CH531494A - Antiinflammatory pregnene-diones - Google Patents

Antiinflammatory pregnene-diones

Info

Publication number
CH531494A
CH531494A CH860472A CH860472A CH531494A CH 531494 A CH531494 A CH 531494A CH 860472 A CH860472 A CH 860472A CH 860472 A CH860472 A CH 860472A CH 531494 A CH531494 A CH 531494A
Authority
CH
Switzerland
Prior art keywords
beta
sep
pregnene
acid
methylene
Prior art date
Application number
CH860472A
Other languages
German (de)
Inventor
Andor Fuerst
Marcel Mueller
Peter Mueller
Arno Johannes Schocher
Elisabeth Becher
Original Assignee
Hoffmann La Roche
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 Hoffmann La Roche filed Critical Hoffmann La Roche
Priority to CH860472A priority Critical patent/CH531494A/en
Publication of CH531494A publication Critical patent/CH531494A/en

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01D—MEASURING NOT SPECIALLY ADAPTED FOR A SPECIFIC VARIABLE; ARRANGEMENTS FOR MEASURING TWO OR MORE VARIABLES NOT COVERED IN A SINGLE OTHER SUBCLASS; TARIFF METERING APPARATUS; MEASURING OR TESTING NOT OTHERWISE PROVIDED FOR
    • G01D9/00—Recording measured values
    • G01D9/28—Producing one or more recordings, each recording being of the values of two or more different variables
    • G01D9/30—Producing one or more recordings, each recording being of the values of two or more different variables there being a separate recording element for each variable, e.g. multiple-pen recorder
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J53/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by condensation with a carbocyclic rings or by formation of an additional ring by means of a direct link between two ring carbon atoms, including carboxyclic rings fused to the cyclopenta(a)hydrophenanthrene skeleton are included in this class
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J75/00—Processes for the preparation of steroids in general
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01D—MEASURING NOT SPECIALLY ADAPTED FOR A SPECIFIC VARIABLE; ARRANGEMENTS FOR MEASURING TWO OR MORE VARIABLES NOT COVERED IN A SINGLE OTHER SUBCLASS; TARIFF METERING APPARATUS; MEASURING OR TESTING NOT OTHERWISE PROVIDED FOR
    • G01D18/00—Testing or calibrating apparatus or arrangements provided for in groups G01D1/00 - G01D15/00
    • G—PHYSICS
    • G07—CHECKING-DEVICES
    • G07C—TIME OR ATTENDANCE REGISTERS; REGISTERING OR INDICATING THE WORKING OF MACHINES; GENERATING RANDOM NUMBERS; VOTING OR LOTTERY APPARATUS; ARRANGEMENTS, SYSTEMS OR APPARATUS FOR CHECKING NOT PROVIDED FOR ELSEWHERE
    • G07C3/00—Registering or indicating the condition or the working of machines or other apparatus, other than vehicles
    • G07C3/08—Registering or indicating the production of the machine either with or without registering working or idle time
    • G07C3/12—Registering or indicating the production of the machine either with or without registering working or idle time in graphical form
    • G—PHYSICS
    • G08—SIGNALLING
    • G08G—TRAFFIC CONTROL SYSTEMS
    • G08G1/00—Traffic control systems for road vehicles
    • G08G1/01—Detecting movement of traffic to be counted or controlled

Landscapes

  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • 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)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

Trihydroxypregnene-3,20-diones (I) and especially 11 beta, 17 alpha, 21-trihydroxy-15, 16 beta-methylene-pregnene (4)-(and pregna-1,4-diene)-3,20-dione, for use as anti-inflammatories. R6 and R9 independently are H, halogen, R17, R21 independently are OH or O-acyl; Z is CO or beta-CH2OH. Preparation of (I) and 1,2-dehydro-deriv. by numerous methods e.g. (a) microbiological 11-hydroxylation of (I) (Z=CH2); (b) 1,2-dehydrogenation of a cmpd. (I); (c) adding HOCl or HOBr to the 9,11-double bond a cmpd. (I) or its, 1,2-dehydro-derivs. (Z = HC). In an example 11 beta, 17 alpha-21-trihydroxy-15,16 beta-methylene-pregnene (4)-3,20-dione, m.p. 219-221 degrees is obtained by microbiological hydroxylation of 17 alpha, 21-dihydroxy-15,16 beta-methylene-pregnene (4)-3,20-dione using Coniothyrium hellebori as organism.

Description

       

  
 



  Verfahren zur Herstellung neuer Steroide der Pregnanreihe
Die Erfindung betrifft ein Verfahren zur Herstellung neuer Steroide der Formel
EMI1.1     
 in der R6 und   Rg    unabhängig voneinander Wasserstoff, Fluor, Chlor oder Brom, R17 Hydroxy oder Acyloxy und   R    Acyloxy bedeuten bzw. deren   1,2-Dehydroderivate.   



   Eine Acyloxygruppe enthält vorzugsweise den Rest einer gesättigten oder ungesättigten aliphatischen oder cycloaliphatischen, einer araliphatischen oder aromatischen Carbonsäure mit bis zu 20, vorzugsweise bis zu 12 C-Atomen. Beispiele solcher Säuren sind Ameisensäure, Essigsäure, Pivalinsäure, Propionsäure, Buttersäure, Capronsäure, Önanthsäure,   folsäure,    Palmitinsäure, Stearinsäure, Bernsteinsäure, Malonsäure, Fumarsäure, Zintronensäure, Cyclohexylpropionsäure, Phenylessigsäure und Benzoesäure.



   Das erfindungsgemässe Verfahren ist dadurch gekennzeichnet, dass man die   ll-Hydroxygruppe    eines Steroids der Formel Beispiel
2,0 g   2 1-Acetoxy-1 iss, 17-dihydroxy-15ss, 16ss-methylen-    pregn-4-en-3,20-dion wurden in 200 ml Aceton gelöst, auf
EMI1.2     
 in der   R6,      Rg,    R17 und R21 die obige Bedeutung haben, oder des entsprechenden 1,2-Dehydroderivats zur Ketogruppe oxydiert.



   Zur Herstellung der Ausgangsstoffe kann auf die belgische Patentschrift Nr. 760 392 verwiesen werden.



   Die erfindungsgemäss erhältlichen Steroide sind endocrin, insbesondere antiinflammatorisch, wirksam. Sie können als Heilmittel in Form pharmazeutischer Präparate Verwendung finden, welche sie in Mischung mit einem für die enterale, perkutane oder parenterale Applikation geeigneten pharmazeutischen, organischen oder anorganischen inerten Trägermaterial enthalten. Die pharmazeutischen Präparate können in fester Form, in halbfester oder in flüssiger Form vorliegen.



  Gegebenenfalls enthalten sie Hilfsstoffe, wie Konservierungs-, Stabilisierungs-, Netz- oder Emulgiermittel, Salze zur Ver änderung des osmotischen Druckes oder Puffer. Sie können auch noch andere therapeutisch wertvolle Stoffe enthalten.   0     abgekühlt und innert 5 Min. mit 1,7 ml 8n CrO3 in 2n   H2S04    (Jones-Reagens) und 20 ml Aceton versetzt. Es  wurde noch 10 Min. bei   0     gerührt, dann mit 4 ml Methanol versetzt und schliesslich das Reaktionsgemisch auf Eiswasser gegossen. Durch Extraktion mit Methylenchlorid extrahierte man 2,0 g Substanz, die auf der 50fachen Menge Silicagel chromatographiert wurde. 

  Mit Methylenchlorid-Aceton 9:1 eluierte man reines   21 -Acetoxy-17-hydroxy-15ss, 16ss-methy      len-pregn-4-en-3,1 1,20-trion,    Schmelzpunkt   259-261  .    



  
 



  Process for the production of new steroids of the Pregnan range
The invention relates to a process for the preparation of new steroids of the formula
EMI1.1
 in which R6 and Rg are independently hydrogen, fluorine, chlorine or bromine, R17 is hydroxy or acyloxy and R is acyloxy or their 1,2-dehydro derivatives.



   An acyloxy group preferably contains the residue of a saturated or unsaturated aliphatic or cycloaliphatic, an araliphatic or aromatic carboxylic acid having up to 20, preferably up to 12, carbon atoms. Examples of such acids are formic acid, acetic acid, pivalic acid, propionic acid, butyric acid, caproic acid, enanthic acid, folic acid, palmitic acid, stearic acid, succinic acid, malonic acid, fumaric acid, tintronic acid, cyclohexylpropionic acid, phenylacetic acid and benzoic acid.



   The process according to the invention is characterized in that the II-hydroxy group of a steroid of the formula Example
2.0 g of 2 1-acetoxy-1iss, 17-dihydroxy-15ss, 16ss-methylenepreg-4-en-3,20-dione were dissolved in 200 ml of acetone
EMI1.2
 in which R6, Rg, R17 and R21 have the above meaning, or the corresponding 1,2-dehydro derivative is oxidized to the keto group.



   For the preparation of the starting materials, reference can be made to Belgian patent specification No. 760 392.



   The steroids obtainable according to the invention are endocrine, in particular anti-inflammatory, effective. They can be used as remedies in the form of pharmaceutical preparations which they contain as a mixture with a pharmaceutical, organic or inorganic inert carrier material suitable for enteral, percutaneous or parenteral administration. The pharmaceutical preparations can be in solid, semi-solid or liquid form.



  They may contain auxiliaries such as preservatives, stabilizers, wetting agents or emulsifiers, salts for changing the osmotic pressure or buffers. They can also contain other therapeutically valuable substances. 0 and 1.7 ml of 8N CrO3 in 2N H2S04 (Jones reagent) and 20 ml of acetone were added within 5 minutes. The mixture was stirred at 0 for a further 10 minutes, then 4 ml of methanol were added and the reaction mixture was finally poured onto ice water. Extraction with methylene chloride was used to extract 2.0 g of substance, which was chromatographed on 50 times the amount of silica gel.

  Pure 21-acetoxy-17-hydroxy-15ss, 16ss-methylene-pregn-4-en-3,1 1,20-trione, melting point 259-261, was eluted with methylene chloride-acetone 9: 1.

Claims (1)

PATENTANSPRUCH Verfahren zur Herstellung neuer EMI2.1 <tb> Steroide <SEP> der <SEP> Formel <tb> <SEP> C111-2R21 <tb> <SEP> 0=0 <tb> <SEP> 0%t <SEP> 7 <tb> <SEP> 110 <SEP> 1 <tb> <SEP> 3 <tb> 0H <tb> <SEP> R6 <tb> in der R5 und Rg unabhängig voneinander Wasserstoff, Fluor, Chlor oder Brom, R17 Hydroxy oder Acyloxy und R21 Acvloxv bedeuten bzw. deren 1,2-Dehvdroderivate, dadurch gekennzeichnet, dass man die 11-Hydroxygruppe eines Steroids der Formel EMI2.2 oder des entsprechenden 1,2-Dehydroderivats zur Ketogruppe oxydiert. PATENT CLAIM Process for the production of new EMI2.1 <tb> Steroids <SEP> of the <SEP> formula <tb> <SEP> C111-2R21 <tb> <SEP> 0 = 0 <tb> <SEP> 0% t <SEP> 7 <tb> <SEP> 110 <SEP> 1 <tb> <SEP> 3 <tb> 0H <tb> <SEP> R6 <tb> in which R5 and Rg are independently hydrogen, fluorine, chlorine or bromine, R17 is hydroxy or acyloxy and R21 is acvloxy or their 1,2-dehydro derivatives, characterized in that the 11-hydroxy group of a steroid of the formula EMI2.2 or the corresponding 1,2-dehydro derivative is oxidized to the keto group.
CH860472A 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones CH531494A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CH860472A CH531494A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH860472A CH531494A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones
CH1883169A CH525872A (en) 1969-12-17 1969-12-17 Process for the production of new steroids of the Pregnan range

Publications (1)

Publication Number Publication Date
CH531494A true CH531494A (en) 1972-12-15

Family

ID=4435537

Family Applications (11)

Application Number Title Priority Date Filing Date
CH860372A CH531493A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones
CH1883169A CH525872A (en) 1969-12-17 1969-12-17 Process for the production of new steroids of the Pregnan range
CH860272A CH531492A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones
CH860172A CH531487A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones
CH859872A CH529734A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones
CH860072A CH531491A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones
CH860672A CH531486A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones
CH859772A CH531485A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones
CH860472A CH531494A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones
CH859972A CH531490A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones
CH860572A CH531495A (en) 1969-12-17 1970-10-30 Antiinflammatory pregnene-diones

Family Applications Before (8)

Application Number Title Priority Date Filing Date
CH860372A CH531493A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones
CH1883169A CH525872A (en) 1969-12-17 1969-12-17 Process for the production of new steroids of the Pregnan range
CH860272A CH531492A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones
CH860172A CH531487A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones
CH859872A CH529734A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones
CH860072A CH531491A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones
CH860672A CH531486A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones
CH859772A CH531485A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones

Family Applications After (2)

Application Number Title Priority Date Filing Date
CH859972A CH531490A (en) 1969-12-17 1969-12-17 Antiinflammatory pregnene-diones
CH860572A CH531495A (en) 1969-12-17 1970-10-30 Antiinflammatory pregnene-diones

Country Status (17)

Country Link
JP (1) JPS4920774B1 (en)
AT (8) AT316774B (en)
BE (1) BE760392A (en)
CA (1) CA955931A (en)
CH (11) CH531493A (en)
DE (1) DE2061183C3 (en)
ES (2) ES386503A1 (en)
FI (1) FI47484C (en)
FR (1) FR2081369B1 (en)
GB (1) GB1276419A (en)
HU (1) HU162802B (en)
IE (1) IE34816B1 (en)
IL (1) IL35790A (en)
NL (1) NL7016761A (en)
NO (1) NO135528C (en)
YU (1) YU34700B (en)
ZA (1) ZA708096B (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2740344A (en) * 1951-12-05 1956-04-03 Messrs Lumoprint Zindler K G Device for treating directly exposed photopapers
DE2453823C2 (en) * 1974-11-11 1984-08-09 Schering AG, 1000 Berlin und 4709 Bergkamen 11β, 17α-dihydroxy-15α, 16α-methylene-1,4-pregnadiene-3,20-dione
JPS56109115A (en) * 1980-12-05 1981-08-29 Fukui Kikai Kk Controlling method for feeder for strip material

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3438975A (en) * 1966-07-01 1969-04-15 Syntex Corp 15alpha,16alpha-methylene pregnanes and 19-nor-pregnanes
CH503720A (en) * 1968-04-22 1971-02-28 Hoffmann La Roche Hormone active steroids

Also Published As

Publication number Publication date
DE2061183B2 (en) 1979-05-23
NO135528C (en) 1977-04-20
ES403723A2 (en) 1975-05-01
IE34816L (en) 1971-06-17
CH531485A (en) 1972-12-15
JPS4920774B1 (en) 1974-05-27
HU162802B (en) 1973-04-28
AT315395B (en) 1974-05-27
CH531486A (en) 1972-12-15
CH525872A (en) 1972-07-31
BE760392A (en) 1971-06-16
CH531490A (en) 1972-12-15
DE2061183A1 (en) 1971-06-24
CH531491A (en) 1972-12-15
AT315396B (en) 1974-05-27
CH531492A (en) 1972-12-15
ES386503A1 (en) 1973-03-16
IL35790A0 (en) 1971-02-25
CH529734A (en) 1972-10-31
AT316774B (en) 1974-07-25
NL7016761A (en) 1971-06-21
YU298070A (en) 1979-07-10
CH531495A (en) 1972-12-15
CH531487A (en) 1972-12-15
AT316772B (en) 1974-07-25
FI47484B (en) 1973-08-31
FI47484C (en) 1973-12-10
IL35790A (en) 1974-05-16
NO135528B (en) 1977-01-10
AT308292B (en) 1973-06-25
CA955931A (en) 1974-10-08
AT316771B (en) 1974-07-25
AT315397B (en) 1974-05-27
DE2061183C3 (en) 1980-01-17
GB1276419A (en) 1972-06-01
ZA708096B (en) 1971-09-29
YU34700B (en) 1979-12-31
FR2081369A1 (en) 1971-12-03
CH531493A (en) 1972-12-15
AT316773B (en) 1974-07-25
FR2081369B1 (en) 1975-04-18
IE34816B1 (en) 1975-08-20

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