| Identification | Back Directory | [Name]
Difluprednate | [CAS]
23674-86-4 | [Synonyms]
DFBA
myser
w6309
DUREZOL
CM 9155
Epitopic
DIFLUPREDNATE
Difluprednate-d5
Difluprednate-d3
cetate,17-butyrate
Difluprednate(DFBA)
Difluprednate USP/EP/BP
Difluprednate Solution, 100μg/mL
Difluoroprednisolone butyrate acetate
6α,9-Difluoroprednisolone 21-acetate 17-butyrate
6α,9α-Difluoroprednisolone 21-acetate 17-butyrate
6a,9a-difluoroprednisolone 21-acetate 17-butyrate
6ALPHA,9ALPHA-DIFLUOROPREDNISOLONE 21-ACETATE 17-BUTYRATE
6-alpha,9-alpha-difluoroprednisolone17-butyrate21-acetate
4-diene-3,20-dione,6-alpha,9-difluoro-11-beta,17,21-trihydroxy-pregna-21-a
21-Acetyloxy-6α,9-difluoro-11β-hydroxy-17-(1-oxobutoxy)pregna-1,4-diene-3,20-dione
6a,9-Difluoro-11b,17,21-trihydroxypregna-1,4-diene-3,20-dione 21-acetate 17-butyrate
6a,9-Difluoro-11β,17,21-trihydroxypregna-1,4-diene-3,20-dione 21-Acetate 17-Butyrate
6α,9-Difluoro-11β,17,21-trihydroxypregna-1,4-diene-3,20-dione 21-acetate 17-butyrate
(6α,11β)-21-(Acetyloxy)-6,9-difluoro-11-hydroxy-17-(1-oxobutoxy)pregna-1,4-diene-3,20-dion
(6α,11β)-21-(Acetyloxy)-6,9-difluoro-11-hydroxy-17-(1-oxobutoxy)-pregna-1,4-diene-3,20-dione
(6α,11β)-21-(Acetyloxy)-6,9-difluoro-11-hydroxy-17-(1-oxobutoxy)-pregna-1,4-diene-3,20-dione
Pregna-1,4-diene-3,20-dione, 6α,9-difluoro-11β,17,21-trihydroxy-, 21-acetate 17-butyrate (8CI)
Pregna-1,4-diene-3,20-dione,21-(acetyloxy)-6,9-difluoro-11-hydroxy-17-(1-oxobutoxy)-, (6a,11b)-
Pregna-1,4-diene-3,20-dione, 21-(acetyloxy)-6,9-difluoro-11-hydroxy-17-(1-oxobutoxy)-, (6α,11β)-
Butyric acid, 17-ester with 6α,9-difluoro-11β,17,21-trihydroxypregna-1,4-diene-3,20-dione 21-acetate (8CI) | [EINECS(EC#)]
245-815-4 | [Molecular Formula]
C27H34F2O7 | [MDL Number]
MFCD00214273 | [MOL File]
23674-86-4.mol | [Molecular Weight]
508.55 |
| Questions And Answer | Back Directory | [Preparation]
Difluprednate: 6,9-fluoro-11-hydroxy-4-en-pregn-3,20-dione-17-butyrate-20-acetate. 200 mg of intermediate 8 was added to 5 ml of the solution in a 50 ml polytetrafluoroethylene reaction flask. The mixture was cooled to -25°C, and 2 ml of HF pyridine solution was added. The mixture was stirred and kept at this temperature for 4 hours. The reaction was monitored by TLC until completion. The pH was adjusted to 7.5 with 30% sodium hydroxide solution, followed by acid washing and washing with saturated brine. The DCM layer was separated, dried over anhydrous sodium sulfate, and concentrated to obtain a brownish-yellow oily liquid. Column chromatography yielded 160 mg of a white solid, with a yield of 80% and a purity ≥ 99.0%. |
| Chemical Properties | Back Directory | [Melting point ]
191-194° | [alpha ]
D22 +31.7° (c = 0.5 in dioxane) | [Boiling point ]
600.3±55.0 °C(Predicted) | [density ]
1.1869 (estimate) | [storage temp. ]
2-8°C
| [solubility ]
Dioxane (Slightly), Methanol (Slightly) | [form ]
Solid | [pka]
12.56±0.70(Predicted) | [color ]
White | [InChIKey]
WYQPLTPSGFELIB-ATWWAUKRNA-N | [SMILES]
[C@@]1(OC(=O)CCC)(C(=O)COC(=O)C)CC[C@@]2([H])[C@]3([H])C[C@@H](C4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](O)C[C@]12C)F |&1:0,16,18,21,28,30,32,35,r| |
| Safety Data | Back Directory | [WGK Germany ]
2
| [RTECS ]
TU3831500
| [HS Code ]
2937.29.9095 | [Storage Class]
11 - Combustible Solids | [Toxicity]
mouse,LD50,intraperitoneal,146mg/kg (146mg/kg),BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)BEHAVIORAL: FOOD INTAKE (ANIMAL),Iyakuhin Kenkyu. Study of Medical Supplies. Vol. 15, Pg. 1066, 1984. |
| Hazard Information | Back Directory | [Description]
Difluprednate is a synthetic glucocorticoid that potently activates the glucocorticoid receptor (Ki = 78 pM).1 In vivo, ocular administration of difluprednate (0.05% w/v) increases intraocular pressure in sheep.2 Formulations containing difluprednate have been used to treat diabetic macular edema and inflammation following cataract surgery. | [Chemical Properties]
White Solid | [Originator]
Epitopic,Clin Midy,France,1978 | [Uses]
A corticosteroid (derivative of prednisolone), approved for the treatment of post-operative ocular inflammation. | [Definition]
ChEBI: Difluprednate is a corticosteroid hormone and a butyrate ester. | [Manufacturing Process]
Orthoesterification: A mixture of 1 g of 6α,9α-difluoroprednisolone, 10 mg of
p-toluenesulfonic acid, 5 cc of dimethylformamide and 3 cc of methyl
orthobutyrate is heated for 15 hours on an oil bath at 105°C while a slow
stream of nitrogen is passed through the mixture so that the methanol
produced as a by-product of the reaction, is distilled off. After addition of
several drops of pyridine to neutralize the acid catalyst, the reaction mixture
is evaporated under vacuum and there is obtained a solid residue which is
taken up with methanol, and filtered. The product is recrystallized from a
methylene chloride-methanol mixture to yield 682 mg of 6α,9αdifluoroprednisolone 17α,21-methylorthobutyrate, also identified as 17α,21-
(1'-methoxy)-n-butylidenedioxy-6α,9α-difluoro-δ1,4-pregnadiene-11β-ol-3,20-
dione, MP 194°C-198°C.
Upon chromatography of the mother liquor on a column of alumina another
338 mg of a crystalline mixture of the epimeric orthobutyrates are isolated.
Hydrolysis: A suspension of 1 g of the 6α,9α-difluoroprednisolone 17α,21-
methylorthobutyrate in 10 cc of methanol is treated with 2 cc of a 2 N
aqueous solution of oxalic acid and heated on a water bath at 40°-50°C for
about 5-10 minutes and, afterwards, the mixture is concentrated under
vacuum. The residue is then shaken with water, the insoluble product is
filtered off and then dried. The solid material is recrystallized from acetoneether and 6α,9α-difluoroprednisolone 17-butyrate is obtained, MP 193°-196°C
Esterification: A solution of 500 mg of 6α,9α-difluoroprednisolone-17-butyrate
in 2.5 cc of pyridine is treated with 1.25 cc of acetic anhydride and the
reaction mixture permitted to stand overnight at 0°C. The reaction mixture is
then poured into ice water and the crystalline precipitate formed is filtered off
and recrystallized from a methylene chloride-ether-petroleum ether mixture to
yield 494 mg of 6α,9α-difluoroprednisolone 17-butyrate, 21-acetate; MP 191°-
194°C. | [Therapeutic Function]
Antiinflammatory | [General Description]
Difluprednate, 21-(acetyloxy)-6α,9-difluoro-11β-hydroxy-17-(1-oxobutoxy)pregna-1,4-diene-3,20-dione is being developed (phase III) as a topical ophthalmicemulsion to treat inflammatory eye diseases. | [References]
[1] TETSUYA TAJIKA. Pharmacokinetic features of difluprednate ophthalmic emulsion in rabbits as determined by glucocorticoid receptor-binding bioassay.[J]. Journal of Ocular Pharmacology and Therapeutics, 2011, 27 1: 29-34. DOI: 10.1089/jop.2010.0106
[2] T BORRáS M G S L K Buie. Inducible scAAV2.GRE.MMP1 lowers IOP long-term in a large animal model for steroid-induced glaucoma gene therapy[J]. Gene Therapy, 2016, 23 5: 438-449. DOI: 10.1038/gt.2016.14 |
|
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J & K SCIENTIFIC LTD.
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18210857532 18210857532 |
| Website: |
https://www.jkchemical.com |
| Company Name: |
Sigma-Aldrich
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021-61415566 800-8193336 |
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https://www.sigmaaldrich.cn |
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