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GB1009912A - Steroid compounds - Google Patents

Steroid compounds

Info

Publication number
GB1009912A
GB1009912A GB4154661A GB4154661A GB1009912A GB 1009912 A GB1009912 A GB 1009912A GB 4154661 A GB4154661 A GB 4154661A GB 4154661 A GB4154661 A GB 4154661A GB 1009912 A GB1009912 A GB 1009912A
Authority
GB
United Kingdom
Prior art keywords
compounds
general formula
acyl
hydrogen
steroids
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
GB4154661A
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck and Co Inc
Original Assignee
Merck and Co Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck and Co Inc filed Critical Merck and Co Inc
Publication of GB1009912A publication Critical patent/GB1009912A/en
Expired legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J71/00Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J41/00Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J5/00Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J75/00Processes for the preparation of steroids in general

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Steroid Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention comprises steroids of the general formula <FORM:1009912/C2/1> wherein R1 represents a b -halogen atom or a b -hydroxy or keto group but b -halogen is present at R1 only when X represents halogen, R11 represents a hydrogen or fluorine atom or a methyl group, R* represents a hydrogen atom or an a -methyl, b -methyl or methylene group, R represents a hydrogen atom or a substituted or unsubstituted alkyl, aralkyl, aryl or acyl group, R0 represents a hydrogen, iodine or fluorine atom or a hydroxy or acyloxy methylsulphonyloxy or dihydrogen phosphate group or an alkali metal salt of a dihydrogen phosphate group and X represents a hydrogen or halogen atom but hydrogen is present at not more than three, and where R represents acyl, not more than two of the four positions R11, R*, R and X, and the pyrazole ring structure has the structure shown above or the following isomeric structure <FORM:1009912/C2/2> and a process for the preparation thereof by a process commencing at any stage of the following synthesis: steroids of the general formula <FORM:1009912/C2/3> wherein R*, R1, R11 and X have the above significance but hydrogen is present at not more than two of the three positions R11, R* and X, are reacted with an aqueous formaldehyde solution in the presence of a strong acid to form steroids of the general formula <FORM:1009912/C2/4> wherein R1, R11, R* and X have the above significance but hydrogen is present at not more than two of the three positions R11, R* and X (the 11-keto compound of the last general formula may also be prepared by oxidizing the corresponding 11b -hydroxy compound with chromium trioxide in a nonaqueous base such as pyridine); the steroids of the last general formula are reacted with an alkyl formate and sodium hydride in an inert atmosphere to form the corresponding 17a ,20; 20,21 - bis - (methylenedioxy) - 2 - hydroxymethylene - 4 - pregnene - 3 - ones of the general formula <FORM:1009912/C2/5> (in the case of a reactant containing an 11b -hydroxy group, a product containing an 11b -formyloxy group is obtained); the steroids of the last general formula and the corresponding 11b -formyloxy compounds are reacted with hydrazine hydrate to form steroids of the general formula <FORM:1009912/C2/6> (which may then be reacted with an acylating agent to form products in which R represents an acyl radical), or the said steroids may be reacted with the required substituted hydrazine to form steroids of the first general formula above wherein R is other than hydrogen or acyl which steroids can also be obtained by the reaction of the corresponding steroids, wherein R is hydrogen with the required alkyl or aralkyl halide (a 17a ,20; 20,21-bis-(methylenedioxy)-9a - halogen - [3,2-c] pyrazolo - 4 - pregnene-11-one or a corresponding 11-substituted compound may be reduced to the corresponding 11b -hydroxy compound, for example by reaction with sodium borohydride); and the 17a ,20; 20,21 - bis - (methylenedioxy) - [3,2-c]-pyrazolo - 4 - pregnene compounds prepared by any of the previous processes are then treated with a dilute carboxylic acid to form steroids of the general formula <FORM:1009912/C2/7> wherein R1, R11, R* and X have the above significance, R111 represents an acyl, alkyl, aryl or aralkyl radical and R1111 represents hydrogen, an acyl group corresponding to the acid used or a mixture of the two which may be separated by chromatography. Any acyl groups present at R111 and/or R1111 may be removed by treatment with methanolic sodium methoxide. Compounds in which the 11-acyl-21-acylate grouping are derived from the same carboxylic acid are prepared by reacting a 17a ,21 - dihydroxy - [3,2-c] pyrazolo - 4 - pregnene-20-one with an acylating agent or by treating a 11-acyl-21-hydroxy compound with the same acylating agent (the use of a different acylating agent provides compounds in which the 11-acyl and 21-acyloxy groups are derived from different carboxylic acids). The 11-unsubstituted 21-acyloxy compounds are prepared by heating 11-acyl-21-acyloxy compounds with acetic acid. A 17a ,21-dihydroxy-[3,2-c] pyrazolo - 4 - pregnene - 20 - ones of the first general formula above may be reacted with methane sulphonyl chloride in a non-aqueous base to the 21-methane sulphonates (it is preferable to convert a compound in which R is hydrogen to acyl before carrying out this reaction). The 21-methanesulphonates may be converted to the 21-iodo compounds by reaction with an alkali metal iodide, and the 21-iodo compounds may be reacted with an alkali metal bisulphite to form the 21-desoxy compounds. The 21-dihydrogen phosphate esters are prepared by reacting the above 21-iodo compounds or the corresponding 21-chloro or 21-bromo compounds with a mixture of silver phosphate and phosphoric acid from which the mono- and dialkali metal salts may be obtained by neutralization with an alkali metal hydroxide (the 21-bromo compounds may be obtained by treating the 21-desoxy compounds with bromine in chloroform as described in Specification 877,085, the 21-chloro compounds may be obtained by treating the above 21 -methanesulphonates with lithium chloride in acetic acid, and the 21-bromo and the 21-chloro compounds may be obtained by treating the 21-hydroxy compounds with an excess of benzene sulphonyl bromide and chloride respectively). The 21-fluoro compounds of the first general formula above are prepared by treating the above 21-methanesulphonates with an alkali metal fluoride and are formed in a mixture with the 17a ,21-epoxy compounds of the third general formula above (the two products may be separated by chromatography. The [3,2-c] pyrazolo compounds of the invention form acid addition salts such as the hydrochloride, sulphate, chlorate, perchlorate, picrate and trichloroacetate salts. Pharmaceutical compositions having anti-inflammatory activity and are particularly useful in the treatment of arthritis contain as the active ingredients the [3,2-c] pyrazolo steroid compounds of the first two general formulae above.
GB4154661A 1960-11-23 1961-11-21 Steroid compounds Expired GB1009912A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US7117860A 1960-11-23 1960-11-23
US9470761A 1961-03-10 1961-03-10
US12996961A 1961-08-08 1961-08-08

Publications (1)

Publication Number Publication Date
GB1009912A true GB1009912A (en) 1965-11-17

Family

ID=27371831

Family Applications (1)

Application Number Title Priority Date Filing Date
GB4154661A Expired GB1009912A (en) 1960-11-23 1961-11-21 Steroid compounds

Country Status (6)

Country Link
CH (1) CH437275A (en)
DK (1) DK115769B (en)
ES (1) ES272856A1 (en)
GB (1) GB1009912A (en)
NO (1) NO122525B (en)
SE (1) SE307353B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2148899A (en) * 1983-10-29 1985-06-05 Sterwin Ag Preparing steroids in microparticulate form

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2148899A (en) * 1983-10-29 1985-06-05 Sterwin Ag Preparing steroids in microparticulate form

Also Published As

Publication number Publication date
SE307353B (en) 1969-01-07
NO122525B (en) 1971-07-12
ES272856A1 (en) 1962-04-01
CH437275A (en) 1967-06-15
DK115769B (en) 1969-11-10

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