CH531492A - Antiinflammatory pregnene-diones - Google Patents
Antiinflammatory pregnene-dionesInfo
- Publication number
- CH531492A CH531492A CH860272A CH860272A CH531492A CH 531492 A CH531492 A CH 531492A CH 860272 A CH860272 A CH 860272A CH 860272 A CH860272 A CH 860272A CH 531492 A CH531492 A CH 531492A
- Authority
- CH
- Switzerland
- Prior art keywords
- beta
- pregnene
- acid
- methylene
- dione
- Prior art date
Links
- 230000003110 anti-inflammatory effect Effects 0.000 title abstract description 3
- 238000000034 method Methods 0.000 claims abstract description 6
- 150000003431 steroids Chemical class 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- MALIONKMKPITBV-UHFFFAOYSA-N 2-(3-chloro-4-hydroxyphenyl)-n-[2-(4-sulfamoylphenyl)ethyl]acetamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1CCNC(=O)CC1=CC=C(O)C(Cl)=C1 MALIONKMKPITBV-UHFFFAOYSA-N 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 3
- 238000005805 hydroxylation reaction Methods 0.000 abstract 2
- 230000002906 microbiologic effect Effects 0.000 abstract 2
- QYLWKJIGHRLVNZ-WHYACLPYSA-N (8R,9S,10S,13S,14S)-10,13-dimethyl-17-(2,2,2-trihydroxyacetyl)-1,2,4,5,6,7,8,9,11,12,14,15-dodecahydrocyclopenta[a]phenanthren-3-one Chemical class OC(C(C1=CC[C@H]2[C@@H]3CCC4CC(CC[C@]4(C)[C@H]3CC[C@]12C)=O)=O)(O)O QYLWKJIGHRLVNZ-WHYACLPYSA-N 0.000 abstract 1
- 241001312183 Coniothyrium Species 0.000 abstract 1
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract 1
- 239000002260 anti-inflammatory agent Substances 0.000 abstract 1
- 238000006356 dehydrogenation reaction Methods 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- 230000033444 hydroxylation Effects 0.000 abstract 1
- CUILPNURFADTPE-UHFFFAOYSA-N hypobromous acid Chemical compound BrO CUILPNURFADTPE-UHFFFAOYSA-N 0.000 abstract 1
- QWPPOHNGKGFGJK-UHFFFAOYSA-N hypochlorous acid Chemical compound ClO QWPPOHNGKGFGJK-UHFFFAOYSA-N 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- VAJVDSVGBWFCLW-UHFFFAOYSA-N 3-Phenyl-1-propanol Chemical compound OCCCC1=CC=CC=C1 VAJVDSVGBWFCLW-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- HJZLEGIHUQOJBA-UHFFFAOYSA-N cyclohexane propionic acid Chemical compound OC(=O)CCC1CCCCC1 HJZLEGIHUQOJBA-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003279 phenylacetic acid Substances 0.000 description 1
- 229960003424 phenylacetic acid Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- JWMFYGXQPXQEEM-WZBAXQLOSA-N pregnane Chemical compound C1CC2CCCC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](CC)[C@@]1(C)CC2 JWMFYGXQPXQEEM-WZBAXQLOSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (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, R21 Hydroxy oder Acyloxy und Z Carbonyl oder ss-Hydroxymethylen 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, Zintronensäure, Cyclohexylpropionsäure, Phenylessigsäure und Benzoesäure.
Bevorzugte erfindungsgemäss erhältliche Verbindungen sind diejenigen, in denen R6 und R9 Wasserstoff oder Fluor, R21 Hydroxy und Z ,B-Hydroxymethylen darstellen.
Das erfindungsgemässe Verfahren ist dadurch gekennzeichnet, dass man ein Steroid der Formel
EMI1.2
worin R6, R9 und Z die obige Bedeutung besitzen und Ac einen Acylrest darstellt, oder das 1,2-Dehydroderivat eines solchen Steroids mindestens in der Stellung 17a verseift.
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 Veränderung des osmotischen Druckes oder Puffer.
Sie können auch noch andere therapeutisch wertvolle Stoffe enthalten.
Beispiel 1
300 mg 17a,21-Diacetoxy-l l-hydroxy-15ss,16P-methy- len-pregn-4-en-3,20-dion wurden in 30 ml Methanol gelöst und mit 150 mg NaHCO3 6 Stunden bei Raumtemperatur gerührt. Zur Aufarbeitung wurde auf Eiswasser gegossen und mit Methylenchlorid extrahiert. Der organische Extrakt wurde mit Wasser neutral gewaschen, mit Na2SO4 getrocknet und im Vakuum eingedampft. Der Rückstand wurde auf 30 g Silicagel chromatographiert. Mit Benzol-Propanol (95 :5) wurde zunächst reines 2 1-Acetoxy- 11ss, 17a-dihydroxy- lSss,16ss-methylen-pregn-4-en-3,20-dion eluiert. Die nachfolgenden Fraktionen lieferten llss,17a,21-Trihydroxy- 15ss,16ss-methylen-pregn-4-en-3,20-dion, Smp. 218-220" C.
Beispiel 2
921 mg 21-Acetoxy-17-hydroxy-lSss,16ss-methylen-pregn- 4-en-3,11,20-trion und 46 mg Kaliumcarbonat wurden in 25 ml Methanol gelöst und 2 Stunden bei Raumtemperatur gerührt. Zur Aufarbeitung goss man auf Eiswasser und extrahierte mit Methylenchlorid. Durch Neutralwaschen mit Wasser, Trocknen mit Na2SO4 und Eindampfen des Lösungsmittels im Vakuum wurden aus dem organischen Extrakt 863 mg Rohprodukt erhalten. Dieses wurde auf Silicagel chromatographiert. Mit Benzol-Propanol (9: 1) wurde reines 17,21-Dihydroxy-lSss,16ss-methylen-pregn-4-en-3,11,20-trion isoliert. Schmelzpunkt 217O (Zers.). [a]D25 = + 180 (c=0,1 in Dioxan).
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 independently of one another are hydrogen, fluorine, chlorine or bromine, R21 is hydroxy or acyloxy and Z is carbonyl or ß-hydroxymethylene or 1,2 dehydro derivatives thereof.
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, tintronic acid, cyclohexylpropionic acid, phenylacetic acid and benzoic acid.
Preferred compounds obtainable according to the invention are those in which R6 and R9 are hydrogen or fluorine, R21 is hydroxy and Z, B-hydroxymethylene.
The method according to the invention is characterized in that a steroid of the formula
EMI1.2
where R6, R9 and Z have the above meaning and Ac is an acyl radical, or the 1,2-dehydro derivative of such a steroid is saponified at least in the 17a position.
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 to change the osmotic pressure or buffers.
They can also contain other therapeutically valuable substances.
example 1
300 mg of 17a, 21-diacetoxy-11-hydroxy-15ss, 16P-methylene-pregn-4-en-3,20-dione were dissolved in 30 ml of methanol and stirred with 150 mg of NaHCO3 for 6 hours at room temperature. For work-up, it was poured onto ice-water and extracted with methylene chloride. The organic extract was washed neutral with water, dried with Na2SO4 and evaporated in vacuo. The residue was chromatographed on 30 g of silica gel. With benzene-propanol (95: 5), pure 2 1-acetoxy-11ss, 17a-dihydroxy-lSss, 16ss-methylen-pregn-4-en-3,20-dione was first eluted. The following fractions yielded 11ss, 17a, 21-trihydroxy-15ss, 16ss-methylen-pregn-4-en-3,20-dione, m.p. 218-220 "C.
Example 2
921 mg of 21-acetoxy-17-hydroxy-lSss, 16ss-methylene-pregn-4-en-3,11,20-trione and 46 mg of potassium carbonate were dissolved in 25 ml of methanol and stirred for 2 hours at room temperature. For work-up, it was poured into ice water and extracted with methylene chloride. By washing neutral with water, drying with Na2SO4 and evaporating the solvent in vacuo, 863 mg of crude product were obtained from the organic extract. This was chromatographed on silica gel. With benzene-propanol (9: 1), pure 17,21-dihydroxy-lSss, 16ss-methylene-pregn-4-ene-3,11,20-trione was isolated. Melting point 2170 (dec.). [a] D25 = +180 (c = 0.1 in dioxane).
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH860272A CH531492A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH860272A CH531492A (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 |
|---|---|
| CH531492A true CH531492A (en) | 1972-12-15 |
Family
ID=4435537
Family Applications (11)
| 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 |
| CH860472A CH531494A (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 |
| CH860372A CH531493A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
| CH859872A CH529734A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
| CH860272A CH531492A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
| CH860072A CH531491A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
| CH860172A CH531487A (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 (6)
| 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 |
| CH860472A CH531494A (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 |
| CH860372A CH531493A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
| CH859872A CH529734A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
Family Applications After (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH860072A CH531491A (en) | 1969-12-17 | 1969-12-17 | Antiinflammatory pregnene-diones |
| CH860172A CH531487A (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 |
Country Status (17)
| Country | Link |
|---|---|
| JP (1) | JPS4920774B1 (en) |
| AT (8) | AT315396B (en) |
| BE (1) | BE760392A (en) |
| CA (1) | CA955931A (en) |
| CH (11) | CH525872A (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 CH1883169A patent/CH525872A/en not_active IP Right Cessation
- 1969-12-17 CH CH860472A patent/CH531494A/en not_active IP Right Cessation
- 1969-12-17 CH CH860672A patent/CH531486A/en not_active IP Right Cessation
- 1969-12-17 CH CH859772A patent/CH531485A/en not_active IP Right Cessation
- 1969-12-17 CH CH860372A patent/CH531493A/en not_active IP Right Cessation
- 1969-12-17 CH CH859872A patent/CH529734A/en not_active IP Right Cessation
- 1969-12-17 CH CH860272A patent/CH531492A/en not_active IP Right Cessation
- 1969-12-17 CH CH860072A patent/CH531491A/en not_active IP Right Cessation
- 1969-12-17 CH CH860172A patent/CH531487A/en not_active IP Right Cessation
- 1969-12-17 CH CH859972A patent/CH531490A/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 AT675472A patent/AT315396B/en not_active IP Right Cessation
- 1970-12-16 AT AT1130470A patent/AT308292B/en not_active IP Right Cessation
- 1970-12-16 ES ES386503A patent/ES386503A1/en not_active Expired
- 1970-12-16 JP JP45111944A patent/JPS4920774B1/ja active Pending
- 1970-12-16 BE BE760392A patent/BE760392A/en unknown
- 1970-12-16 AT AT675572A patent/AT316773B/en not_active IP Right Cessation
- 1970-12-16 AT AT675672A patent/AT315397B/en not_active IP Right Cessation
- 1970-12-16 AT AT675372A patent/AT316772B/en not_active IP Right Cessation
- 1970-12-16 FR FR7045351A patent/FR2081369B1/fr not_active Expired
- 1970-12-16 NO NO4845/70A patent/NO135528C/no unknown
- 1970-12-16 AT AT675272A patent/AT316771B/en active
- 1970-12-16 AT AT675172A patent/AT315395B/en not_active IP Right Cessation
- 1970-12-16 AT AT675772A patent/AT316774B/en active
-
1972
- 1972-06-10 ES ES403723A patent/ES403723A2/en not_active Expired
Also Published As
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |