3385-03-3 Usage
Chemical Properties
White Solid
Originator
Syntaris,Syntex,UK,1978
Uses
Synthetic fluorinated corticosteroid related to Prednisolone (P703740). Antiasthmatic.
Manufacturing Process
(a) Preparation of 6α-fluoro-16α-hydroxyprednisolone: 1.9 liters of whole
mash containing 400 mg of 6α-fluoroprednisolone (6α-fluoro-11β,17α,21-
trihydroxy-1,4-pregnadiene-3,20-dione) acted upon by Streptomyces
roseochromogenus AE-751 (or Waksman No. 3689) is filtered and the filtrate
extracted three times with 2 liter portions of ethyl acetate. The mycelium is
extracted with 500 ml of ethyl acetate and the mixture filtered. The combined
ethyl acetate extracts are washed with 200 ml of water and concentrated to a
residue. The residue is subjected to partition chromatograph using a 200 g
column of diatomaceous earth moistened with the lower phase of an
equilibrated solvent system composed of 1 volume of water, 5 volumes of
dioxane, and 3 volumes of cyclohexane. The upper phase is used to develop the column and the activity of the eluent is followed by measuring the
ultraviolet absorbance at 240 mμ. The cuts containing most of the activity are
concentrated to a syrupy residue and triturated with acetone. Crystals (25
mg) form and recrystallization gives a product with a MP of 226°C to 230°C.(b) Preparation of 16α,17α-isopropylidenedioxy-6α-fluoro-1,4-pregnadiene-
11β,21-diol-3,20-dione: 15 mg of crystalline 6α-fluoro-11β,16α,17α,21-
tetrahydroxy-1,4-pregnadiene-3,20-dione [6α-fluoro-16α-hydroxyprednisolone
described in US Patent 2,838,546 and prepared as described in (a) above] is
dissolved in 2 ml of acetone and 0.02 ml of 70% perchloric acid is added. The
solution is allowed to stand 1 hour. Then 0.5 ml of saturated sodium
bicarbonate solution is added and the solution concentrated under reduced
pressure to about 1 ml. The solution is allowed to stand overnight and the
crystals which form are filtered, washed with ether and recrystallized from
acetone-hexane. The crystals are the 16α,17α-isopropylidene derivative of 6α-
fluoro-16α-hydroxyprednisolone.
Brand name
Aerobid (Roche); Aerospan Hfa (Forest); Nasalide (IVAX); Nasarel (IVAX).
Therapeutic Function
Antiinflammatory
General Description
The portion of a flunisolide (AeroBid,Nasarel) dose that is swallowed is rapidly converted to the6β-hydroxy metabolite after first-pass metabolism in theliver. The 6β-hydroxy metabolite is approximately as activeas hydrocortisone itself, but the small amount produced usuallyhas limited systemic effects. Water-soluble conjugatesare inactive.
Clinical Use
Flunisolide is an acetone ketal (acetonide) with a 6α-fluoro group and a free C-21 hydroxyl
group. The acetonide decreases mineralocorticoid activity, and the 6α-fluoro group increases
glucocorticoid activity. It is not a prodrug, because it has the free hydroxyl group at C-21.
Flunisolide has approximately 20% of the receptor affinity as budesonide, and approximately 40%
of the inhaled dose is systemically bioavailable.
Metabolism
When administered intranasally or by inhalation, flunisolide is rapidly absorbed
from nasal or lung tissue(94). This corticosteroid is efficiently metabolized by the liver to inactive
metabolites with no apparent effects on adrenal function with long-term therapy. Flunisolide that is swallowed undergoes extensive first-pass metabolism in the liver, and that which is absorbed directly from the
nasopharyngeal mucosa or lung bypasses this initial metabolism. It is not known if the drug undergoes
metabolism in the GI tract.
Flunisolide is rapidly hydroxylated by CYP3A4 at the 6β position, followed by
elimination of the 6α-fluoro group to its more polar 6β-hydroxy metabolite, which attains plasma concentrations
that usually are greater than those for flunisolide.
Check Digit Verification of cas no
The CAS Registry Mumber 3385-03-3 includes 7 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 4 digits, 3,3,8 and 5 respectively; the second part has 2 digits, 0 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 3385-03:
(6*3)+(5*3)+(4*8)+(3*5)+(2*0)+(1*3)=83
83 % 10 = 3
So 3385-03-3 is a valid CAS Registry Number.
InChI:InChI=1/2C24H31FO6.H2O/c2*1-21(2)30-19-9-14-13-8-16(25)15-7-12(27)5-6-22(15,3)20(13)17(28)10-23(14,4)24(19,31-21)18(29)11-26;/h2*5-7,13-14,16-17,19-20,26,28H,8-11H2,1-4H3;1H2/t2*13-,14-,16-,17-,19+,20+,22-,23-,24+;/m00./s1
3385-03-3Relevant articles and documents
NOVEL PROCESS FOR PREPARATION OF CORTICOSTEROIDS
-
, (2018/03/25)
The present invention discloses a process for the preparation of pregnadiene derivatives having formula I, their stereoisomer and intermediate thereof. Formula I wherein each substituent is independently, R1 and R2 is hydrogen or C1 –C8straight, branched alkyl chain, saturated or unsaturated cycloalkyl; R3 is hydrogen or wherein R5 represents C1-C8 straight, branched alkyl chain or cycloalkyl; R4 is hydrogen or halogen; R6 is hydrogen or halogen;
Method for reducing or preventing transplant rejection in the eye and intraocular implants for use therefor
-
, (2008/06/13)
Methods for reducing or preventing transplant rejection in the eye of an individual are described, comprising: a) performing an ocular transplant procedure; and b) implanting in the eye a bioerodible drug delivery system comprising an immunosuppressive agent and a bioerodible polymer.
Suspension aerosol formulations of pharmaceutical products
-
, (2008/06/13)
Pharmaceutical preparations for producing powder aerosols using propellant gases which use TG 227, and possibly also TG 11, TG 12, TGH 114, propane, butane, pentane or DME.
