1524-88-5

Usage

Uses

Used in Pharmaceutical Industry:
Flurandrenolide is used as an anti-inflammatory agent for its potent glucocorticoid activity, which helps in reducing inflammation and alleviating the symptoms of various skin conditions.
Used in Dermatology:
Flurandrenolide is used as an antipsoriatic agent, specifically for the treatment of psoriasis. It helps in managing the symptoms and reducing the severity of the skin condition.
Used in Tape Product Formulation:
Flurandrenolide is used in the formulation of tape products, such as Cordran (Oclassen) and Cordran (Watson), which can stick to and remove damaged skin. However, caution should be exercised when using these products with vesicular or weeping dermatoses due to the potential for skin damage.

Originator

Haelan ,Lilly ,UK ,1962

Indications

Flurandrenolide (Cordran, Cordran SP) is a synthetic fluorinated corticosteroid.

Therapeutic Function

Glucocorticoid, Antiinflammatory

Biological Functions

Corticosteroids influence all tissues of the body and produce numerous and varying effects in cells. These steroids regulate carbohydrate, lipid, and protein biosynthesis and metabolism (glucocorticoid effects), and they influence water and electrolyte balance (mineralocorticoid effects). Cortisol is the most potent glucocorticoid secreted by the adrenal gland, and aldosterone is the most potent endogenous mineralocorticoid. Both naturally occurring glucocorticoids and related, semisynthetic analogues can be evaluated in terms of their ability to sustain life, to stimulate an increase in blood glucose concentrations and a deposition of liver glycogen, to decrease circulating eosinophils, and to cause thymus involution in adrenalectomized animals. In addition, corticosteroids can affect immune system functions, inflammatory responses, and cell growth. The primary physiologic function of glucocorticoids is to maintain blood glucose levels and, thus, ensure glucose-dependent processes critical to life, particularly brain functions. Cortisol and related steroids accomplish this by stimulating the formation of glucose, by diminishing glucose use by peripheral tissues, and by promoting glycogen synthesis in the liver to increase carbohydrate stores for later release of glucose.

Mechanism of action

Glucocorticoid action is mediated through the glucocorticoid receptor, which is found primarily in the cytosol of the cell when not bound to glucocorticoids. The GR is stabilized in the cytosol by complexation with phosphorylated proteins, including a 90-kDa protein referred to as a heat shock protein 90. The steroid molecule binds to the GR, resulting in a conformational change of the receptor to dissociate the other proteins and initiate translocation of the steroid–receptor complex into the nucleus. The steroid–nuclear GR complex interacts with particular HRE regions of the cellular DNA, referred to as glucocorticoid-responsive elements and initiates transcription of the DNA sequence to produce mRNA. Finally, the elevated levels of mRNA lead to increased protein synthesis in the endoplasmic reticulum. These proteins then mediate glucocorticoid effects on carbohydrate, lipid, and protein metabolism. An alternative isoform of the GR has been identified. This isoform of the receptor does not bind known glucocorticoids, and its function remains to be determined.

Clinical Use

Two major uses of glucocorticoids are in the treatment of rheumatoid diseases and allergic manifestations. Their use in the treatment of severe asthma is well documented, as is the utility of glucocorticoids in sepsis and acute respiratory distress syndrome. They are effective in the treatment of rheumatoid arthritis, acute rheumatic fever, bursitis, spontaneous hypoglycemia in children, gout, rheumatoid carditis, sprue, allergy (including contact dermatitis), and other conditions. The treatment of chronic rheumatic diseases and allergic conditions with glucocorticoids is symptomatic and continuous. Symptoms return after withdrawal of the drug.

Side effects

Although side effects and toxicities vary with the drug and, sometimes, with the patient, facial mooning, flushing, sweating, acne, thinning of the scalp hair, abdominal distention, and weight gain are observed with most glucocorticoids. Protein depletion (with osteoporosis and spontaneous fractures), myopathy (with weakness of muscles of the thighs, pelvis, and lower back), and aseptic necrosis of the hip and humerus are other side effects.

InChI:InChI=1/C24H33FO6/c1-21(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/h7,13-14,16-17,19-20,26,28H,5-6,8-11H2,1-4H3/t13?,14?,16-,17-,19+,20?,22-,23-,24+/m0/s1

Synthetic route

flunisolide (3385-03-3, 3870-63-1, 79284-83-6) → flurandrenolide (1524-88-5)

Conditions	Yield
With Wilkinson's catalyst; hydrogen In ethanol; toluene for 65h; Ambient temperature;	76%
(tris(triphenylphosphine)rhodium) chloride In ethanol; chloroform; toluene
(tris(triphenylphosphine)rhodium) chloride In ethanol; chloroform; toluene

flurandrenolide (1524-88-5) + butyraldehyde (123-72-8) → (4aR,4bS,5S,6aS,6bS,8R,9aR,10aS,10bS,12S)-12-Fluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4a,6a-dimethyl-8-propyl-3,4,4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-tetradecahydro-7,9-dioxa-pentaleno[2,1-a]phenanthren-2-one + (4aR,4bS,5S,6aS,6bS,8S,9aR,10aS,10bS,12S)-12-Fluoro-5-hydroxy-6b-(2-hydroxy-acetyl)-4a,6a-dimethyl-8-propyl-3,4,4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-tetradecahydro-7,9-dioxa-pentaleno[2,1-a]phenanthren-2-one

Conditions	Yield
With hydrogenchloride at -15 - -10℃; for 2h;	A 39% B 27%

flurandrenolide (1524-88-5) + barium(II) acetate (543-80-6) → 21-(acetyloxy)-6α-fluoro-11β-hydroxy-16α,17-<(1-methylethylidene)bis(oxy)>pregna-1,4-diene-3,20-dione (4533-89-5)

Conditions	Yield
1.) Corynebacterium simplex, DMF, 20 h, 2.) glacial acetic acid, acetic anhydride, room temp., 24 h; Yield given. Multistep reaction;

flurandrenolide (1524-88-5) → 6α-Fluoro-16α,17α-isopropylidenedioxandrost-4-en-11β-ol-3-one-17β-carboxylic acid (75578-60-8)

Conditions	Yield
With potassium hydroxide; oxygen In methanol; dichloromethane for 6h; Ambient temperature; Yield given;

flurandrenolide (1524-88-5) + n-hexadecanoyl chloride (112-67-4) → 6α-Fluoro-11β-hydroxy-16α,17α-[(1-methylethylidene)bis(oxy)]-21-palmitoyloxypregn-4-ene-3 20-dione (144653-70-3)

Conditions	Yield
In 1,4-dioxane; pyridine; ethanol; n-heptane; chloroform

Upstream product

• 1526-01-8 (4aR,6aS,6bS,9aR,12S)-12-Fluoro-6b-(2-hydroxy-acetyl)-4a,6a,8,8-tetramethyl-3,4,4a,4b,5,6,6a,6b,9a,10,10a,10b,11,12-tetradecahydro-7,9-dioxa-pentaleno[2,1-a]phenanthren-2-one 
• 3385-03-3 flunisolide 

Downstream Products

• 4533-89-5 21-(acetyloxy)-6α-fluoro-11β-hydroxy-16α,17-<(1-methylethylidene)bis(oxy)>pregna-1,4-diene-3,20-dione 

Relevant academic research and scientific papers

6α-fluoro- and 6α,9α-difluoro-11β,21-dihydroxy- 16α,17α- propylmethylene-dioxypregn-4-ene-3,20-dione: Synthesis and evaluation of activity and kinetics of their C-22 epimers

It is generally accepted that the anti-inflammatory, effect of glucocorticosteroids cannot be separated from their adverse effects at the receptor level. However, modification of the pharmacokinetics through structural alterations could provide steroids with a better therapeutic index than those currently used. Thus, new 16α, 17α-acetals between butyraldehyde and 6α-fluoro- or 6α, 9α-difluoro-16α-hydroxycortisol were synthesized and studied. Acetalization of the corresponding 16α, 17α-diols or transacetalization of their 16α, 17α-acetonides in dioxane produced mixtures of C-22 epimers, which were resolved by preparative chromatography. Alternatively, an efficient method was used to produce the 22R-epimer stereoselectively through performing the acetalization and transacetalization in a hydrocarbon with an inert material present. The C-22 configuration of (22R)-6α, 9α-difluoro-11β,21-dihydroxy-16α,17α- propylmethylenedioxypregn-4-ene-3,20-dione was unambiguously established by single crystal X-ray diffraction. The present compounds, especially the 22R- epimer just mentioned, bind to the rat thymus glucocorticoid receptor with high potency. The C-22 epimers of the 6α, 9α-difluoro derivatives showed a 10-fold higher biotransformation rate than the budesonide 22R-epimer when incubated with human liver S9 subcellular fraction. The high receptor affinity, in combination with the high biotransformation rate indicates that (22R)-6α,9α-difluoro-11β,21-dihydroxy-16α,17α-propylmethylenedioxypregn- 4-ene-3,20-dione may be an improved 16α, 17α-acetal glucocorticosteroid for therapy of inflammatory diseases, in which the mucous membranes are involved, such as those in the intestinal tract as well in the respiratory tract.

STEROID DERIVATIVES ACTING AS GLUCOCORTICOSTEROID RECEPTOR AGONISTS

The present invention provides compounds of formula (I) wherein n, p, R1, R2, X1, X2 , X3, R3a, R3b, R4, R5 and R6 are as defined in the specification, a process for their preparation, pharmaceutical compositions containing them and their use in therapy.

Method for reducing or preventing transplant rejection in the eye and intraocular implants for use therefor

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.

Composition for the topical treatment of poison ivy and other forms of contact dermatitis

Composition for topical administration comprising (a) a corticosteroid, and (b) a drying agent.

Smilagenin and its use

The invention discloses the use of a smilagenin in the treatment of cognitive disfunction and similar conditions. Methods of treatment, and pharmaceutical compositions are also disclosed.

Steroid esters

The invention concerns compounds of formula I STR1 in which R1 is hydrogen or a straight or branched hydrocarbon chain; R2 is hydrogen or a straight or branched hydrocarbon chain; R3 is acyl; X1 is hydrogen, fluorine or chlorine; and X2 is hydrogen, fluorine or chlorine. Also disclosed are processes for preparation of the compounds, pharmaceutical compositions containing them and methods employing the compounds in the treatment of inflammatory and allergic conditions.

STEROID ESTERS

Compounds of the general formula (I), in which formula the 1,2-position is saturated or is a double bond, R1 is hydrogen or a straight or branched hydrocarbon chain, R2 is hydrogen or a straight or branched hydrocarbon chain, R3 is acyl, X1 is hydrogen or halogen, X2 is hydrogen or halogen and provided that 1) R1 and R2 are not simultaneously hydrogen, 2) X1 and X2 are not simultaneously hydrogen, 3) when the 1,2-position is a double bond, R1 and R2 are not simultaneously methyl groups, 4) when the 1,2-position is a double, R1 is a hydrogen atom and R2 is a straight or branched hydrocarbon chain having 1-10 carbon atoms R3 is acyl having 11-20 carbon atoms, processes for their preparation, pharmaceutical preparations containing them and the use of the compounds in the treatment of inflammatory and allergic conditions

Sulfonate containing ester prodrugs of corticosteroids

Novel solution stable ester prodrugs of corticosteroids of the formula STR1 and their salts.

Water-soluble steroid compounds

Beta-cyclodextrin forms a water-soluble complex or inclusion compound with steroid compounds having a molecular structure smaller than the interior cavity in the doughnut-shaped molecular structure of beta-cyclodextrin. The resulting inclusion compounds can be used for a variety of applications including aqueous topical ophthalmic preparations and topical dermatological ointments.