- Method for preparing etherified intermediate for alclometasone dipropionate
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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.
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Paragraph 0032; 0034; 0041; 0042; 0049; 0050; 0057
(2019/06/07)
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- Method for preparing reduced intermediate product for aclomethasone dipropionate
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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.
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- Method of reduced intermediate used for alclometasone-17,21-dipropionate
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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.
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- Synthesis and structure-activity studies of a series of 7α-halogeno corticosteroids
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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.
- Shue,Green,Berkenkoph,Monahan,Fernandez,Lutsky
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p. 430 - 437
(2007/10/02)
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- 7α-Halogeno-3,20-dioxo-1,4-pregnadienes, methods for their manufacture, their use as anti-inflammatory agents, and pharmaceutical formulations useful therefor
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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.
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