66734-13-2 Usage
Uses
Used in Dermatology:
Alclometasone-17,21-dipropionate is used as a topical treatment for various skin disorders due to its glucocorticoid activity. It is particularly effective as an anti-inflammatory, antipruritic, antiallergic, antiproliferative, and vasoconstrictive agent. It is usually administered as a cream or ointment containing 0.05% and has been used since 1986 for the treatment of corticosteroid-responsive dermatoses.
Used in the Treatment of Corticosteroid-Responsive Dermatoses:
Alclometasone-17,21-dipropionate is used as a potent corticosteroid for the treatment of corticosteroid-responsive dermatoses, such as radiation, allergic contact dermatitis, and psoriasis. Its anti-inflammatory and immunosuppressive properties make it an effective treatment option for these conditions.
Used in Pharmaceutical Formulations:
Alclometasone-17,21-dipropionate is used as an active ingredient in various pharmaceutical formulations, such as creams, ointments, and lotions, for the treatment of skin disorders. Some of the brand names include Aclovate (GlaxoSmithKline), Aclosone, Legederm, Almeta, Vaderm, Modrasone, and Delonal.
Used in Research and Development:
Alclometasone-17,21-dipropionate is also used in research and development for the study of its anti-inflammatory, immunosuppressive, and other pharmacological properties. This helps in the development of new drugs and therapies for various skin disorders and other related conditions.
Characteristics
The alclometasone dipropionate [7α-chloro-11β,17,21- trihydroxy-16α-methylpregna-1,4-dien-3,20-dione 17,21- dipropionate) molecule is obtained by insertion of a chlorine atom in position 7α of 16α-me thylprensoline 17,21-dipropionate. The unique properties of the compound result from the presence of a chlorine atom in position 7α instead of positions C6 or C9, which increases the potency of its effect without increasing the incidence of local and systemic adverse effects. Additionally, as a highly lipophilic compound, alclometasone dipropionate rapidly penetrates into the skin where its active metabolites bind to specific receptors.
Preparation
Alclometasone dipropionate synthesis: The dehydrogenation of 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4-diene-3,20-dione-21-acetate (I) with dichlorodicyanobenzoquinone (II) in dioxane HCl gives 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-21-acetate (III), which is hydrolyzed with aqueous NaHCO3 to the corresponding free triol (IV). The reaction of (IV) with triethyl orthopropionate (A) by means of p-toluenesulfonic acid in DMSO yields 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-17,21-ethylorthopropionate (V), which is hydrolyzed partially with acetic acid to 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-17-propionate (VI). The acylation of (VI) with propionic anhydride affords 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-17,21-dipropionate (VII), which is finally treated with dry HCl in dioxane.
Therapeutic Function
Antiinflammatory, Antiallergic
Side effects
The following local adverse reactions have been reported with alclometasone dipropionate cream in approximately 2% of patients: itching and burning, erythema, dryness, irritation, and papular rashes.The following local adverse reactions have been reported with alclometasone dipropionate ointment in approximately 1% of patients: itching, burning, and erythema. The following additional local adverse reactions have been reported infrequently with topical corticosteroids, but may occur more frequently with the use of occlusive dressings. These reactions are listed in approximate decreasing order of occurrence: folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, skin atrophy, striae, and miliaria.
Safety Profile
Alclometasone dipropionate has been classified as the FDA category C of drug safety during pregnancy (irrespective of the trimester of pregnancy), which means that it should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the foetus. The safety of alclometasone use in paediatric patients below 1 year of age has not been established and there are no adequate, randomised studies in large patient groups.
Mode of action
At the cellular level, alclometasone dipropionate, like other glucocorticoids, after crossing the cell membrane binds to specific glucocorticoid receptors (GCR) in the cytoplasm. Subsequently, the glucocorticoid-GCR complex moves into the nucleus, where its binds to DNA at specific regions, known as the glucocorticoid response elements (GRE). At further stages, the expression of certain genes is either stimulated (transactivation) or inhibited (transuppression). In clinical practice, glucocorticoids are used for their anti-inflammatory, immunosuppressant and antiproliferative effects.
Check Digit Verification of cas no
The CAS Registry Mumber 66734-13-2 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 6,6,7,3 and 4 respectively; the second part has 2 digits, 1 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 66734-13:
(7*6)+(6*6)+(5*7)+(4*3)+(3*4)+(2*1)+(1*3)=142
142 % 10 = 2
So 66734-13-2 is a valid CAS Registry Number.
InChI:InChI=1/C28H37ClO7/c1-6-22(33)35-14-21(32)28(36-23(34)7-2)15(3)10-18-24-19(29)12-16-11-17(30)8-9-26(16,4)25(24)20(31)13-27(18,28)5/h8-9,11,15,18-20,24-25,31H,6-7,10,12-14H2,1-5H3/t15-,18+,19-,20+,24-,25+,26+,27+,28+/m1/s1
66734-13-2Relevant articles and documents
Method for preparing etherified intermediate for alclometasone dipropionate
-
Paragraph 0032; 0034; 0041; 0042; 0049; 0050; 0057, (2019/06/07)
The invention provides a method for preparing an etherified intermediate for alclometasone dipropionate. 16a-methylhydrocortisone used as a raw material undergoes a four-step reaction comprising propionation at the 21-position, double oxidation at 7- and 11-positions into double ketones, propionation at the 17-position and enolification and etherification protection at the 3-position to synthesizethe etherified intermediate for alclometasone dipropionate. The method for preparing the etherified intermediate for alclometasone dipropionate from the 16a-methylhydrocortisone through the four-stepreaction has the advantages of short synthesis route, economical and environmentally-friendly process, simplicity in production operation, and high product yield; and the solvent used in production can be recovered and recycled, and so the method achieves easy industrial production.
Method for preparing reduced intermediate product for aclomethasone dipropionate
-
, (2019/04/30)
The invention provides a method for preparing a reduced intermediate product for aclomethasone dipropionate. The method comprises the steps that with 16a-methyl pihydrocortisone as a raw material, a crude reduced intermediate product for aclomethasone dipropionate is synthesized through a five-step reaction of 21-site propionic acid esterification, 7,11-site double-oxidation into diketone, 17-sitepropionic acid esterification, 3-site enolization etherification protection and 7,11-site diketone reduction and acid hydrolysis deprotection, then the reduced intermediate product for aclomethasonedipropionate is obtained through refining. By means of the method, with 16a-methyl pihydrocortisone as the raw material, the reduced intermediate product for aclomethasone dipropionate is synthesizedthrough the five-step reaction; the process has the advantages of being short in synthesis route, economical, environmentally friendly, simple in production operation, high in product yield and the like; a solvent used in production can be recycled and applied, and industrial production is easy to implement.
Method of reduced intermediate used for alclometasone-17,21-dipropionate
-
, (2019/06/27)
The invention provides a method of a reduced intermediate used for alclometasone-17,21-dipropionate. The method comprises the steps that 16alpha-methlhydrocortisone as a raw material is subjected to 21-position propionic esterification, 7- and 11-position double oxidation to form diketone, 17-position propionic esterification, 3-position enolization etherification protection and 7- and 11-positiondiketone reduction and acid hydrolysis deprotection, and then the reduced intermediate used for the alclometasone-17,21-dipropionate is synthesized. In the method, the 16alpha-methlhydrocortisone serves as the raw material and is subjected to reactions in five steps to form the reduced intermediate used for the alclometasone-17,21-dipropionate, the technology has the advantages of being short insynthesis route, economical, environmentally friendly, simple in production operation and high in product yield; the solvent used in the production process can be recycled, and industrial production is easily implemented.
Synthesis and structure-activity studies of a series of 7α-halogeno corticosteroids
Shue,Green,Berkenkoph,Monahan,Fernandez,Lutsky
, p. 430 - 437 (2007/10/02)
The preparation and topical antiinflammatory potencies of a series of 7α-halogeno-16-substituted-prednisolone derivatives are described. The 7α-chloro, 7bromo, and 7α-iodo corticosteroids were obtained by addition of hydrogen halide to the 6,7-dehydro compounds. The extent of addition of HCl varied with substitution at C-11, while no addition of HF was observed at all. The 7α-fluoro corticosteroids were prepared by reaction of the appropriate 7β-hydroxy compounds with N,N-diethyl(2-chloro-1,1,2-trifluoroethyl)amine. The 7β-hydroxy steroids were obtained, in turn, from the 6,7-dehydro compounds via the 6β,7β-dihydroxy derivatives. Antiinflammatory potencies were measured in mice by the Tonelli croton oil ear assay. The greatest effect of 7α-halogen was observed in the 16α-methylprednisolone series, where 7α-chloro and 7α-bromo substitution increased potency 2.5- to 3.5-fold. Compounds 4b and 5b (the 7α-chloro, respectively 7α-bromo-methyl-prednisolone 17,21-dipropionate, t.w., 7α-chloro,respectively 7α-bromo-16α-methyl-11β,17α,21-trihydroxy-1,4-pregnadiene-3,20-dione 17,21-dipropionate) were equipotent to betamethasone dipropionate. 7α-Halogen substitution in other series produced more variable effects and sometimes led to a reduction of antiinflammatory potency.
7α-Halogeno-3,20-dioxo-1,4-pregnadienes, methods for their manufacture, their use as anti-inflammatory agents, and pharmaceutical formulations useful therefor
-
, (2008/06/13)
Novel 3,20-dioxo-7α-halogeno-1,4-pregnadienes are described and their use as anti-inflammatory agents. Preferred are 7α-bromo- and 7α-chloro- derivatives, particularly 7α-bromo- and 7α-chloro-1,4-pregnadienes-11β,17α,21-triol-3,20-dione 17,21-dihydrocarboncarboxylates, the 16-methyl and 16-methylene derivatives thereof being particularly valuable as topical anti-inflammatory agents.