 98, 2686 (2009)
• Gohil, V., et al.: Nat. Biotechnol., 28, 249 (2009)