CH494218A - 3-Oximino-androstenes and gonenes - Google Patents
3-Oximino-androstenes and gonenesInfo
- Publication number
- CH494218A CH494218A CH1542266A CH1542266A CH494218A CH 494218 A CH494218 A CH 494218A CH 1542266 A CH1542266 A CH 1542266A CH 1542266 A CH1542266 A CH 1542266A CH 494218 A CH494218 A CH 494218A
- Authority
- CH
- Switzerland
- Prior art keywords
- formula
- ethynyl
- radical
- compounds
- ethyl
- Prior art date
Links
- KZFUFKLPCCYROA-VMXHOPILSA-N N-[(8S,9S,10R,13S,14S)-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-ylidene]hydroxylamine Chemical class N(O)=C1C=C2CC[C@@H]3[C@H](CC[C@@]4(CCC[C@H]43)C)[C@]2(CC1)C KZFUFKLPCCYROA-VMXHOPILSA-N 0.000 title abstract 2
- 150000003805 gonenes Chemical class 0.000 title 1
- 238000000034 method Methods 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 150000002923 oximes Chemical class 0.000 claims description 8
- XEHVFKKSDRMODV-UHFFFAOYSA-N ethynyl Chemical compound C#[C] XEHVFKKSDRMODV-UHFFFAOYSA-N 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 150000003254 radicals Chemical class 0.000 claims description 4
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 2
- 238000005984 hydrogenation reaction Methods 0.000 claims description 2
- 150000002443 hydroxylamines Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 8
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000007787 solid Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- 239000012445 acidic reagent Substances 0.000 description 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- GRDXCFKBQWDAJH-UHFFFAOYSA-N 4-acetamidobenzenesulfonyl chloride Chemical compound CC(=O)NC1=CC=C(S(Cl)(=O)=O)C=C1 GRDXCFKBQWDAJH-UHFFFAOYSA-N 0.000 description 1
- MTOJDBAZGOYUOZ-UHFFFAOYSA-N 4-aminobenzenesulfonyl chloride Chemical compound NC1=CC=C(S(Cl)(=O)=O)C=C1 MTOJDBAZGOYUOZ-UHFFFAOYSA-N 0.000 description 1
- 238000006237 Beckmann rearrangement reaction Methods 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- RPOYGOULCHMVBB-ADDDGJNWSA-N Pipercide Chemical compound CC(C)CNC(=O)\C=C\C=C\CCCC\C=C\C1=CC=C2OCOC2=C1 RPOYGOULCHMVBB-ADDDGJNWSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- SCTDPGXGNWEFNF-ZCPXKWAGSA-N [(8R,9S,10R,13S,14S,17R)-17-ethynyl-3-hydroxyimino-13-methyl-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1CC2=CC(=NO)CC[C@@H]2[C@@H]2[C@@H]1[C@@H]1CC[C@](C#C)(OC(=O)C)[C@@]1(C)CC2 SCTDPGXGNWEFNF-ZCPXKWAGSA-N 0.000 description 1
- NXQOQNROJJFYCJ-FZFXZXLVSA-N androst-16-ene Chemical compound C1CCC[C@]2(C)[C@H]3CC[C@](C)(C=CC4)[C@@H]4[C@@H]3CCC21 NXQOQNROJJFYCJ-FZFXZXLVSA-N 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 230000002254 contraceptive effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 230000035558 fertility Effects 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/567—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in position 17 alpha, e.g. mestranol, norethandrolone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
- A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
- A61K31/569—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone substituted in position 17 alpha, e.g. ethisterone
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Steroid Compounds (AREA)
Abstract
3-Oximino-androstenes and -gonenes of the formula:- (I) R = H or Me R' = Me or Et Broken bond optional Pharmaceuticals.
Description
Verfabren zur Herstellung von 3-Hydroxyimino-steroiden
Die Erfindung betrifft ein Verfahren zur Herstellung von neuen 3-Oximen insbesondere der Androsten- und Gonanreihe, nämlich von Oximen der Formel II
EMI1.1
oder von 6,7-Dehydroderivaten davon, in welcher Formel R Wasserstoff oder den Methylrest, R' den Methyloder Äthylrest und R" den Äthyl-, Vinyl- oder Äthinylrest bedeutet, das dadurch gekennzeichnet ist, dass man die entsprechenden 3-Carbonylverbindungen mit Hydroxylamin oder einem Hydroxylaminsalz in Gegenwart einer Base umsetzt.
Beispielsweise können nach dem erfindungsgemässen Verfahren Verbindungen der Formel I bzw. III hergestellt werden.
EMI1.2
EMI1.3
Die Verbindungen der Formel II besitzen hormonale
Aktivität und können beispielsweise wertvolle pharma kologische Wirksamkeit als empfängnis- und geburtenverhindernde Mittel aufweisen.
Die Erfindung betrifft femer die Verwendung der nach dem erfindungsgemässen Verfahren hergestellten Oxime der Formel II, in welcher R" der Äthinylrest ist, zur Herstellung von Hydrierungsprodukten, wobei diese Verwendung dadurch gekennzeichnet ist, dass die 17 -Äthinylgruppe zur 17-Äthenyl- oder 17-Äthylgruppe hydriert wird.
Als spezielle Beispiele für Ausgangsmaterialien zur Durchführung des erfindungsgemässen Verfahrens seien die Verbindungen der Formel
EMI1.4
EMI2.1
genannt, worin R Wasserstoff oder Methyl und R' Methyl oder Äthyl ist.
Bei der erfindungsgemässen Umsetzung kann als Base z.B. Pyridin, Natriumhydroxyd oder Natriumacetat verwendet werden. Die erhaltenen 3-Oxime der Formel II können einer Beckmann-Umlagerung in Gegenwart eines sauren Reagens unterworfen werden, wobei die entsprechenden 3-Aza-A-homosteroide gebildet werden.
Typische saure Reagentien, die verwendet werden können, sind Thionylchlorid, Polyphosphorsäure, p-Toluolsulfonylchlorid, p-Acetylaminobenzolsulfonylchlorid, p -Aminobenzolsulfonylchlorid und Phosphorpentachlorid.
Vorzugsweise werden nach dem erfindungsgemässen Verfahren solche Verbindungen der Formel I hergestellt, in denen entweder beide Reste R und R' Methylgruppen sind, oder der Rest R' die Äthylgruppe ist, während der Rest R entweder die Methylgruppe oder ein Wasserstoffatom ist. In diesen vorzugsweise hergestellten Verbindungen der Formel II kann in der Stellung 6-7 entweder eine Einfachbindung oder eine Doppelbindung vorliegen. Für den Fall, dass die nach dem erfindungsgemässen Verfahren hergestellten Verbindungen in der Stellung 6-7 eine Doppelbindung aufweisen, besitzen die Verbindungen auch dann sehr gute pharmakologische Eigenschaften, wenn R ein Wasserstoffatom ist und R' eine CH3-Gruppe bedeutet.
Beispiel 1
Eine Lösung von 2,0 g 17α-Äthinyl-17ss-acetoxy-4-an- drosten-3-on, 10 ml Pyridin und 1,0 g Hydroxylaminhydrochlorid wird eine halbe Stunde auf dem Dampfbad erhitzt. Das Gemisch wird in 300 ml Eiswasser gegossen und der hierbei ausgefällte Feststoff abfiltriert. Durch Umkristallisation aus Methanol-Wasser werden 1,95 g (94%) 17ol-Äthinyl-17B -acetoxy-4-androsten-3 -on-oxim vom Schmelzpunkt 183 - 1850C erhalten. ) maX 238 m .
Analyse für C23H31NO3:
Ber.: C 74,76 H 8,46 N 3,79
Gef.: C 74,63 H 8,62 N 3,51
Beispiel 2
Eine Lösung von 2,0g 17x-Äthinyl-170-acetoxy-19- -norandrost-4-en-3-on, 10 ml Pyridin und 1,0 g Hydroxylaminhydrochlorid wird auf dem Dampfbad eine halbe Stunde erhitzt. Das Gemisch wird in eine grosse Menge Eis und Wasser gegossen und der hierbei abgeschiedene Feststoff abfiltriert. Er wird aus Methanol-Wasser umkristallisiert, wobei 1,6 g (78%) 17x-Äthinyl-17,ss-acetoxy- -l9-norandrost-4-en-3-on-oxim vom Schmelzpunkt 2292300 erhalten werden. man 238 m.
Analyse für C22H29NO3:
Ber.: C 74,33 H 8,22 N 3,94
Gef.: C 74,39 H 8,21 N 4,01
Beispiel 3
Eine Lösung, die 4,0g 17a-Athinyl-l7})-acetoxy-l9- -norandrost-4,6-dien-3-on, 2,0 g Hydroxylaminhydrochlo rid und 25 ml Pyridin enthält, wird auf dem Dampfbad 0,5 Stunden erhitzt. Sie wird auf eine grosse Menge Eis und Wasser gegossen. Der hierbei gebildete Feststoff wird abfiltriert. Durch Umkristallisation aus Methanol Wasser werden 3,9 g (94%) 17x-Athinyl-17k-acetoxy-19- -norandrost-4,6-dien-3-on-oxim vom Schmelzpunkt 254 bis 2560 erhalten. #max 278 mull.
Analyse für C32H2TNO3:
Ber.: C 74,75 H 7,70 N 3,96
Gef.: C 75,17 H 7,96 N 3,82
Beispiel 4
Auf die in Beispiel 3 beschriebene Weise, jedoch bei Verwendung von 17α-Äthinyl-17ss-acetoxy-androst-4,6- -dien-3-on als Ausgangsmaterial wird 17Sa-Athinyl-170- -acetoxy-androst-4,6-dien-3-on-oxim vom Schmelzpunkt
228 - 2300 in 78%iger Ausbeute hergestellt. )wmaX 278 mp.
Analyse für C2sH29NO3
Ber.: C 75,17 H 7,95 N 3,81
Gef.: C 74,93 H 8,20 N 3,68
Beispiel 5
Eine Lösung, die 4,5 g DL-13ss-Äthyl-17α-äthinyl-17ss- -acetoxy-gon-4-en-3-on in 15 mol Pyridin und 2,0g Hydroxylaminhydrochlorid enthält, wird 45 Minuten auf dem
Dampfbad erhitzt. Sie wird abgekühlt und in eine grosse Menge Eis und Wasser gegossen. Der hierbei gebildete
Feststoff wird abfiltriert und an der Luft getrocknet. Er wird aus einem Methylenchlorid-Alkohol-Gemisch umkristallisiert, wobei 4,2 g DL-13p-Athyl-l7la-äthinyl-l743 -acetoxy-gon-4-en-3-on-oxim vom Schmelzpunkt 226-2280 erhalten werden.
Analyse für C23H3,NO3:
Ber.: C 74,76 H 8,46 N 3,79
Gef.: C 74,84 H 8,75 N 3,90
Gemäss den vorstehenden Beispielen wurde auch die folgende Verbindung hergestellt.
DL- 13X,-Äthyl- 17a-äthinyl- 170-acetoxy-gon-4,6-dien-3- -on-oxim.
In der folgenden Tabelle werden Werte bei der Klas sierung nach endokrinologischen Vergleichsversuchen an geführt, wobei, falls nicht anders angegeben ist, die entsprechenden Präparate oral verabreicht wurden und die in der Tabelle angeführten Eigenschaften zeigt.
EMI2.2
Noräthindron-acetat-oxim; 170-Acetoxy-17,a-äthinyl-4- -östren-3-on-3 -oxim; 17ss-Acetoxy-17α-äthinyl-19-nor-4- -androsten-3-on-oxim.
Aktivität ausgedrückt in Wert Progestional Bereich der Gesamtmilligramm, die zur Erzeugung von 1,0
McPhail-Indices im Bereich von 1-3 bei unreifen Kanin chen nötig sind.
Geburtenverhindernd MED, in mg/kg, die zur wesentlichen Herabsetzung der 0,5
Fruchtbarkeit bei Ratten benötigt werden. 0,25 Östrogen Gesamtmilligramm, um eine l00SOige Gewichtszunahme 100 ffi g des Uterus bei einer unreifen Ratte hervorzurufen. 6,4 ffi g s.c.
Claudogen Ratte 0,25-0,5 mg/kg
Process for the production of 3-hydroxyimino-steroids
The invention relates to a process for the preparation of new 3-oximes, in particular of the androstene and gonan series, namely oximes of the formula II
EMI1.1
or of 6,7-dehydroderivatives thereof, in which formula R denotes hydrogen or the methyl radical, R 'denotes the methyl or ethyl radical and R "denotes the ethyl, vinyl or ethynyl radical, which is characterized in that the corresponding 3-carbonyl compounds are mixed with hydroxylamine or a hydroxylamine salt in the presence of a base.
For example, compounds of the formula I or III can be prepared by the process according to the invention.
EMI1.2
EMI1.3
The compounds of formula II are hormonal
Activity and can, for example, have valuable pharmacological effectiveness as a contraceptive and birth prevention agent.
The invention further relates to the use of the oximes of the formula II prepared by the process according to the invention, in which R "is the ethynyl radical, for the preparation of hydrogenation products, this use being characterized in that the 17-ethynyl group to the 17-ethynyl or 17- Ethyl group is hydrogenated.
Specific examples of starting materials for carrying out the process according to the invention are the compounds of the formula
EMI1.4
EMI2.1
called, wherein R is hydrogen or methyl and R 'is methyl or ethyl.
In the reaction according to the invention, e.g. Pyridine, sodium hydroxide or sodium acetate can be used. The 3-oximes of the formula II obtained can be subjected to a Beckmann rearrangement in the presence of an acidic reagent, the corresponding 3-aza-A-homosteroids being formed.
Typical acidic reagents that can be used are thionyl chloride, polyphosphoric acid, p-toluenesulfonyl chloride, p-acetylaminobenzenesulfonyl chloride, p -aminobenzenesulfonyl chloride, and phosphorus pentachloride.
Compounds of the formula I in which either both radicals R and R 'are methyl groups or the radical R' is the ethyl group while the radical R is either the methyl group or a hydrogen atom are preferably prepared by the process according to the invention. In these compounds of the formula II, which are preferably prepared, either a single bond or a double bond can be present in the 6-7 position. In the event that the compounds prepared by the process according to the invention have a double bond in the 6-7 position, the compounds also have very good pharmacological properties when R is a hydrogen atom and R 'is a CH3 group.
example 1
A solution of 2.0 g of 17α-ethynyl-17ss-acetoxy-4-anrosten-3-one, 10 ml of pyridine and 1.0 g of hydroxylamine hydrochloride is heated on the steam bath for half an hour. The mixture is poured into 300 ml of ice water and the solid which has precipitated out is filtered off. Recrystallization from methanol-water gives 1.95 g (94%) 17ol-ethynyl-17B-acetoxy-4-androsten-3-one oxime with a melting point of 183-1850C. ) max 238 m.
Analysis for C23H31NO3:
Calc .: C 74.76 H 8.46 N 3.79
Found: C 74.63 H 8.62 N 3.51
Example 2
A solution of 2.0 g of 17x-ethynyl-170-acetoxy-19- norandrost-4-en-3-one, 10 ml of pyridine and 1.0 g of hydroxylamine hydrochloride is heated on the steam bath for half an hour. The mixture is poured into a large amount of ice and water and the solid that has separated out is filtered off. It is recrystallized from methanol-water, 1.6 g (78%) of 17x-ethynyl-17, ss-acetoxy-19-norandrost-4-en-3-one oxime with a melting point of 2292300 being obtained. one 238 m.
Analysis for C22H29NO3:
Calc .: C 74.33 H 8.22 N 3.94
Found: C 74.39 H 8.21 N 4.01
Example 3
A solution containing 4.0 g of 17a-ethynyl-l7}) - acetoxy-l9- -norandrost-4,6-dien-3-one, 2.0 g of hydroxylamine hydrochloride and 25 ml of pyridine is placed on the steam bath 0, Heated for 5 hours. It is poured onto a large amount of ice and water. The solid formed in this way is filtered off. Recrystallization from methanol / water gives 3.9 g (94%) of 17x-ethynyl-17k-acetoxy-19- norandrost-4,6-dien-3-one oxime with a melting point of 254 to 2560. #max 278 mull.
Analysis for C32H2TNO3:
Calcd .: C 74.75 H 7.70 N 3.96
Found: C 75.17 H 7.96 N 3.82
Example 4
In the manner described in Example 3, but using 17α-ethynyl-17ss-acetoxy-androst-4,6- -dien-3-one as starting material, 17Sa-ethynyl-170- acetoxy-androst-4,6 is obtained -dien-3-one oxime of the melting point
228-2300 produced in 78% yield. ) wmaX 278 mp.
Analysis for C2sH29NO3
Calculated: C 75.17 H 7.95 N 3.81
Found: C 74.93 H 8.20 N 3.68
Example 5
A solution containing 4.5 g of DL-13ss-ethyl-17α-ethinyl-17ss-acetoxy-gon-4-en-3-one in 15 mol of pyridine and 2.0 g of hydroxylamine hydrochloride is left on the
Steam bath heated. It is cooled and poured into a large amount of ice and water. The here formed
The solid is filtered off and air-dried. It is recrystallized from a methylene chloride-alcohol mixture, 4.2 g of DL-13p-ethyl-17la-ethinyl-1743-acetoxy-gon-4-en-3-one oxime with a melting point of 226-2280 being obtained.
Analysis for C23H3, NO3:
Calc .: C 74.76 H 8.46 N 3.79
Found: C 74.84 H 8.75 N 3.90
The following compound was also prepared according to the preceding examples.
DL-13X, -Ethyl-17a-ethinyl-170-acetoxy-gon-4,6-diene-3-one-oxime.
In the following table, values for the classification according to endocrinological comparative tests are given, with the corresponding preparations being administered orally and showing the properties listed in the table, unless otherwise stated.
EMI2.2
Norethindrone acetate oxime; 170-acetoxy-17, a-ethinyl-4-oestren-3-one-3-oxime; 17ss-acetoxy-17α-ethinyl-19-nor-4-androsten-3-one oxime.
Activity expressed in value Progestional Area of the total milligrams necessary to generate 1.0
McPhail indices in the range of 1-3 are necessary for immature rabbits.
Birth preventive MED, in mg / kg, which significantly reduces the 0.5
Fertility in rats are needed. 0.25 total estrogen milligrams to produce 100% uterine weight gain in an immature rat. 6.4 ffi g s.c.
Claudogen rat 0.25-0.5 mg / kg
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50238465A | 1965-10-22 | 1965-10-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH494218A true CH494218A (en) | 1970-07-31 |
Family
ID=23997569
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1542266A CH494218A (en) | 1965-10-22 | 1966-10-24 | 3-Oximino-androstenes and gonenes |
Country Status (3)
| Country | Link |
|---|---|
| CH (1) | CH494218A (en) |
| GB (1) | GB1123104A (en) |
| SE (1) | SE325271B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005000867A1 (en) * | 2003-06-30 | 2005-01-06 | Richter Gedeon Vegyészeti Gyár Rt. | PURE D-(17α)-13-ETHYL-17-HYDROXY-18,19-DINORPREGN-4-ENE-20-YNE-3-ONE-3E- AND -3Z-OXIME ISOMERS, AS WELL AS PROCESS FOR THE SYNTHESIS OF THE MIXTURE OF ISOMERS AND THE PURE ISOMERS |
| US7576226B2 (en) | 2003-06-30 | 2009-08-18 | Richter Gedeon Vegyeszeti Gyar Rt. | Process of making isomers of norelgestromin and methods using the same |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU3257993A (en) * | 1991-12-22 | 1993-07-28 | Schering Aktiengesellschaft | 3-methylsulphonylhydrazono and 3-oxyimino steroids, a method of preparing them, pharmaceutical preparations containing them and their use in the preparation of drugs |
| TW200621796A (en) * | 2004-08-12 | 2006-07-01 | Sicor Inc | Process for the preparation of 3-oximino steroids |
-
1966
- 1966-09-02 GB GB3928066A patent/GB1123104A/en not_active Expired
- 1966-10-21 SE SE1442866A patent/SE325271B/xx unknown
- 1966-10-24 CH CH1542266A patent/CH494218A/en not_active IP Right Cessation
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005000867A1 (en) * | 2003-06-30 | 2005-01-06 | Richter Gedeon Vegyészeti Gyár Rt. | PURE D-(17α)-13-ETHYL-17-HYDROXY-18,19-DINORPREGN-4-ENE-20-YNE-3-ONE-3E- AND -3Z-OXIME ISOMERS, AS WELL AS PROCESS FOR THE SYNTHESIS OF THE MIXTURE OF ISOMERS AND THE PURE ISOMERS |
| EA008174B1 (en) * | 2003-06-30 | 2007-04-27 | Рихтер Гедеон Ведьесети Дьяр Рт. | PURE D-(17α)-13-ETHYL-17-HYDROXY-18,19-DINORPREGN-4-ENE-20-YNE-3-ONE-3E- AND -3Z-OXIME ISOMERS, AS WELL AS PROCESS FOR THE SYNTHESIS OF THE MIXTURE OF ISOMERS AND THE PURE ISOMERS |
| US7576226B2 (en) | 2003-06-30 | 2009-08-18 | Richter Gedeon Vegyeszeti Gyar Rt. | Process of making isomers of norelgestromin and methods using the same |
| US7816546B2 (en) | 2003-06-30 | 2010-10-19 | Richter Gedeon Vegyeszeti Gyar Rt. | Process for the synthesis of high purity d-(17α)-13-ethyl-17-hydroxy-18,19-dinorpregn-4-ene-20-yn-3-one-oxime |
Also Published As
| Publication number | Publication date |
|---|---|
| SE325271B (en) | 1970-06-29 |
| GB1123104A (en) | 1968-08-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CH494218A (en) | 3-Oximino-androstenes and gonenes | |
| DE2107356C3 (en) | Thieno [23-e] - [1,4] diazepin-2-ones, process for their preparation and pharmaceuticals containing them | |
| DE2013032C3 (en) | 3-Amino-cardenolide, process for their preparation and their use in combating cardiovascular diseases | |
| DE1111208B (en) | Process for the production of cough-relieving, basic substituted diphenylcarbinol esters | |
| DE2335827A1 (en) | 2BETA-HYDROXY-3ALPHA-AMINOSTEROIDS, THEIR DERIVATIVES AND THE PROCESS FOR THEIR PRODUCTION | |
| DE1223377B (en) | Process for the preparation of 3,5-Dioxo-17alpha-ethyl-17beta-hydroxy-A-nor-B-homo-oestrane | |
| CH520117A (en) | 5h-dibenzo-a d-10 11-dihydro-cyclohepten-5-one oximes | |
| CH526526A (en) | 6-alpha methyl-17 alpha-caproyloxy-19-non- - progesterone having progestative and anti- | |
| DE2217965C3 (en) | 2alpha-methyl-17 beta-cyclopentyloxy -5 alpha-androstan-3-one, process for its preparation and agent containing it | |
| DE2331044A1 (en) | DIPHENYLMETHANE DERIVATIVES AND PROCESS FOR THEIR PRODUCTION | |
| AT210886B (en) | Process for the preparation of new, basic substituted diphenylcarbinol esters and their salts | |
| DE2056512C3 (en) | ||
| DE1620102C3 (en) | 3-Oximes of the androstene and gonen series, process for their preparation and pharmaceutical compositions containing them | |
| AT306724B (en) | Process for the preparation of new 1,4-benzodiazepines and their salts | |
| DE1183501B (en) | Process for the production of 18-dichloro steroids | |
| AT253689B (en) | Process for the production of new, basic substituted steroid compounds | |
| AT261820B (en) | Process for the production of new steroid guanylhydrazones | |
| AT251770B (en) | Process for the production of new, basic substituted, therapeutically active steroid compounds | |
| AT253704B (en) | Process for the preparation of the new 7α-methyl-16α-hydroxy-estrone and its 3,16-diacetate | |
| AT203155B (en) | Process for the manufacture of basic steroids | |
| AT221087B (en) | Process for the production of new, basic indole derivatives | |
| DE1618028A1 (en) | Process for the preparation of methylacyloxymethyl ketals from prednisolone derivatives with 3 to 5 carbon atoms in the acyl group | |
| DE1007776B (en) | Process for the preparation of N-substituted 16-amino steroids | |
| DE1179548B (en) | Process for the preparation of 21-bromo steroids | |
| DE1620102B2 (en) | 3-Oximes of the androstene and gonen series, process for their preparation and pharmaceutical compositions containing them |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |