Betamethasone CAS 378-44-9

Introduction：Basic information about Betamethasone CAS 378-44-9, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Betamethasone Basic information

• Product Name: Betamethasone
• Synonyms: 17,21-trihydr;betamethasone standard;(8S,9R,10S,11S,13S,14S,16S,17R)-9-fluoro- 11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl- 6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one;Betamethasone Base & Salts;Betamethasone,9α-Fluoro-11β,17α,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione, 9α-Fluoro-16β-methyl-11β,17α,21-trihydroxy-1,4-pregnadiene-3,20-dione, 9α-Fluoro-16β-methylprednisolone;Betamethasone (200 mg);BetaMethasone (Celestone);BetaMethasone SolutioM
• CAS: 378-44-9
• MF: C22H29FO5
• MW: 392.47
• EINECS: 206-825-4
• Product Categories: CELESTONE;Pharmaceutical intermediate;Steroid and Hormone;Intermediates & Fine Chemicals;Pharmaceuticals;Biochemistry;Hydroxyketosteroids;Steroids;API;378-44-9
• Mol File: 378-44-9.mol

Betamethasone Chemical Properties

• Melting point: 235-237°C
• alpha: D +108° (acetone)
• Boiling point: 568.2±50.0 °C(Predicted)
• density: 1.1283 (estimate)
• refractive index: 118 ° (C=1, Dioxane)
• storage temp.: 0-6°C
• solubility: Practically insoluble in water, sparingly soluble in anhydrous ethanol, very slightly soluble in methylene chloride.
• pka: 12.13±0.70(Predicted)
• form: Solid
• color: White to Off-White
• biological source: synthetic (organic)
• Water Solubility: 58mg/L(25 ºC)
• Merck: 14,1180
• InChIKey: UREBDLICKHMUKA-DVTGEIKXSA-N
• SMILES: [H][C@@]12C[C@H](C)[C@](O)(C(=O)CO)[C@@]1(C)C[C@H](O)[C@@]3(F)[C@@]2([H])CCC4=CC(=O)C=C[C@]34C
• LogP: 2.01 at 25℃
• CAS DataBase Reference: 378-44-9(CAS DataBase Reference)
• NIST Chemistry Reference: Pregna-1,4-diene-3,20-dione, 9alpha-fluoro-11beta,17alpha,21-trihydroxy-16beta-methyl-(378-44-9)
• EPA Substance Registry System: Pregna-1,4-diene-3,20-dione, 9-fluoro-11,17,21-trihydroxy-16-methyl-, (11.beta.,16.beta.)- (378-44-9)

Safety Information

• Hazard Codes: Xi,Xn,T
• Risk Statements: 40-48/20/21-61
• Safety Statements: 22-36-45-53
• WGK Germany: 2
• RTECS: TU4000000
• HS Code: 29379000
• Storage Class: 6.1C - Combustible acute toxic Cat.3 toxic compounds or compounds which causing chronic effects
• Hazard Classifications: Repr. 1B STOT RE 2
• Hazardous Substances Data: 378-44-9(Hazardous Substances Data)
• Toxicity: LD50 oral in mouse: > 4500mg/kg

Betamethasone Usage And Synthesis

hormone drugs

Betamethasone, belongs to adrenal corticosteroids, it is a isomer of dexamethasone , and the role of betamethasone is similiar to prednisolone and dexamethasone , it has anti-inflammatory, anti-rheumatic, anti-allergic and suppression of the immune and other pharmacological effects, its anti-inflammatory effect is stronger than dexamethasone, triamcinolone, hydrocortisone etc. , it can reduce and prevent tissue response to inflammation and eliminate heat, redness and swelling caused by local non-infectious inflammation, thereby reducing the performance of inflammation, anti-inflammatory effect of this product 0.3mg is equal to dexamethasone 0.75mg, prednisone 5mg or 25mg cortisone .
Betamethasone sodium retention effect is a hundred times more than hydrocortisone, in primary adrenal hypofunction, it can be used together with glucocorticoid for replacement therapy ,and it is used for preventing or inhibiting cell-mediated immune response, delaying allergic reactions and reducing the primary immune response expansion ,it is used for low renin and low aldosterone syndrome and autonomic neuropathy induced orthostatic hypotension.
Currently betamethasone is also used for the treatment of active rheumatoid arthritis, rheumatoid arthritis, lupus, severe bronchial asthma, severe dermatitis, acute leukemia, atopic dermatitis, eczema, neurodermatitis, seborrheic dermatitis, and pruritus and comprehensive treatment of certain infections.
The product is contraindicated in severe psychiatric history, active duodenal ulcer, recent gastrointestinal anastomosis, heavier osteoporosis, overt diabetes, severe hypertension, virus , bacterial, fungal infections which are failed to control by the use of antimicrobial agents , thrombophlebitis, skin infections, such as impetigo, tinea, jock itch and so on.
The above information is edited by the chemicalbook of Tian Ye.

Chemical Properties

White crystalline powder. Mp 231-234 deg.] C (decomposition). Odorless. Acetate Betamethasone ([987-24-6]) is also white crystalline powder, melting point 205-208 ℃, slightly soluble in alcohol, ethanol, and very slightly soluble in chloroform or ether, insoluble in water, odorless.

Uses

Hormone drugs.It is mainly used for anti-inflammatory and anti-allergic. It is suitable for rheumatoid arthritis and various skin diseases. Betamethasone role is similiar to dexamethasone, its anti-inflammatory effect is stronger than dexamethasone, triamcinolone, hydrocortisone and it has few side effects.

production method

According to U.S. Patent No. 3,164,618, betamethasone acetate is dealt with hydrochloric acid in methanol-chloroform-water mixture , it can be converted to betamethasone.

Category

Toxic substances

Toxicity grading

Middle toxic

Acute toxicity

Oral-mouse LD50:> 4500 mg/kg

Flammability and hazard characteristics

Combustible;Its combustion produces toxic fumes of fluoride.

Storage Characteristics

Ventilated, low-temperature ,dry storeroom.

Extinguishing agent

Dry powder , foam, sand, carbon dioxide, water spray.

Description

Shortly after the introduction of dexamethasone, betamethasone, which differs from dexamethasone only inconfiguration of the 16-methyl group, was made available for the treatment of rheumatic diseasesand dermatologic disorders. This analogue, which contains a 16β-methyl group, has received sufficient clinicaltrial examination to indicate that it is as effective as dexamethasone or, perhaps, even slightly more active.Although this drug has been reported to be less toxic than other steroids, some clinical investigators suggestthat it is best used for short-term therapy.

Description

Betamethasone is a synthetic corticosteroid. Like other corticosteroids, betamethasone has anti-inflammatory actions. Betamethasone also accelerates fetal lung maturation and has been used to decrease neonatal mortality and morbidity in infants born before 34 weeks of gestation.

Chemical Properties

White to Off-White Solid

Originator

Celestone,Schering,US,1961

Uses

glucocorticoid, antiinflammatory

Uses

Betamethasone is a glucocorticoid used as an anti-inflammatory agent.

Uses

anti-inflammatory, immunosuppressive

Definition

ChEBI: Betamethasone is a glucocorticoid, a 20-oxo steroid, a 21-hydroxy steroid, a 17alpha-hydroxy steroid, a fluorinated steroid, an 11beta-hydroxy steroid, a 3-oxo-Delta(1),Delta(4)-steroid, a primary alpha-hydroxy ketone and a tertiary alpha-hydroxy ketone. It has a role as an anti-inflammatory drug, an anti-asthmatic agent and an immunosuppressive agent. It derives from a hydride of a pregnane.

Manufacturing Process

Betamethasone acetate is converted to betamethasone by means ofhydrochloric acid in a methanol-chloroform-water mixture as described in USPatent 3,164,618.

Brand name

Celestone Syrup and Tablets (Schering).

Therapeutic Function

Glucocorticoid

General Description

Betamethasone, 9-fluoro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dione,is available as a variety of ester derivatives.
Betamethasone valerate, USP (17-valerate)
Betamethasone acetate, USP (21-acetate)
Betamethasone sodium phosphate, USP (21-sodiumphosphate)
Betamethasone dipropionate, USP (17-propionate,21-propionate).

Flammability and Explosibility

Non flammable

Biochem/physiol Actions

Betamethasone, an?isomer?of dexamethasone is also termed as 9α-fluoro-16β-methyl-11 β,17,21-trihydroxypregna-1,4-dien-3,20-dione or 9α-fluoro-16β-methylprednisolone (27.1.52). It can be used as an anti-itch agent and treating dermatitis?and?eczema.

Clinical Use

Corticosteroid:

Suppression of inflammatory and allergic disorders

Congenital adrenal hyperplasia

Side effects

Toxic side effects, such as increased appetite, weight gain, andfacial mooning, occur with prolonged use.

Safety Profile

Low toxicity by ingestion. Anexperimental teratogen. Other experimental reproductiveeffects. When heated to decomposition it emits toxicfumes of F-.

Synthesis

Betamethasone is 9α-fluoro-16β-methyl-11 β,17,21-trihydroxypregna-1,4-dien-3,20-dione, or simply 9α-fluoro-16β-methylprednisolone (27.1.52). As seen fromthe chemical name of the drug, betamethasone only differs from dexamethasone in the orientationof the methyl group at C16. The proposed method of synthesis differs from the othermethod in a number of details and successive reactions besides the first stage, in particularconcerning the addition of the methyl group at C16 of the steroid ring. Betamethasone, likedexamethasone, is synthesized from 3α-acetoxy-16-pregnen-11,20-dione; however, themethyl group at C16 of the steroid ring is not reacted with methylbromide, but rather isreacted with diazomethane followed by hydrogenation of the double bond between carbonatoms C16–C17 of the steroid ring using a palladium on carbon catalyst, which results in thecorresponding β-orientation of the introduced methyl group.

Drug interactions

Potentially hazardous interactions with other drugs Aldesleukin: avoid concomitant use. Antibacterials: metabolism accelerated by rifampicin; 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 primidone.
Antifungals: increased risk of hypokalaemia with amphotericin - avoid; metabolism possibly inhibited by itraconazole and ketoconazole.
Antivirals: concentration possibly increased by ritonavir.
Ciclosporin: rare reports of convulsions in patients on ciclosporin and high-dose corticosteroids.
Cobicistat: concentration of betamethasone possibly increased.
Diuretics: enhanced hypokalaemic effects of acetazolamide, loop diuretics and thiazide diuretics.
Vaccines: high dose corticosteroids can impair immune response to vaccines; avoid 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.

Purification Methods

Betamethasone crystallises from ethyl acetate, and has max at 238nm (log 4.18) in MeOH. The 21-acetate [287-24-6] crystallises from Me2CO/Et2O (charcoal) m 196-201o (205-208o) and has [] D 20 +140o (CHCl3). [Taub et al. J Am Chem Soc 82 4012 1960, Olivetto et al. J Am Chem Soc 80 6688 1958, Beilstein 8 IV 3501.]

references

[1] pharmacology review(s)-fda.

Betamethasone Preparation Products And Raw materials

• Raw materials: Betamethasone 21-acetate-->Hydrochloric acid-->6 beta-hydroxybetamethasone 17-propionate-->Betamethasone 17,21-dipropionate-->6-hydroxybetamethasone-->9-fluoro-11beta,17,21-trihydroxy-16beta-methylpregna-1,4-diene-3,20-dione 17-propionate