DE1543247B - 16 beta methyl 9 alpha fluor 11 beta, 17alpha, 21 tnhydroxy 1,4 pregnadiene 3,20 dione 21 acetate or the corresponding alcohol and process for their production - Google Patents
16 beta methyl 9 alpha fluor 11 beta, 17alpha, 21 tnhydroxy 1,4 pregnadiene 3,20 dione 21 acetate or the corresponding alcohol and process for their productionInfo
- Publication number
- DE1543247B DE1543247B DE1543247B DE 1543247 B DE1543247 B DE 1543247B DE 1543247 B DE1543247 B DE 1543247B
- Authority
- DE
- Germany
- Prior art keywords
- acetate
- dione
- methyl
- beta
- pregnadiene
- 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
- 230000000875 corresponding Effects 0.000 title claims description 7
- 238000000034 method Methods 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title claims description 3
- QIEPWCSVQYUPIY-LEKSSAKUSA-N Delta(1)-progesterone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 QIEPWCSVQYUPIY-LEKSSAKUSA-N 0.000 title 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 title 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 title 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- JLTDJTHDQAWBAV-UHFFFAOYSA-N Dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- JYGXADMDTFJGBT-VWUMJDOOSA-N Cortisol 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 8
- 229960000890 hydrocortisone Drugs 0.000 description 8
- 150000003431 steroids Chemical class 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N acetic acid ethyl ester Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N HCl Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 206010018691 Granuloma Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 230000003110 anti-inflammatory Effects 0.000 description 3
- 235000009161 Espostoa lanata Nutrition 0.000 description 2
- 240000001624 Espostoa lanata Species 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M Sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L Sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 229960002537 betamethasone Drugs 0.000 description 2
- AKUJBENLRBOFTD-QZIXMDIESA-N betamethasone acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(C)=O)(O)[C@@]1(C)C[C@@H]2O AKUJBENLRBOFTD-QZIXMDIESA-N 0.000 description 2
- 229960004648 betamethasone acetate Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229960005205 prednisolone Drugs 0.000 description 2
- 229940116904 ANTIINFLAMMATORY THERAPEUTIC RADIOPHARMACEUTICALS Drugs 0.000 description 1
- 206010003246 Arthritis Diseases 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N Betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 1
- 229940074726 OPHTHALMOLOGIC ANTIINFLAMMATORY AGENTS Drugs 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M Potassium bicarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N Prednisolone Chemical compound O=C1C=C[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 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- -1 S-methyl steroids Chemical class 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- 230000001919 adrenal Effects 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 230000001054 cortical Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atoms Chemical group [H]* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 230000010925 negative regulation of granuloma formation Effects 0.000 description 1
- 229940094025 potassium bicarbonate Drugs 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 231100000486 side effect Toxicity 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229940075581 sodium bromide Drugs 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 210000001519 tissues Anatomy 0.000 description 1
Description
Gegenstand der Erfindung sind 16/?-Methyl-9a-fluor-1 l/?,17a,21 - trihydroxy - 1,4 - pregnadien - 3,20 - dion-21-acetat und der entsprechende 21-Alkohol. Diese neuen Verbindungen lassen sich durch die Strukturformel The invention relates to 16 /? - methyl-9a-fluoro-1 l / ?, 17a, 21 - trihydroxy - 1,4 - pregnadiene - 3.20 - dione-21-acetate and the corresponding 21 alcohol. These new compounds can be expressed by the structural formula
CH2ORCH 2 OR
COCO
HOHO
IOIO
darstellen, in der R Wasserstoff oder Acetyl bedeutet.represent, in which R is hydrogen or acetyl.
Ein weiterer Gegenstand der Erfindung ist ein Verfahren zur Herstellung dieser Verbindungen, das dadurch gekennzeichnet ist, daß man ein 16,5-Methyl-9a - fluor -11 /S, 17a,21 - trihydroxy - pregnan - 3,20 - dion-21-acetat mit Brom in an sich bekannter Weise umsetzt, das so erhaltene 16/?-Methyl-2,4-dibrom-9a-fluor-11 ß, 17a,21 - trihydroxy - pregnan - 3,20 - dion - 21 - acetat mit Dimethylformamid und Dimethylanilin behandelt, und das erhaltene zlU4-21-acetat gegebenenfalls nach an sich bekannten Methoden zu dem entsprechenden 21-Alkohol hydrolysiert.The invention also provides a process for the preparation of these compounds, which is characterized in that a 16,5-methyl-9a-fluoro-11 / S, 17a, 21-trihydroxy-pregnane-3.20-dione-21 -acetate is reacted with bromine in a manner known per se, the 16 /? - methyl-2,4-dibromo-9a-fluoro-11ß , 17a, 21-trihydroxy-pregnane-3.20-dione-21-acetate treated with dimethylformamide and dimethylaniline, and the zl U4 -21-acetate obtained is optionally hydrolyzed to the corresponding 21-alcohol by methods known per se.
Die für das erfindungsgemäße Verfahren verwendete Ausgangsverbindung, 16/?-Methyl-9a-fluor-1 Iß, 17α,21-trihydroxy-pregnan-3,20-dion-21-acetat, kann aus 16/3- Methyl -9a- fluor- ΙΙβ,Πα,ΙΙ- trihydroxy-4-pregnen-3,20-dion-21-acetat durch Hydrierung in Methanol mit einem Palladium-Kohlenstoff-Katalysator nach der Arbeitsweise hergestellt werden, die in Journal Amer. Chem. Soc. 77 (1955), S. 3166 und 3167 für die entsprechenden 16-Nor-Homologa beschrieben ist. Das 16/3-Methyl-9a-fluor-11 ß, 17a,21 -trihydroxy-4-pregnen-3,20-dion-21-acetat wiederum kann nach Beispiel 25 der Offenlegungsschrift 1 418 318 hergestellt werden. The starting compound used for the process according to the invention, 16/3-methyl-9a-fluoro-1 Iß, 17α, 21-trihydroxy-pregnane-3,20-dione-21-acetate, can be prepared from 16/3-methyl-9a-fluoro - ΙΙβ, Πα, ΙΙ- trihydroxy-4-pregnen-3,20-dione-21-acetate are prepared by hydrogenation in methanol with a palladium-carbon catalyst according to the procedure described in Journal Amer. Chem. Soc. 77 (1955), pp. 3166 and 3167 for the corresponding 16-Nor homologues. The 16/3-methyl-9a-fluoro- 11β, 17a, 21-trihydroxy-4-pregnen-3,20-dione-21-acetate can in turn be prepared according to example 25 of the laid-open specification 1,418,318.
Die erfindungsgemäßen 16/S-Methylsteroide, insbesondere das Acetat, besitzen eine sehr hohe entzündungshemmende Wirksamkeit, die beträchtlich größer ist als diejenige der Stammsteroide. Besonders wirksam sind sie zur Behandlung von Arthritis und damit verwandten Krankheiten, da sie zur Ausübung ihrer cortisonartigen Wirkung in äußerst geringen Dosierungen verabfolgt werden können, wodurch unerwünschte Nebenwirkungen auf ein Mindestmaß beschränkt werden. Ihre Aktivität ist besonders der 16,5-Methylgruppe zuzuschreiben, da alle bisherigen Abwandlungen, die an Steroiden der Nebennierenrinde durch Gruppensubstitution vorgenommen werden und zu einer Erhöhung der entzündungshemmenden Wirksamkeit führten, auf der Einführung von a-Substituenten beruhten.The 16 / S-methyl steroids according to the invention, in particular the acetate, possess a very high anti-inflammatory effectiveness that is considerable is larger than that of the parent steroids. They are particularly effective for treating arthritis as well related diseases as they exert their cortisone-like effects in extremely low levels Dosages can be administered, thereby minimizing undesirable side effects be restricted. Its activity is particularly attributable to the 16,5-methyl group, as all previous ones Modifications made to adrenal cortical steroids by group substitution and led to an increase in anti-inflammatory effectiveness, on the introduction of a-substituents were based.
VersuchsberichtTest report
Die erfindungsgemäßen Verbindungen Betamethason (16/?-Methyl-9a-fluor-ll/3,17a,21-trihydroxy-1,4-pregnadien-3,20-dion) und Betamethasonacetat wurden hinsichtlich ihrer entzündungshemmenden Wirkung mit den bekannten entzündungshemmenden Mitteln Prednisolon und Hydrocortison verglichen. Die sehr erhebliche Überlegenheit der erfindungsgemäßen Verbindungen geht aus der untenstehenden Tabelle hervor.The compounds according to the invention betamethasone (16 /? - methyl-9a-fluoro-II / 3.17a, 21-trihydroxy-1,4-pregnadiene-3,20-dione) and betamethasone acetate were compared with the well-known anti-inflammatory agents for their anti-inflammatory effects Means prednisolone and hydrocortisone compared. The very considerable superiority of the invention Connections are shown in the table below.
Gewogenen männlichen Ratten, deren Durchschnittsgewicht etwa 116 g betrug, wurden abgewogene Wattekügelchen implantiert. Die Steroide wurden oral in der Kost 7 Tage lang verabreicht. Am 8. Tage erfolgte die Autopsie. Die Wattekügelchen wurden zusammen mit dem sie umgebenden Granulomgewebe entfernt und gewogen. Die Versuche wurden gleichzeitig mit Ratten durchgeführt, die kein Steroid oder Hydrocortison in Standarddosierungen oder die Testverbindungen erhielten.Weighed male rats, the mean weight of which was approximately 116 g, were implanted with weighed cotton balls. The steroids were administered orally in the diet for 7 days. The autopsy took place on the 8th day. The cotton balls along with the surrounding granuloma tissue were removed and weighed. The experiments were carried out concurrently with rats not receiving any steroid or hydrocortisone at standard doses or the test compounds.
Die prozentuale Hemmung der Granulombildung für jede Dosierung der Testverbindung und des Hydrocortisons wurde aus dem Unterschied im Granulomgewicht bei Ratten, denen einerseits ein Steroid verabreicht wurde und die andererseits kein Steroid erhielten, errechnet. Aus einer graphischen Darstellung der Ergebnisse wurde diejenige Dosierung der Testverbindung bestimmt, die zur Erzielung desselben Ergebnisses wie bei Hydrocortison erforderlich war. Die Wirksamkeit der Testverbindung wird als Hydrocortisongewicht, geteilt durch das Gewicht der Testverbindung, das erforderlich ist, um einen gegebenen Hemmungsgrad (im 20- bis 50%-Bereich) hervorzurufen, ausgedrückt.The percent inhibition of granuloma formation for each dose of test compound and des Hydrocortisone was determined from the difference in granuloma weight in rats given the one hand Steroid was administered and who, on the other hand, received no steroid, is calculated. From a graphic Representation of the results that dosage of the test compound was determined to achieve the same result as was required for hydrocortisone. The effectiveness of the test compound is called the hydrocortisone weight divided by the weight of the test compound that is required to to produce a given degree of inhibition (in the 20 to 50% range).
(mg/kg)Food
(mg / kg)
gewicht
(mg)Granuloma
Weight
(mg)
bezogen auf
Hydro
cortisonEffectiveness,
related to
Hydro
cortisone
B e i s ρ i e 1 1B e i s ρ i e 1 1
Herstellung von 16/?-Methyl-9a-fluor-11 ß, 17a,21 -trihydroxy-1,4-pregnadien-Production of 16 /? - methyl-9a-fluoro-11 ß, 17a, 21 -trihydroxy-1,4-pregnadiene-
3,20-dion-21-acetat3,20-dione-21-acetate
Eine Lösung von 713 mg 16/ö-Methyl-9a-fluorll/3,17a,21-trihydroxypregnan-3,20-dion-21-acetat in 20 ml Chloroform und 2,25 ml Essigsäure wurde unter Rühren bei —20° C tropfenweise mit der Hälfte einer Lösung von 540 mg Brom in 2 ml Chloroform und 3 ml Essigsäure versetzt. Das Gemisch wurde auf 0°C erwärmt, worauf der Rest der Bromlösung zugegeben wurde. Hierauf wurde eine Lösung von 0,4 g Natriumacetat in 2 ml Wasser und dann 20 mg Natriumsulfit zugesetzt. Das Gemisch wurde im Vakuum eingeengt, um das Chloroform abzutreiben, und dann mit 20 ecm Wasser versetzt. Der Niederschlag von 2,4-Dibrom -16/9 - methyl - 9a - fluor -1 Iß, 17a,21 - trihydroxypregnan-3,20-dion-21 -acetat wurde abfiltriert, mit Wasser gewaschen und an der Luft getrocknet.A solution of 713 mg of 16 / ö-methyl-9a-fluoro III / 3.17a, 21-trihydroxypregnan-3,20-dione-21-acetate in 20 ml of chloroform and 2.25 ml of acetic acid was stirred at -20.degree Half of a solution of 540 mg of bromine in 2 ml of chloroform and 3 ml of acetic acid are added dropwise. The mixture was warmed to 0 ° C and the remainder of the bromine solution was added. A solution of 0.4 g of sodium acetate in 2 ml of water and then 20 mg of sodium sulfite were then added. The mixture was concentrated in vacuo to drive off the chloroform and then 20 ml of water were added. The precipitate of 2,4-dibromo -16/9 - methyl - 9a - fluorine -1 Iß, 17a, 21 - trihydroxypregnan-3,20-dione-21-acetate was filtered off, washed with water and air-dried.
Eine Lösung von 927 mg 2,4-Dibrom-16/9-methyl-9a - fluor -11 ,S, 17a,21 - trihydroxy - pregnan - 3,20 - dion-21-acetat in 5 ml Dimethylformamid wurde unter Stickstoff mit 200 mg Natriumbromid versetzt. Nach einer Stunde bei 25° C wurde 1 ml Dimethylanilin zugesetzt und das Gemisch weitere 21J2 Stunden auf 135° C gehalten. Dann wurde das Gemisch abgekühlt, tropfenweise zu verdünnter Salzsäure zugesetzt und das feste Rohprodukt abfiltriert, mit verdünnter Salzsäure und Wasser gewaschen und an der Luft ge- ίο trocknet. Durch Behandeln mit Adsorptionskohle und Umkristallisieren aus Aceton wurde 16^-Methyl-9a - fluor - 11/9,17a,21 - trihydroxy - 1,4 - pregnadien-3,20-dion-21-acetat erhalten. F. = 205 bis 208° C.A solution of 927 mg of 2,4-dibromo-16/9-methyl-9a-fluoro-11, S, 17a, 21-trihydroxy-pregnane-3.20-dione-21-acetate in 5 ml of dimethylformamide was mixed under nitrogen with 200 mg sodium bromide are added. After one hour at 25 ° C 1 ml of dimethylaniline was added and the mixture was further 2 1 J 2 hours at 135 ° C. The mixture was then cooled, added dropwise to dilute hydrochloric acid and the solid crude product was filtered off, washed with dilute hydrochloric acid and water and dried in the air. Treatment with adsorption charcoal and recrystallization from acetone gave 16 ^ -methyl-9a-fluoro-11 / 9,17a, 21-trihydroxy-1,4-pregnadiene-3,20-dione-21-acetate. F. = 205 to 208 ° C.
15 Beispiel 2 15 Example 2
Herstellung von 16/J-Methyl-9a-fluor-11 ß, 1 Ta,
21-trihydroxy-l,4-pregnadien-3,20-dionProduction of 16 / J-methyl-9a-fluoro-11 ß, 1 Ta,
21-trihydroxy-1,4-pregnadiene-3,20-dione
Diese Verbindung wurde durch Behandeln einer Lösung von 1,05 g 16/S-Methyl-9a-fluor-l 1/3,17<z,21 -trihydroxy- l,4-pregnadien-3,20-dion in 30 ml Methanol mit einer Lösung von 1 g Kaliumbicarbonat in 10 ml Wasser unter Stickstoff bei Rückflußtemperatur im Verlauf von 7 Minuten erhalten. Das Gemisch wurde gekühlt und mit 1 ml Essigsäure in 10 ml Wasser neutralisiert. Dann wurde das Methanol im Vakuum abgedampft und das Produkt in Äthylacetat extrahiert. Nach Entfernung des Äthylacetats wurde das gewünschte 16/5 - Methyl - 9a - fluor - Uß,17a,2l - trihydroxy - 1,4 - pregnadien - 3,20 - dion in Form von Kristallen erhalten. F. = 231 bis 234° C.This compound was prepared by treating a solution of 1.05 g of 16 / S-methyl-9a-fluoro-l 1 / 3.17 <z, 21-trihydroxy-1,4-pregnadiene-3,20-dione in 30 ml of methanol obtained with a solution of 1 g of potassium bicarbonate in 10 ml of water under nitrogen at reflux temperature over the course of 7 minutes. The mixture was cooled and neutralized with 1 ml of acetic acid in 10 ml of water. The methanol was then evaporated in vacuo and the product extracted into ethyl acetate. After removal of the ethyl acetate, the desired 16/5 - methyl - 9a - fluoro - Uß, 17a, 2l - trihydroxy - 1,4 - pregnadiene - 3,20 - dione was obtained in the form of crystals. F. = 231 to 234 ° C.
Claims (2)
Family
ID=
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