DE1063164B - Process for the preparation of an anti-inflammatory steroid compound - Google Patents
Process for the preparation of an anti-inflammatory steroid compoundInfo
- Publication number
- DE1063164B DE1063164B DEU4762A DEU0004762A DE1063164B DE 1063164 B DE1063164 B DE 1063164B DE U4762 A DEU4762 A DE U4762A DE U0004762 A DEU0004762 A DE U0004762A DE 1063164 B DE1063164 B DE 1063164B
- Authority
- DE
- Germany
- Prior art keywords
- methyl
- dione
- pregnadiene
- ecm
- dioxy
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 12
- 150000001875 compounds Chemical class 0.000 title claims description 8
- 239000002260 anti-inflammatory agent Substances 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N methyl pentane Natural products CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- -1 hexane hydrocarbons Chemical class 0.000 claims description 5
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 229930195733 hydrocarbon Natural products 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 3
- 239000000284 extract Substances 0.000 claims description 3
- 239000003862 glucocorticoid Substances 0.000 claims description 3
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims description 3
- 235000019345 sodium thiosulphate Nutrition 0.000 claims description 3
- 239000004593 Epoxy Substances 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 238000001953 recrystallisation Methods 0.000 claims description 2
- 235000009518 sodium iodide Nutrition 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims 2
- 238000006243 chemical reaction Methods 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 235000017557 sodium bicarbonate Nutrition 0.000 claims 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims 1
- 229920002527 Glycogen Polymers 0.000 claims 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 claims 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims 1
- 229930006000 Sucrose Natural products 0.000 claims 1
- OPDQOKREXYCJHD-YUMYIRISSA-N [(1r,4ar,5r,8ar)-4a-formyl-5-[2-(furan-3-yl)ethyl]-1-methyl-6-methylidene-3,4,5,7,8,8a-hexahydro-2h-naphthalen-1-yl]methyl acetate Chemical compound C([C@H]1[C@]2(C=O)CCC[C@@]([C@H]2CCC1=C)(C)COC(=O)C)CC=1C=COC=1 OPDQOKREXYCJHD-YUMYIRISSA-N 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 239000003242 anti bacterial agent Substances 0.000 claims 1
- 229940088710 antibiotic agent Drugs 0.000 claims 1
- 239000007900 aqueous suspension Substances 0.000 claims 1
- 230000009286 beneficial effect Effects 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 239000006071 cream Substances 0.000 claims 1
- 239000013078 crystal Substances 0.000 claims 1
- 230000008021 deposition Effects 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 238000001035 drying Methods 0.000 claims 1
- 230000008030 elimination Effects 0.000 claims 1
- 238000003379 elimination reaction Methods 0.000 claims 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 claims 1
- 229940096919 glycogen Drugs 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 150000002430 hydrocarbons Chemical class 0.000 claims 1
- 229910000040 hydrogen fluoride Inorganic materials 0.000 claims 1
- 239000012433 hydrogen halide Substances 0.000 claims 1
- 229910000039 hydrogen halide Inorganic materials 0.000 claims 1
- 229910052740 iodine Inorganic materials 0.000 claims 1
- 239000011630 iodine Substances 0.000 claims 1
- 235000015110 jellies Nutrition 0.000 claims 1
- 239000008101 lactose Substances 0.000 claims 1
- XCOBTUNSZUJCDH-UHFFFAOYSA-B lithium magnesium sodium silicate Chemical compound [Li+].[Li+].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Na+].[Na+].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3.O1[Si](O2)([O-])O[Si]3([O-])O[Si]1([O-])O[Si]2([O-])O3 XCOBTUNSZUJCDH-UHFFFAOYSA-B 0.000 claims 1
- 210000004185 liver Anatomy 0.000 claims 1
- 239000006210 lotion Substances 0.000 claims 1
- 230000014759 maintenance of location Effects 0.000 claims 1
- 230000008018 melting Effects 0.000 claims 1
- 238000002844 melting Methods 0.000 claims 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims 1
- 230000007935 neutral effect Effects 0.000 claims 1
- 239000002674 ointment Substances 0.000 claims 1
- 229940057838 polyethylene glycol 4000 Drugs 0.000 claims 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims 1
- 239000011541 reaction mixture Substances 0.000 claims 1
- 238000010992 reflux Methods 0.000 claims 1
- PODWXQQNRWNDGD-UHFFFAOYSA-L sodium thiosulfate pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].[O-]S([S-])(=O)=O PODWXQQNRWNDGD-UHFFFAOYSA-L 0.000 claims 1
- 238000003756 stirring Methods 0.000 claims 1
- 239000005720 sucrose Substances 0.000 claims 1
- 229940124530 sulfonamide Drugs 0.000 claims 1
- 150000003456 sulfonamides Chemical class 0.000 claims 1
- 239000000829 suppository Substances 0.000 claims 1
- 229940037128 systemic glucocorticoids Drugs 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- QQCBOIWDENXRLP-BYZMTCBYSA-N (8s,9s,10r,13r,14s,17s)-17-ethyl-10,13-dimethyl-6,7,8,9,11,12,14,15,16,17-decahydro-3h-cyclopenta[a]phenanthrene Chemical class C1CC2=CCC=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](CC)[C@@]1(C)CC2 QQCBOIWDENXRLP-BYZMTCBYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- ZESRJSPZRDMNHY-YFWFAHHUSA-N 11-deoxycorticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 ZESRJSPZRDMNHY-YFWFAHHUSA-N 0.000 description 1
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical compound C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 208000029422 Hypernatremia Diseases 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- ZESRJSPZRDMNHY-UHFFFAOYSA-N de-oxy corticosterone Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 ZESRJSPZRDMNHY-UHFFFAOYSA-N 0.000 description 1
- 229940119740 deoxycorticosterone Drugs 0.000 description 1
- FGRVOLIFQGXPCT-UHFFFAOYSA-L dipotassium;dioxido-oxo-sulfanylidene-$l^{6}-sulfane Chemical compound [K+].[K+].[O-]S([O-])(=O)=S FGRVOLIFQGXPCT-UHFFFAOYSA-L 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- DJEHXEMURTVAOE-UHFFFAOYSA-M potassium bisulfite Chemical compound [K+].OS([O-])=O DJEHXEMURTVAOE-UHFFFAOYSA-M 0.000 description 1
- 229940099427 potassium bisulfite Drugs 0.000 description 1
- 235000010259 potassium hydrogen sulphite Nutrition 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Description
Gegenstand der Erfindung ist ein Verfahren zur Herstellung einer entzündungswidrig wirkenden Steroidverbindung, nämlich von 6 - Methyl - Ιίβ,Πα - dioxyl,4-pregnadien-3,20-dion aus 6-Methyl-l 17 a-dioxy-21-jod-l ,4-pregnadien-3,20-dion.The invention relates to a process for the production of an anti-inflammatory steroid compound, namely 6-methyl- Ιίβ, Πα- dioxyl, 4-pregnadiene-3,20-dione from 6-methyl-l 17 a-dioxy-21-iodine-l , 4-pregnadiene-3,20-dione.
Zur Durchführung des erfindungsgemäßen Verfahrens wird 6 - Methyl -11/?, 17a- dioxy -21-jod-l,4- pr egnadien-3,20-dion mit einem Reduktionsmittel, wie Natriumthiosulfat, Kaliumthiosulfat, Natriumbisulfit, Kaliumbisulfit od. dgl., in einem wäßrigen organischen Lösungsmittel zu 6-Methyl-l 1 ß, 17 a-dioxy-1,4-pregnadien-3,20-dion umgesetzt.To carry out the process according to the invention, 6-methyl-11 / ?, 17a-dioxy -21-iodine-1,4-pregnadiene-3,20-dione is added with a reducing agent such as sodium thiosulfate, potassium thiosulfate, sodium bisulfite, potassium bisulfite or the like. , implemented in an aqueous organic solvent to 6-methyl-l 1 ß, 17 a-dioxy-1,4-pregnadiene-3,20-dione.
Man geht dabei so vor, daß man das 6-Methyl-l Iß, 17a-dioxy-21-jod-l,4-pregnadien-3,20-dion z. B. in Essigsäure aufschlämmt, eine wäßrige Lösung aus Natriumthiosulfat od. dgl. zufügt und das erhaltene Gemisch 10 Minuten bis 2 Stunden bei Zimmertemperatur rührt. Das Reaktionsprodukt wird aus dem wäßrigen Gemisch nach üblichen Verfahren, z. B. durch Filtrieren, oder durch Extrahieren mit einem organischen, mit Wasser nicht mischbaren Lösungsmittel, wie Äther, Benzol, Methylenchlorid, Äthylenchlorid, Tetrachlorkohlenstoff, Chloroform, Hexan, Heptan od. dgl. und anschließendes Eindampfen der Extrakte isoliert. Das gewonnene 6-Methyl-ll/?,17a-dioxy-l,4-pregnadien-3,20-dion wird darauf in bekannter Weise, z. B. durch UmkristalHsieren aus Äther, Aceton, Methanol, Äthanol, Hexankohlenwasserstoffen oder aus Gemischen dieser Lösungsmittel oder auf chromatographischem Wege gereinigt. Es kann anschließend in ebenfaUs bekannter Weise z. B. in Essigsäure mit Chromsäureanhydrid oder in Pyridin, Dioxan oder einem anderen Lösungsmittel zum 6-Methyl-l 7 a-oxyl,4-pregnadien-3,ll,20-trion oxydiert werden.The procedure is that the 6-methyl-l Iß, 17a-dioxy-21-iodine-1,4-pregnadiene-3,20-dione z. B. slurried in acetic acid, an aqueous solution of sodium thiosulfate or the like. Adds and the mixture obtained is stirred for 10 minutes to 2 hours at room temperature. The reaction product is extracted from the aqueous mixture by conventional methods, e.g. B. by filtration, or by extracting with an organic, water-immiscible solvent such as ether, benzene, methylene chloride, ethylene chloride, carbon tetrachloride, chloroform, hexane, heptane or the like. And then evaporating the extracts. The obtained 6-methyl-II / ?, 17a-dioxy-l, 4-pregnadiene-3,20-dione is then in a known manner, for. B. purified by recrystallization from ether, acetone, methanol, ethanol, hexane hydrocarbons or from mixtures of these solvents or by chromatography. It can then be used in a known manner, for. B. in acetic acid with chromic anhydride or in pyridine, dioxane or another solvent to 6-methyl-l 7 a-oxyl, 4-pregnadiene-3, ll, 20-trione are oxidized.
Das für das erfindungsgemäße Verfahren als Ausgangsstoff verwendete 6-Methyl-llß,17a-dioxy-21-jod-l,4-pregnadien-3,20-dion kann in der Weise erhalten werden, daß man ll^,17a,21-Trioxy-4-pregnen-3,20-dion-3,20-bisketal z. B. mit Perbenzoesäure in das entsprechende 5<x,6a-Epoxyd überführt, dieses mit einem Grignard-Reagenz in 6-Methyl-5α,ίίβ,Πα,2ί-tetraoxy-pregnan-3,20-dion-3,20-bis-ketal umwandelt, die erhaltene Verbindung durch saure Hydrolyse entketahsiert, das gebildete 6 - Methyl - 5a, 11/?, 17a, 21 - tetraoxy - pregnan-3,20-dion unter Ausschluß von Sauerstoff in 4(5)-Stellung dehydratisiert, das erhaltene 6-Methyl-l iß, 17 a,21-trioxy-4-pregnen-3,20-dion auf mikrobiologischem Wege in 1 (2)-Steilung dehydriert, das so hergestellte 1,4-Pregnadienderivat mit einem organischen Sulfonsäurehalogenid behandelt und das gebildete 21-Sulfonat mit Natriumiodid in Acetonlösung umsetzt.The 6-methyl-11ß, 17a-dioxy-21-iodo-1,4-pregnadiene-3,20-dione used as starting material for the process according to the invention can be obtained in such a way that 11 ^, 17a, 21-trioxy -4-pregnen-3,20-dione-3,20-bisketal e.g. B. with perbenzoic acid in the corresponding 5 <x, 6a-epoxy, this with a Grignard reagent in 6-methyl-5 α, ίίβ, Πα, 2ί -tetraoxy -pregnane-3,20-dione-3,20- bis-ketal is converted, the compound obtained is de-ketahsed by acid hydrolysis, the 6-methyl-5a, 11 / ?, 17a, 21-tetraoxy-pregnane-3,20-dione formed is dehydrated in the 4 (5) position with the exclusion of oxygen , the 6-methyl-l iß, 17 a, 21-trioxy-4-pregnen-3,20-dione obtained is microbiologically dehydrated in 1 (2) division, the 1,4-pregnadiene derivative thus produced with an organic sulfonic acid halide treated and the 21-sulfonate formed is reacted with sodium iodide in acetone solution.
Das neue 6-Methyl-ll/?,17a-dioxy-l,4-pregnadien-3,20-dion besitzt hohe physiologische Wirksamkeit,
ebenso sein 11-Keto-Analoges. Ihre Wirkungsspektren unterscheiden sich insbesondere hinsichtlich der Wirkung
Verfahren zur Herstellung
einer entzündungswidrig wirkenden
SteroidverbindungThe new 6-methyl-II / ?, 17a-dioxy-1,4-pregnadiene-3,20-dione has high physiological effectiveness, as does its 11-keto analogue. Their activity spectra differ in particular with regard to the method of production
an anti-inflammatory
Steroid compound
Anmelder:
The Upjohn Company,
Kalamazoo, Mich.. (V. St. A.)Applicant:
The Upjohn Company,
Kalamazoo, Mich .. (V. St. A.)
Vertreter:Representative:
Dr. W. Beil und A. Hoeppener, Rechtsanwälte,
Frankfurt/M.-Höchst, Antoniterstr. 36Dr. W. Beil and A. Hoeppener, lawyers,
Frankfurt / M.-Höchst, Antoniterstr. 36
Beanspruchte Priorität:
V. St. v. Amerika vom 10. September und 23. November 1956Claimed priority:
V. St. v. America September 10th and November 23rd, 1956
Frank Harris Lincoln jun., William Paul Schneider
und George Basil Spero, Kalamazoo, Mich. (V. St. A.), sind als Erfinder genannt wordenFrank Harris Lincoln Jr., William Paul Schneider
and George Basil Spero, Kalamazoo, Mich. (V. St. A.) have been named as inventors
auf den Mineral- und Wasser-Stoffwechsel von denen natürlich vorkommender Nebennierenrindenhormone. Sie verursachen eine erhöhte Salz- und Wasserausscheidung und sind daher für die Behandlung von chronischen kongestiven Herzfehlern, von Lebercirrhose, nephrotischem Syndrom, Eklampsie und Präeklampsie von besonderer Bedeutung. Sie besitzen ferner entzündungswidrige, glucocorticoide, anästhetisierende, uterine, ovarial- und adrenal-wachstumshemmende sowie adrenocorticoide Wirksamkeit. Besonders bemerkenswert ist ihre Wirkung gegen Entzündungen, bei gleichzeitig geringer Salzretention, wie aus den nachfolgenden, tabellarisch zusammengestellten Ergebnissen von Vergleichsversuchen hervorgeht, bei denen Hydrocortison und Desoxycorticosteron, deren Wirksamkeit mit 100 % angenommen wurde, als Vergleichssubstanzen dienten.on the mineral and water metabolism of those of naturally occurring adrenal cortex hormones. she cause increased salt and water excretion and are therefore used in the treatment of chronic congestive heart disease, cirrhosis of the liver, nephrotic syndrome, eclampsia and preeclampsia of special meaning. They also have anti-inflammatory, glucocorticoid, anesthetic, uterine, ovarian and adrenal growth-inhibiting as well as adrenocorticoid effectiveness. It is particularly noteworthy their anti-inflammatory effect, with low salt retention at the same time, as can be seen in the following, The tabular results of comparative experiments in which hydrocortisone and deoxycorticosterone, the effectiveness of which was assumed to be 100%, served as comparison substances.
909 607/429909 607/429
Claims (2)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1063164XA | 1956-09-10 | 1956-09-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1063164B true DE1063164B (en) | 1959-08-13 |
Family
ID=22310739
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEU4762A Pending DE1063164B (en) | 1956-09-10 | 1957-08-29 | Process for the preparation of an anti-inflammatory steroid compound |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1063164B (en) |
-
1957
- 1957-08-29 DE DEU4762A patent/DE1063164B/en active Pending
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