50-02-2 Usage
Description
Dexamethasone is an anti-inflammatory glucocorticoid, chemically known as 9-fluoro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione, and is the 16-isomer of betamethasone. It is an odorless white to off-white crystalline powder with a slightly bitter taste. Dexamethasone is used to treat inflammatory and autoimmune conditions such as rheumatoid arthritis and bronchospasm. It is also useful for studying apoptosis, cell signaling pathways, and gene expression. Additionally, it is associated with marbofloxacin and clotrimazole and finds application in veterinary medicine.
Uses
Used in Medical Applications:
Dexamethasone is used as a glucocorticoid for treating various conditions, including circulatory collapse, shock during or after surgical operations, trauma, blood loss, myocardial infarction, and burns. It is also used in severe infections such as toxemia, vascular collapse in meningococcosis, septicemia, diphtheria, typhoid fever, and peritonitis.
Used in Allergic Conditions:
Dexamethasone is used as an anti-inflammatory glucocorticoid for treating severe allergic conditions, including asthmatic status, laryngeal edema, severe anaphylactic reactions to medicinal drugs, and pyrogenic reactions.
Used in Inflammatory and Autoimmune Conditions:
Dexamethasone is used as an anti-inflammatory glucocorticoid for treating inflammatory and autoimmune conditions such as rheumatoid arthritis and bronchospasm.
Used in Veterinary Medicine:
Dexamethasone is used in combination with trichlormethiazide to treat horses with swelling of distal limbs and general bruising. It is also associated with marbofloxacin and clotrimazole to treat difficult ear infections in dogs.
Used in Research:
Dexamethasone is used to study apoptosis, cell signaling pathways, and gene expression due to its various biological activities, such as inducing the production of phospholipase A2 inhibitory protein (lipocortin), inhibiting the induction of nitric oxide synthase, and regulating T cell survival, growth, and differentiation.
Chemical Properties:
Dexamethasone is a white or almost white, crystalline powder.
Brand Names:
Aeroseb-Dex (Allergan), Decadron (Merck), Dexone (Solvay Pharmaceuticals), Hexadrol (Organon), Maxidex (Alcon), Mymethasone (Morton Grove).
Anti-inflammatory effects
Dexamethasone reduces and prevents the tissue response to inflammation, thereby reducing the manifestations of inflammation. Hormones inhibit the accumulation of inflammatory cells, including macrophages and leukocytes, at sites of inflammation, and inhibit phagocytosis, the release of lysosomal enzymes, and the synthesis and release of inflammatory chemical mediators.
Side Effects
Dexamethasone is a artificially synthetic glucocorticoid, belonging to a long-term glucocorticoid drugs. Glucocorticoids can promote the metabolism of the three major nutrients while preventing protein synthesis with long-term topical being able to causing more serious consequences. However, the adverse effects should be much smaller than oral medication. Common side effects of systemic corticosteroid include:
It can cause stomach discomfort and increased sensitivity to stomach ulcers.
It can Increase the appetite and results in a significant increase in body weight.
Potential patients with diabetes: glucose intolerance in patients with aggravating existing diabetes.
It can cause mental illness including personality changes, irritability, agitation, and mania.
It can be used for the long-term treatment of osteoporosis: pathological fractures (such as hip).
It can cause elevated liver enzymes, fatty liver degeneration (usually reversible).
For patients of nephrotic syndrome, applying long-term high-dose medication is likely to cause large side effects such as gastrointestinal ulcers and avascular necrosis. For treatment of nephrotic syndrome, it is better to apply prednisone acetate tablets.
Dexamethasone can be used for the treatment of high altitude cerebral edema and pulmonary edema. Upon climbing expeditions, people can apply it to alleviate altitude sickness.
Combination with marbofloxacin and clotrimazole, etc. can be used for treating the ear infection and allergies of a dog or a bird.
The above information is edited by the lookchem of Dai Xiongfeng.
Drug Reactions
Dexamethasone is a corticosteroid known as a glucocorticoid. Corticosteroids are meant to resemble a naturally occurring hormone produced in the adrenal cortex, cortisol. Corticosteroids act on the immune system by blocking the production of substances that trigger inflammatory and immune responses.
Dexamethasone may react with these drugs:
Amphotericin
Aspirin
Cyclophosphamide
Cyclosporine
Digoxin
Daunorubicin HCl
Doxorubicin HCl
Insulin
Mitotane
Phenobarbital
Phenytoin sodium
Rifampin
Rimadyl
Indications
Cushing’s disease is defined as hypercortisolism due to
chronic overproduction of corticotrophin by a corticotroph
adenoma. Cortisol’s lack of suppressibility during
the administration of low doses of dexamethasone
but suppressibility during high-dose dexamethasone is
the key diagnostic finding in 99% of the patients with
Cushing’s disease. This contrasts with the lack of glucocorticoid
suppressibility typically found in patients with
corticotrophin-independent hypercortisolism (Cushing’s
syndrome). A judicious selection of the available tests
may be necessary to obtain an accurate diagnosis in patients
with Cushing’s syndrome.
Air & Water Reactions
Insoluble in water.
Reactivity Profile
Dexamethasone may be sensitive to prolonged exposure to light. Dexamethasone is incompatible with strong oxidizers, strong acids, acid chlorides and acid anhydrides. Oxidation may occur with bases.
Fire Hazard
Flash point data for Dexamethasone are not available; however, Dexamethasone is probably combustible.
Biological Activity
Glucocorticoid; anti-inflammatory. Reduces levels of activated NF- κ B in immature dendritic cells (DCs) and inhibits differentiation into mature DCs.
Biochem/physiol Actions
Target IC50: 5 nM Inhibiting the expression of inducible but not constitutive nitric oxide synthase in vascular endothelial cells
Pharmacology
Dexamethasone is a corticosteroid with high glucocorticoid activity and
virtually no mineralocorticoid activity. I ts mechanism of action as an
antiemetic is unknown, but it is possible that either direct genomic or
indirect non-genomic effects on 5-HT3 and GABAA receptors contribute to its
antiemetic activity. Many of the original studies were carried out using 8–
10mg of dexamethasone phosphate, but smaller doses (2.5–4mg) provide
equal antiemetic efficacy with minimal risk of adverse effects. Concerns
relating to adrenal suppression and other steroid-induced adverse effects
(including increased risk of bleeding) after a single dose of dexamethasone
remain largely unfounded. O ne of the most unpleasant adverse effects of
dexamethasone involves intense perineal stimulation after rapid i.v.
injection.
Pharmacokinetics
The activity of dexamethasone, as
measured by glycogen deposition, is 20 times greater than that of hydrocortisone. It has five times the
anti-inflammatory activity of prednisolone. Clinical data indicate that this compound has seven times the
antirheumatic potency of prednisolone. It is roughly 30 times more potent than hydrocortisone. Its
pharmacokinetics are presented in Table 33.3. Routes of metabolism for dexamethasone are similar to those for
prednisolone, with its primary 6β-hydroxy metabolite being recovered in urine. Dexamethasone sodium
phosphate is the water-soluble sodium salt of the 21-phosphate ester, with an IV half-life of less than 10
minutes because of rapid hydrolysis by plasma phosphatases. Peak plasma levels for dexamethasone
usually are attained in approximately 10 to 20 minutes following its IV administered dose. A similar reaction
occurs when the phosphate ester is applied topically or by inhalation.
Clinical Use
Corticosteroid:Cerebral oedemaBacterial meningitis (unlicensed indication)Suppression of inflammatory and allergic disordersRheumatic diseaseCongenital adrenal hyperplasiaAnti-emetic (unlicensed indication)
Safety Profile
Poison by intraperitoneal and subcutaneous routes. An experimental teratogen. Experimental reproductive effects. Mutation data reported. When heated to decomposition it emits toxic fumes of F-.
Synthesis
Dexamethasone, 9α-fluoro-16α-methyl-11β,17,21-trihydroxypregna-
1,4-dien-3,20-dione (27.1.51), or simply 9α-fluoro-16α-methylprednisolone. The distinctive
characteristic of dexamethasone is the presence of a fluorine atom at C9 of the steroid
ring.
Dexamethasone is synthesized in a multistage process from 3α-acetoxy-16-pregnen-
11,20-dione, which is reacted with methylmagnesium bromide in the presence of lithium
bromide to give 3α-hydroxy-16α-methylpregnan-11,20-dione (27.1.39), after which a 17α-
hydroxyl group is added. This is done by a reaction with acetic anhydride in the presence of
p-toluenesulfonic acid, forming the 3-acetoxy-17-enolacetate 27.1.40, which is epoxidized
by perbenzoic acid 27.1.41, and the product is hydrolyzed by an alkali to give an oxyketone
27.1.42. Addition of another hydroxyl group at C21 is accomplished by subsequent bromination
of a methyl group with molecular bromine, replacing the bromine atom with iodine, and
reacting iodide with potassium acetate, which forms the corresponding acetoxyketone
27.1.43. The hydroxyl group at C3 is oxidized to a carbonyl by chromium(VI) oxide in pyridine,
giving the 3,11,20-triketone 27.1.44, which again undergoes bromination by molecular
bromine, but at position C4. Dehydrogenation of this compound is accomplished using semicarbazide,
which results in the formation of an unsaturated triketone 27.1.45. In order to
avoid formation of semicarbazones at the keto-groups at C3 and C20, the final product is
treated with pyruvic acid. Semicarbazones are then specially formed at the keto-groups of C3
and C20, and the keto-group at C11 that does not take part in semicarbazone formation is
reduced to hydroxyl group using sodium borohydride. After removing the protective semicarbzone
groups, 21-O-acetoxy-16β-methylhydrocortisone (27.1.46) is formed. This is
reacted with potassium acetate and transformed to the epoxide 27.1.49. Reacting this with
hydrofluoric acid results in an opening of the epoxide ring, during which the fluorohydrin
27.1.50 is formed. Finally, microbiological dehydrogenation of this compound at C1–C2 and
simultaneous deacetylation gives dexamethasone (27.1.51).
Veterinary Drugs and Treatments
Glucocorticoids have been used in an attempt to treat practically
every malady that afflicts man or animal, but there are three broad
uses and dosage ranges for use of these agents. 1) Replacement of
glucocorticoid activity in patients with adrenal insufficiency, 2) as an
antiinflammatory agent, and 3) as an immunosuppressive. Among
some of the uses for glucocorticoids include treatment of: endocrine
conditions (e.g., adrenal insufficiency), rheumatic diseases (e.g.,
rheumatoid arthritis), collagen diseases (e.g., systemic lupus), allergic
states, respiratory diseases (e.g., asthma), dermatologic diseases
(e.g., pemphigus, allergic dermatoses), hematologic disorders (e.g.,
thrombocytopenias, autoimmune hemolytic anemias), neoplasias,
nervous system disorders (increased CSF pressure), GI diseases (e.g.,
ulcerative colitis exacerbations), and renal diseases (e.g., nephrotic
syndrome). Some glucocorticoids are used topically in the eye and
skin for various conditions or are injected intra-articularly or intralesionally.
The above listing is certainly not complete. For specific
dosages and indications refer to the Doses section.
High dose dexamethasone use for shock or CNS trauma is controversial;
recent studies have not demonstrated significant benefit
and it actually may cause increased deleterious effects.
Drug interactions
Potentially hazardous interactions with other drugsAldesleukin: avoid concomitant use.Antibacterials: metabolism accelerated by rifamycins;
metabolism possibly inhibited by erythromycin;
concentration of isoniazid possibly reduced.Anticoagulants: efficacy of coumarins and
phenindione may be altered.Antiepileptics: metabolism accelerated by
carbamazepine, fosphenytoin, phenobarbital,
phenytoin and primidoneAntifungals: increased risk of hypokalaemia with
amphotericin - avoid; metabolism possibly inhibited
by itraconazole and ketoconazole; caspofungin
concentration possibly reduced (may need to increase
dose).Antivirals: concentration of indinavir, lopinavir,
saquinavir and telaprevir possibly reduced; avoid
with rilpivirine; concentration possibly increased by
ritonavir.Ciclosporin: rare reports of convulsions in patients
on ciclosporin and high-dose corticosteroids.Cobicistat: concentration possibly increased by
cobicistat.Cytotoxics: possibly decreases axitinib concentration,
increase dose of axitinib.Diuretics: enhanced hypokalaemic effects of
acetazolamide, loop diuretics and thiazide diuretics.Netupitant: concentration of dexamethasone
increased - halve dexamethasone dose.Vaccines: high dose corticosteroids can impair
immune response to vaccines; avoid concomitant use
with live vaccines.
Metabolism
Corticosteroids are metabolised mainly in the liver
but also in other tissues, and are excreted in the urine.
The slower metabolism of the synthetic corticosteroids
with their lower protein-binding affinity may account
for their increased potency compared with the natural
corticosteroids. Up to 65% of a dose of dexamethasone is
excreted in urine within 24 hours.
Purification Methods
Dexamethasone has been recrystallised from Et2O or small volumes of EtOAc. Its solubility in H2O is 10 mg/100mL at 25o; and is freely soluble in Me2CO, EtOH and CHCl3. [Arth et al. J Am Chem Soc 80 3161 1958; for the -methyl isomer see Taub et al. J Am Chem Soc 82 4025 1960, see Beilstein 8 IV 3501.]
References
1) Merck Index 14 2943
Check Digit Verification of cas no
The CAS Registry Mumber 50-02-2 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 0 respectively; the second part has 2 digits, 0 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 50-02:
(4*5)+(3*0)+(2*0)+(1*2)=22
22 % 10 = 2
So 50-02-2 is a valid CAS Registry Number.
InChI:InChI=1/C22H29FO5/c1-12-8-16-15-5-4-13-9-14(25)6-7-19(13,2)21(15,23)17(26)10-20(16,3)22(12,28)18(27)11-24/h6-7,9,12,15-17,24,26,28H,4-5,8,10-11H2,1-3H3/t12-,15?,16+,17+,19+,20+,21+,22+/m1/s1
50-02-2Relevant articles and documents
Antigen-Drug Conjugates as a Novel Therapeutic Class for the Treatment of Antigen-Specific Autoimmune Disorders
Pickens, Chad J.,Christopher, Matthew A.,Leon, Martin A.,Pressnall, Melissa M.,Johnson, Stephanie N.,Thati, Sharadvi,Sullivan, Bradley P.,Berkland, Cory
, p. 2452 - 2461 (2019)
Multiple sclerosis represents the world's most common cause of neurological disability in young people and is attributed to a loss of immune tolerance toward proteins of the myelin sheath. Typical treatment options for MS patients involve immunomodulatory drugs, which act nonspecifically, resulting in global immunosuppression. The study discussed herein aims to demonstrate the efficacy of antigen-specific immunotherapies involving the conjugation of disease causing autoantigen, PLP139-151, and a potent immunosuppressant, dexamethasone. Antigen-drug conjugates (AgDCs) were formed using copper-catalyzed azide-alkyne cycloaddition chemistry with the inclusion of a hydrolyzable linker to maintain the activity of released dexamethasone. Subcutaneous administration of this antigen-drug conjugates to SJL mice induced with experimental autoimmune encephalomyelitis, protected the mice from a symptom onset throughout the 25 day study, demonstrating enhanced efficacy in comparison to dexamethasone treatment. These results highlight the benefits of co-delivery of autoantigens with immunosuppressant drugs as AgDCs for the treatment of autoimmune diseases.
Synthesis method and application of 9-fluorosteroid compound
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Paragraph 0089-0096; 0134-0136, (2021/01/15)
The invention provides a synthesis method and application of a 9-fluorosteroid compound, and relates to the technical field of chemical synthesis. The synthesis method of the 9-fluorosteroid compoundcomprises the following step: reacting a compound II in an ionic liquid containing hydrogen fluoride salt to obtain a 9-fluorosteroid compound III. According to the synthesis method of the 9-fluorosteroid compound, the ionic liquid containing the hydrogen fluoride salt is used as a fluorinating agent to replace a traditional hydrogen fluoride aqueous solution, volatilization of hydrogen fluoride gas is avoided, corrosivity is small, toxicity is greatly reduced, reaction conditions are mild, reaction can be completed at the room temperature, operability is high, the safety coefficient is high,and production applicability is improved. The synthesis method of the 9-fluorosteroid compound is used for preparing corticosteroid drugs, highly toxic chemical reagents are not used in the synthesisroute, the operability is high, the safety coefficient is high, and the production applicability is improved.
Ring opening and fluoridation method and device of steroidal epoxy compound
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Paragraph 0038; 0039; 0041, (2017/07/22)
The invention discloses a method of preparing a compound II, which is as shown as the following reaction formula as shown in the specification. A 9 alpha-fluorine-11 beta -hydroxyl steroidal compound II is prepared via epoxy compound ring opening and fluoridation of a steroidal epoxy compound I by taking hydrogen fluoride as a fluorination reagent in a solvent consisting of arene and water. In the formula, R is CH3, CH2OH or CH2OAc; R1 is OH; R2 is alpha-CH3 or beta-CH3; and R3 is F or H. A continuous reaction device as shown in Figure 1 can be used in the method.