CH529734A - Antiinflammatory pregnene-diones - Google Patents
Antiinflammatory pregnene-dionesInfo
- Publication number
- CH529734A CH529734A CH859872A CH859872A CH529734A CH 529734 A CH529734 A CH 529734A CH 859872 A CH859872 A CH 859872A CH 859872 A CH859872 A CH 859872A CH 529734 A CH529734 A CH 529734A
- Authority
- CH
- Switzerland
- Prior art keywords
- beta
- acid
- pregnene
- methylene
- dione
- Prior art date
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 Wasserstoff, Fluor, Chlor oder Brom, Rg Chlor oder Brom und R17 und R21 unabhängig voneinander Hydroxy oder 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, Ölsäure, Palmitinsäure, Stearinsäure, Bernsteinsäure, Malonsäure, Fumarsäure, Zitronensäure, Cyclohexylpropionsäure, Phenylessigsäure und Benzoesäure.
Eine bevorzugte Gruppe von Verbindungen der Formel I sind diejenigen, in denen R6 Wasserstoff oder Fluor und R17 und R21 Hydroxy oder C1¯6-Alkanoyloxy darstellen.
Das erfindungsgemässe Verfahren ist dadurch gekennzeichnet, dass man an die 9,11-Doppelbindung einer Verbindung der Formel
EMI1.2
in der R6, R17 und R21 die obige Bedeutung haben, oder deren 1,2-Dehydroderivat unterchlorige oder unterbromige Säure anlagert.
Zweckmässig löst man das Ausgangssteroid in einem geeigneten Lösungsmittel, z. B. einem Äther, wie Tetrahydrofuran oder Dioxan, einem chlorierten Kohlenwasserstoff, wie Methylenchlorid oder Chloroform, oder einem Keton, wie Aceton und lässt unterchlorige bzw. unterbromige Säure einwirken. Die unterchlorige oder unterbromige Säure wird zweckmässig im Reaktionsgemisch selbst erzeugt; z. B. aus N-Brom oder N-Chloramiden oder -imiden, wie N-Chlorsuccinimid oder N-Bromacetamid und einer starken Säure, vorzugsweise Perchlorsäure.
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 z. B. 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 Form, oder in flüssiger Form, vorliegen. Gegebenenfalls enthalten sie Hilfsstoffe, wie Konservierungs-, Stabilisierungs-, Netz- oder Emulgiermittel, Salze zur Veränderung des osmotischen Druckes oder Puffer. Sie können auch noch andere therapeutisch wertvolle Stoffe enthalten.
Beispiel
Zu einer Lösung von 3,98 g 21-Acetoxy-17a-hydroxy 15,16ss-methylen-pregna-4,9(11)-dien-3,20-dion in 80 ml Dioxan werden 3 ml 0,5n Perchlorsäure und anschliessend innerhalb 30 Minuten 1,65 g N-Bromacetamid in drei Portionen zugegeben. Das Reaktionsgemisch wird 5 Stunden gerührt, auf 200 ml 5 %ige Natriumhydrogencarbonatlösung gegossen und mit Methylenchlorid extrahiert. Aufarbeiten des Extraktes liefert 21-Acetoxy-9a-brom- 11ss,17a-dihydroxyr 15,16ss-rnethylen-pregn-4-en-3,20-dion.
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 is hydrogen, fluorine, chlorine or bromine, Rg is chlorine or bromine and R17 and R21 are independently hydroxy or 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, oleic acid, palmitic acid, stearic acid, succinic acid, malonic acid, fumaric acid, citric acid, cyclohexylpropionic acid, phenylacetic acid and benzoic acid.
A preferred group of compounds of the formula I are those in which R6 is hydrogen or fluorine and R17 and R21 are hydroxy or C1 C16-alkanoyloxy.
The process according to the invention is characterized in that the 9,11 double bond of a compound of the formula
EMI1.2
in which R6, R17 and R21 have the above meaning, or their 1,2-dehydroderivative adds hypochlorous or hypobromous acid.
The starting steroid is expediently dissolved in a suitable solvent, e.g. B. an ether such as tetrahydrofuran or dioxane, a chlorinated hydrocarbon such as methylene chloride or chloroform, or a ketone such as acetone and allows hypochlorous or hypobromous acid to act. The hypochlorous or hypobromous acid is expediently generated in the reaction mixture itself; z. B. from N-bromine or N-chloramides or imides, such as N-chlorosuccinimide or N-bromoacetamide and a strong acid, preferably perchloric acid.
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. You can use as a remedy e.g. B. can be used in the form of pharmaceutical preparations which contain them 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 form, in semi-solid form, or in liquid form. They may contain auxiliaries, such as preservatives, stabilizers, wetting agents or emulsifiers, salts to change the osmotic pressure or buffers. They can also contain other therapeutically valuable substances.
example
To a solution of 3.98 g of 21-acetoxy-17a-hydroxy 15,16ss-methylene-pregna-4,9 (11) -diene-3,20-dione in 80 ml of dioxane, 3 ml of 0.5N perchloric acid and then 1.65 g of N-bromoacetamide were added in three portions within 30 minutes. The reaction mixture is stirred for 5 hours, poured onto 200 ml of 5% sodium hydrogen carbonate solution and extracted with methylene chloride. Working up the extract yields 21-acetoxy-9a-bromo-11ss, 17a-dihydroxyr 15,16ss-methylene-pregn-4-en-3,20-dione.
Claims (1)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH859872A CH529734A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH859872A CH529734A (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 |
---|---|
CH529734A true CH529734A (en) | 1972-10-31 |
Family
ID=4435537
Family Applications (11)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CH859772A CH531485A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
CH860472A CH531494A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
CH860172A CH531487A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
CH860672A CH531486A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
CH859972A CH531490A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
CH859872A CH529734A (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 |
CH860072A CH531491A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
CH860272A CH531492A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
CH860372A CH531493A (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 (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CH859772A CH531485A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
CH860472A CH531494A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
CH860172A CH531487A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
CH860672A CH531486A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
CH859972A CH531490A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
Family Applications After (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CH1883169A CH525872A (en) | 1969-12-17 | 1969-12-17 | Process for the production of new steroids of the Pregnan range |
CH860072A CH531491A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
CH860272A CH531492A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
CH860372A CH531493A (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) | AT316773B (en) |
BE (1) | BE760392A (en) |
CA (1) | CA955931A (en) |
CH (11) | CH531485A (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)
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)
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 |
-
1969
- 1969-12-17 CH CH859772A patent/CH531485A/en not_active IP Right Cessation
- 1969-12-17 CH CH860472A patent/CH531494A/en not_active IP Right Cessation
- 1969-12-17 CH CH860172A patent/CH531487A/en not_active IP Right Cessation
- 1969-12-17 CH CH860672A patent/CH531486A/en not_active IP Right Cessation
- 1969-12-17 CH CH859972A patent/CH531490A/en not_active IP Right Cessation
- 1969-12-17 CH CH859872A patent/CH529734A/en not_active IP Right Cessation
- 1969-12-17 CH CH1883169A patent/CH525872A/en not_active IP Right Cessation
- 1969-12-17 CH CH860072A patent/CH531491A/en not_active IP Right Cessation
- 1969-12-17 CH CH860272A patent/CH531492A/en not_active IP Right Cessation
- 1969-12-17 CH CH860372A patent/CH531493A/en not_active IP Right Cessation
-
1970
- 1970-10-30 CH CH860572A patent/CH531495A/en not_active IP Right Cessation
- 1970-11-14 IE IE1600/70A patent/IE34816B1/en unknown
- 1970-11-16 NL NL7016761A patent/NL7016761A/xx unknown
- 1970-11-26 FI FI703190A patent/FI47484C/en active
- 1970-11-30 ZA ZA708096*A patent/ZA708096B/en unknown
- 1970-12-02 HU HUHO1335A patent/HU162802B/hu unknown
- 1970-12-04 IL IL35790A patent/IL35790A/en unknown
- 1970-12-07 YU YU2980/70A patent/YU34700B/en unknown
- 1970-12-10 CA CA100,261A patent/CA955931A/en not_active Expired
- 1970-12-11 DE DE2061183A patent/DE2061183C3/en not_active Expired
- 1970-12-15 GB GB59497/70A patent/GB1276419A/en not_active Expired
- 1970-12-16 AT AT675572A patent/AT316773B/en not_active IP Right Cessation
- 1970-12-16 AT AT675372A patent/AT316772B/en not_active IP Right Cessation
- 1970-12-16 AT AT675772A patent/AT316774B/en active
- 1970-12-16 AT AT1130470A patent/AT308292B/en not_active IP Right Cessation
- 1970-12-16 AT AT675172A patent/AT315395B/en not_active IP Right Cessation
- 1970-12-16 BE BE760392A patent/BE760392A/en unknown
- 1970-12-16 AT AT675672A patent/AT315397B/en not_active IP Right Cessation
- 1970-12-16 AT AT675272A patent/AT316771B/en active
- 1970-12-16 FR FR7045351A patent/FR2081369B1/fr not_active Expired
- 1970-12-16 NO NO4845/70A patent/NO135528C/no unknown
- 1970-12-16 ES ES386503A patent/ES386503A1/en not_active Expired
- 1970-12-16 JP JP45111944A patent/JPS4920774B1/ja active Pending
- 1970-12-16 AT AT675472A patent/AT315396B/en not_active IP Right Cessation
-
1972
- 1972-06-10 ES ES403723A patent/ES403723A2/en not_active Expired
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PL | Patent ceased |