CH545776A - 21-Aldehydes of the pregnane series - anti-inflammatory, thymolytic, anti-leukaemia intermediates - Google Patents
21-Aldehydes of the pregnane series - anti-inflammatory, thymolytic, anti-leukaemia intermediatesInfo
- Publication number
- CH545776A CH545776A CH851671A CH851671A CH545776A CH 545776 A CH545776 A CH 545776A CH 851671 A CH851671 A CH 851671A CH 851671 A CH851671 A CH 851671A CH 545776 A CH545776 A CH 545776A
- Authority
- CH
- Switzerland
- Prior art keywords
- alcohols
- methyl
- aldehydes
- dependent
- dihydroxy
- Prior art date
Links
- 150000003128 pregnanes Chemical class 0.000 title claims description 3
- 230000003110 anti-inflammatory effect Effects 0.000 title abstract description 4
- 230000003096 thymolvtic effect Effects 0.000 title abstract description 3
- 239000000543 intermediate Substances 0.000 title description 2
- 208000032839 leukemia Diseases 0.000 title 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 16
- 150000001298 alcohols Chemical class 0.000 claims description 15
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 150000002373 hemiacetals Chemical class 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 230000002378 acidificating effect Effects 0.000 claims description 6
- 230000001419 dependent effect Effects 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 5
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 4
- 150000004677 hydrates Chemical class 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- RLAHWVDQYNDAGG-UHFFFAOYSA-N Methanetriol Chemical class OC(O)O RLAHWVDQYNDAGG-UHFFFAOYSA-N 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- 229960000583 acetic acid Drugs 0.000 claims description 2
- 238000007865 diluting Methods 0.000 claims description 2
- 239000012362 glacial acetic acid Substances 0.000 claims description 2
- 239000002244 precipitate Substances 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 3
- 239000002253 acid Substances 0.000 abstract description 2
- 239000002260 anti-inflammatory agent Substances 0.000 abstract description 2
- 230000000719 anti-leukaemic effect Effects 0.000 abstract description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract 1
- 125000004185 ester group Chemical group 0.000 abstract 1
- 125000001033 ether group Chemical group 0.000 abstract 1
- 235000019441 ethanol Nutrition 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 11
- -1 aldehyde acetals Chemical class 0.000 description 7
- 239000000243 solution Substances 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- UJOAKMDKXSGYEN-QHKWGSLXSA-N (8R,9S,10S,13S)-1-methoxy-17-(2-methoxyacetyl)-10,13-dimethyl-1,2,4,5,6,7,8,9,11,12-decahydrocyclopenta[a]phenanthren-3-one Chemical compound COC1CC(CC2CC[C@H]3C4=CC=C(C(COC)=O)[C@]4(CC[C@@H]3[C@@]12C)C)=O UJOAKMDKXSGYEN-QHKWGSLXSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 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 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical class CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 239000000063 antileukemic agent Substances 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 150000003938 benzyl alcohols Chemical class 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- WERYXYBDKMZEQL-UHFFFAOYSA-N butane-1,4-diol Chemical class OCCCCO WERYXYBDKMZEQL-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Compds. of the general formula (I) R1 and R2 = OH, an ester residue (pref. of a 1-18C acid) or an ether residue (pref. of a 1-8C alcohol), or R1 + R2 = 0. Anti-inflammatories, thymolytics, and anti-leukemics.
Description
Gegenstand der vorliegenden Erfindung ist ein Verfahren zur Herstellung von Aldehydacetalen von 21-Aldehyden der Pregnanreihe der Formel
EMI1.1
worin R1 und R2 Hydroxygruppen bedeuten, von denen mindestens eine veräthert ist.
Als verätherte Hydroxygruppen sind besonders diejenigen zu nennen, welche sich von Alkoholen mit 14 Kohlenstoffatomen ableiten, wie niederaliphatischen Alkanolen, Äthylalkohol, Methylalkohol, Propylalkohol, iso-Propylalkohol, den Butyl- oder Amylalkoholen oder von araliphatischen Alkoholen, insbesondere von monocyclischen arylniederaliphatischen Alkoholen, wie Benzylalkohol, oder von heterocyclischen Alkoholen, wie a-Tetrahydropyranol oder -furanol.
Besonders zu erwähnen sind auch cyclische Äther, die sich von mehrwertigen Alkoholen ableiten, z. B. von Äthylen- glykol, den Propylenglykolen oder Butylenglykolen.
Die neuen Verbindungen der obigen Formel (I) besitzen wertvolle pharmakologische Eigenschaften. So weisen sie insbesondere eine antiinflammatorische und thymolytische Wirkung auf, wie sich im Tierversuch, z. B. an der Ratte, zeigt.
Ferner besitzen sie, z. B. im Tierversuch, wie beispielsweise an der Ratte (Fischer-Ratten RS) eine antileukämische Wirkung. Die neuen Verbindungen können daher als antiinflammatorische und antileukämische Mittel Verwendung finden. Die neuen Verbindungen sind aber auch wertvolle Zwischenprodukte für die Herstellung anderer nützlicher Stoffe, insbesondere von pharmakologisch wirksamen Verbindungen.
Das Verfahren der vorliegenden Erfindung ist dadurch gekennzeichnet, dass man 21-Aldehyde oder ihre Hydrate oder Hemiacetale der Formel
EMI1.2
worin R3 und R4 je eine freie Hydroxygruppe darstellen, von denen höchstens eine veräthert sein kann, oder R3 zusammen mit R4 eine Oxogruppe bedeuten, mit veräthernden Mitteln behandelt.
Als veräthernde Mittel verwendet man vorzugsweise Alkohole, wenn erwünscht in Gegenwart eines sauren Katalysators, wie einer Mineralsäure, z. B. Salzsäure. In Abwesenheit eines sauren Katalysators entstehen aus den freien Aldehyden oder deren Hydraten vorzugsweise die Hemiacetale, während in Anwesenheit eines sauren Katalysators die Diacetale entstehen. Man verwendet insbesondere die oben genannten Alkohole. Die entsprechende Umsetzung mit mehrwertigen Alkoholen führt zu den eingangs genannten cyclischen Acetalen. Man kann zur Acetalbildung die freien Aldehyde, deren Hemiacetale oder die entsprechenden 21,21-Dihydroxyverbindungen auch mit Orthoameisen- säureestern der betreffenden Alkohole umsetzen.
Falls erwünscht, können die genannten Acetale durch saure Verseifung in die freien Aldehyde bzw. in die entsprechenden 21,2 1-Dihydroxyverbindungen übergeführt werden.
Die neuen Verbindungen der vorliegenden Erfindung können zur Herstellung von pharmazeutischen Präparaten zur Anwendung in der Human- oder Veterinärmedizin verwendet werden. Als pharmazeutische Träger verwendet man organische oder anorganische Stoffe, die für die enterale, z. B. orale, parenterale oder topische Gabe geeignet sind. Für die Bildung derselben kommen solche Stoffe in Frage, die mit den neuen Verbindungen nicht reagieren, wie z. B. Wasser, Gelatine, Milchzucker, Stärke, Magnesiumstearat, Talk, pflanzliche Öle, Benzylalkohole, Gummi, Polyalkylenglykole, Vaseline, Cholesterin und andere bekannte Arzneimittelträger. Die pharmazeutischen Präparatekönnen in fester Form, z. B. als Tabletten, Dragees oder Kapseln, oder in flüssiger oder halbflüssiger Form als Lösungen, Suspensionen, Emulsionen, Salben oder Cremen vorliegen.
Gegebenenfalls sind diese pharmazeutischen Präparate sterilisiert und bzw. oder enthalten Hilfsstoffe, wie Konservierungs-, Stabilisierungs-, Netz- oder Emulgiermittel, Salze zur Ver änderung des osmotischen Druckes oder Puffer. Sie können auch noch andere therapeutisch wertvolle Stoffe enthalten.
Die neuen Verbindungen können auch als Ausgangsprodukte für die Herstellung anderer wertvoller Verbindungen dienen.
0,455 g des erhalteneni 1,4-6a,9a-Difluor-16a-methyl- 1 lss,17a-dihydroxy-21,21-dimethoxy-3,20-dioxo-pregnadiens löst man in 25 ml Tetrahydrofuran und setzt 75 ml 2,66molare wässrige Perchlorsäure zu. Die Lösung wird während 10 Stunden einer langsamen Destillation unter vermindertem Druck unterworfen, wobei das abdestillierende Tetrahydrofuran-Wasser-Gemisch laufend ersetzt wird. Man versetzt hierauf die Lösung mit 125 ml Wasser, engt zur Entfernung der Hauptmenge des Tetrahydrofurans im Vakuum ein,
Die genannten Verbindungen können auch als Futterzusatzmittel verwendet werden.
Die Erfindung wird in den folgenden Beispielen näher beschrieben. Die Temperaturen sind in Celsiusgraden angegeben.
Beispiel
1,065 g Hydrat des d 1,4-6u,9a-Difluor-16a-methyl- llss,17u -dihydroxy-3,20,2 1-trioxo-pregnadiens werden mit 100 ml einer 1 zeigen Lösung von Chlorwasserstoff in Methanol übergossen. Nachdem das Reaktionsgemisch 16 Stunden bei Raumtemperatur gerührt worden ist, dampft man es im Vakuum ein, nimmt das rohe Dimethylacetal in Methylenchlorid auf und filtriert die Lösung durch eine Säule von 25 g Aluminiumoxyd (Aktivität IV). Die mit Methylenchlorid-Äther (1:1) erhaltenen Eluate werden vereinigt und im Vakuum konzentriert. Auf vorsichtigen Zusatz von Äther scheidet sich dasi 1,4-6a,9a-Difluor- 16a-methyl-1 lss, 17a- dihydroxy-2 1,2 1-dimethoxy-3 ,20-dioxo-pregnadien aus.
worauf das Hydrat des zl lç4-6a,9a-Difluor-16a-methyl- 1 lss,17a-dihydroxy-3,20,21-trioxo-pregnadiens ausfällt.
0,328 g des erhaltenen Aldehyd-hydrats wird in 30 ml Methanol gelöst und die Lösung nach Zugabe von 0,03 ml Eisessig und Verdünnen mit 120 ml Wasser auf ein Restvolumen von 12,5 ml eingeengt. Man erhält auf diese Weise das d 1,4-6a,9a-Difluor- 16a-methyl- 11ss, 17a-dihydroxy- 3,20,21-trioxo-pregnadien in der Form des 21-Methyl-hemiacetals vom F. 129-135 .
PATENTANSPRUCTI
Verfahren zur Herstellung von 21-Aldehydacetalen bzw.
Hemiacetalen der Pregnanreihe der Formel
EMI2.1
worin R1 und R2 Hydroxygruppen bedeuten, von denen mindestens eine veräthert ist, dadurch gekennzeichnet, dass man 21-Aldehyde oder ihre Hydrate oder Hemiacetale der Formel
EMI2.2
worin R3 und R4 Hydroxygruppen darstellen, von denen höchstens eine veräthert sein kann, oder R3 zusammen mit R4 eine Oxogruppe bedeuten, mit veräthernden Mitteln behandelt.
UNTERANSPRÜCHE
1. Verfahren nach Patentanspruch, dadurch gekennzeichnet, dass man Alkohole als veräthernde Mittel verwendet.
2. Verfahren nach Patentanspruch, dadurch gekennzeichnet, dass man Alkohole in Anwesenheit eines sauren Katalysators verwendet.
3. Verfahren nach Patentanspruch oder einem der Unteransprüche 1-2, dadurch gekennzeichnet, dass man Alkohole mit 1-8 Kohlenstoffatomen verwendet.
4. Verfahren nach Patentanspruch oder einem der Unteransprüche 1-2, dadurch gekennzeichnet, dass man zweiwertige Alkohole verwendet.
5. Verfahren nach Patentanspruch oder einem der Unteransprüche 1-2, dadurch gekennzeichnet, dass man Methylalkohol verwendet.
6. Verfahren nach Patentanspruch, dadurch gekennzeichnet, dass man Orthoameisensäureester der betreffenden Alkohole als veräthernde Mittel verwendet.
**WARNUNG** Ende DESC Feld konnte Anfang CLMS uberlappen**.
The present invention relates to a process for the preparation of aldehyde acetals from 21-aldehydes of the pregnane series of the formula
EMI1.1
where R1 and R2 are hydroxyl groups, at least one of which is etherified.
The etherified hydroxyl groups are particularly those which are derived from alcohols with 14 carbon atoms, such as lower aliphatic alkanols, ethyl alcohol, methyl alcohol, propyl alcohol, isopropyl alcohol, butyl or amyl alcohols or from araliphatic alcohols, in particular from monocyclic aryl lower aliphatic alcohols such as benzene alcohols , or of heterocyclic alcohols such as α-tetrahydropyranol or -furanol.
Cyclic ethers derived from polyhydric alcohols, e.g. B. of ethylene glycol, propylene glycols or butylene glycols.
The new compounds of the above formula (I) have valuable pharmacological properties. In particular, they have an anti-inflammatory and thymolytic effect, as shown in animal experiments, e.g. B. on the rat shows.
They also have such. B. in animal experiments, such as in rats (Fischer rats RS) an antileukemic effect. The new compounds can therefore be used as anti-inflammatory and anti-leukemic agents. However, the new compounds are also valuable intermediates for the preparation of other useful substances, in particular pharmacologically active compounds.
The process of the present invention is characterized in that 21-aldehydes or their hydrates or hemiacetals of the formula
EMI1.2
wherein R3 and R4 each represent a free hydroxyl group, of which at most one can be etherified, or R3 together with R4 represent an oxo group, treated with etherifying agents.
The etherifying agents used are preferably alcohols, if desired in the presence of an acidic catalyst such as a mineral acid, e.g. B. hydrochloric acid. In the absence of an acidic catalyst, the hemiacetals are preferably formed from the free aldehydes or their hydrates, while the diacetals are formed in the presence of an acidic catalyst. The alcohols mentioned above are used in particular. The corresponding reaction with polyhydric alcohols leads to the cyclic acetals mentioned at the outset. For acetal formation, the free aldehydes, their hemiacetals or the corresponding 21,21-dihydroxy compounds can also be reacted with orthoformic acid esters of the alcohols concerned.
If desired, the acetals mentioned can be converted into the free aldehydes or into the corresponding 21,2 1-dihydroxy compounds by acidic saponification.
The new compounds of the present invention can be used for the manufacture of pharmaceutical preparations for use in human or veterinary medicine. The pharmaceutical carrier used is organic or inorganic substances which are suitable for enteral, e.g. B. oral, parenteral or topical administration are suitable. For the formation of the same substances come into question that do not react with the new compounds, such as. B. water, gelatin, lactose, starch, magnesium stearate, talc, vegetable oils, benzyl alcohols, gum, polyalkylene glycols, petrolatum, cholesterol and other known excipients. The pharmaceutical preparations can be in solid form, e.g. B. as tablets, coated tablets or capsules, or in liquid or semi-liquid form as solutions, suspensions, emulsions, ointments or creams.
If necessary, these pharmaceutical preparations are sterilized and / or 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.
The new compounds can also serve as starting materials for the production of other valuable compounds.
0.455 g of the 1,4-6a, 9a-difluoro-16a-methyl-1 lss, 17a-dihydroxy-21,21-dimethoxy-3,20-dioxo-pregnadiene obtained is dissolved in 25 ml of tetrahydrofuran and 75 ml of 2, 66 molar aqueous perchloric acid. The solution is subjected to slow distillation under reduced pressure for 10 hours, the tetrahydrofuran-water mixture which is distilled off being continuously replaced. The solution is then mixed with 125 ml of water, concentrated in vacuo to remove most of the tetrahydrofuran,
The compounds mentioned can also be used as feed additives.
The invention is described in more detail in the following examples. The temperatures are given in degrees Celsius.
example
100 ml of a 1% solution of hydrogen chloride in methanol are poured over 1.065 g of hydrate des d 1,4-6u, 9a-difluoro-16a-methyl-llss, 17u-dihydroxy-3,20,2 1-trioxo-pregnadiene. After the reaction mixture has been stirred for 16 hours at room temperature, it is evaporated in vacuo, the crude dimethylacetal is taken up in methylene chloride and the solution is filtered through a column of 25 g of aluminum oxide (activity IV). The eluates obtained with methylene chloride-ether (1: 1) are combined and concentrated in vacuo. Upon careful addition of ether, 1,4-6a, 9a-difluoro-16a-methyl-1 lss, 17a-dihydroxy-2 1,2 1-dimethoxy-3, 20-dioxo-pregnadiene separates.
whereupon the hydrate of zl 14-6a, 9a-difluoro-16a-methyl-1 lss, 17a-dihydroxy-3,20,21-trioxo-pregnadiene precipitates.
0.328 g of the aldehyde hydrate obtained is dissolved in 30 ml of methanol and, after adding 0.03 ml of glacial acetic acid and diluting with 120 ml of water, concentrated to a residual volume of 12.5 ml. In this way, the d 1,4-6a, 9a-difluoro-16a-methyl-11ss, 17a-dihydroxy-3,20,21-trioxo-pregnadiene in the form of the 21-methyl-hemiacetal from F. 129- 135.
PATENT APPLICATION
Process for the production of 21-aldehyde acetals or
Hemiacetals of the pregnancy series of the formula
EMI2.1
wherein R1 and R2 are hydroxyl groups, of which at least one is etherified, characterized in that 21-aldehydes or their hydrates or hemiacetals of the formula
EMI2.2
wherein R3 and R4 represent hydroxyl groups, of which at most one can be etherified, or R3 together with R4 represent an oxo group, treated with etherifying agents.
SUBCLAIMS
1. The method according to claim, characterized in that alcohols are used as etherifying agents.
2. The method according to claim, characterized in that alcohols are used in the presence of an acidic catalyst.
3. The method according to claim or one of the dependent claims 1-2, characterized in that alcohols having 1-8 carbon atoms are used.
4. The method according to claim or one of the dependent claims 1-2, characterized in that dihydric alcohols are used.
5. The method according to claim or one of the dependent claims 1-2, characterized in that methyl alcohol is used.
6. The method according to claim, characterized in that orthoformic acid esters of the alcohols in question are used as etherifying agents.
** WARNING ** End of DESC field could overlap beginning of CLMS **.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH851671A CH545776A (en) | 1966-12-09 | 1966-12-09 | 21-Aldehydes of the pregnane series - anti-inflammatory, thymolytic, anti-leukaemia intermediates |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH851671A CH545776A (en) | 1966-12-09 | 1966-12-09 | 21-Aldehydes of the pregnane series - anti-inflammatory, thymolytic, anti-leukaemia intermediates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH545776A true CH545776A (en) | 1966-12-09 |
Family
ID=4341431
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH851671A CH545776A (en) | 1966-12-09 | 1966-12-09 | 21-Aldehydes of the pregnane series - anti-inflammatory, thymolytic, anti-leukaemia intermediates |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH545776A (en) |
-
1966
- 1966-12-09 CH CH851671A patent/CH545776A/en not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |