CH511824A - Anti-inflammatory steroids - Google Patents
Anti-inflammatory steroidsInfo
- Publication number
- CH511824A CH511824A CH874071A CH874071A CH511824A CH 511824 A CH511824 A CH 511824A CH 874071 A CH874071 A CH 874071A CH 874071 A CH874071 A CH 874071A CH 511824 A CH511824 A CH 511824A
- Authority
- CH
- Switzerland
- Prior art keywords
- alpha
- compound
- formula
- diene
- steroido
- Prior art date
Links
- 150000003431 steroids Chemical class 0.000 title abstract description 5
- 230000003110 anti-inflammatory effect Effects 0.000 title description 2
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- 125000003118 aryl group Chemical group 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 6
- 150000001728 carbonyl compounds Chemical class 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004423 acyloxy group Chemical group 0.000 abstract 1
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract 1
- 239000002260 anti-inflammatory agent Substances 0.000 abstract 1
- 125000001589 carboacyl group Chemical group 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 150000002367 halogens Chemical class 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- -1 oxygen ketone Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0036—Nitrogen-containing hetero ring
- C07J71/0057—Nitrogen and oxygen
- C07J71/0068—Nitrogen and oxygen at position 16(17)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
- C07J41/0011—Unsubstituted amino radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
(A) Steroids of general formulae (I) and (II); and their analogues (Ia), (IIa), (Ib) and (IIb) - where R1=H, carboxylic acyl (in I and II); H, OH and acyloxy (in Ia and IIa) - Z, Z'=CHOH or C=O; R=H, alkyl, aryl; X=H or halogen. - 17alpha-amino-9alpha-fluoro-11beta, 16alpha, 21-trihydroxy-pregna-1,4-diene-3,20-dione and its 21-benzoate; etc. - As anti-inflammatory agents.
Description
Procédé de préparation de nouveaux stéroïdes La présente invention a pour objet un procédé de préparation d'une stéroïdo-oxazolidinooxazine de for mule partielle I
EMI0001.0002
caractérisé en ce que l'on met en contact une stéroïdo- oxazolidine de formule partielle II o
EMI0001.0005
avec un composé carbonylé de formule R-CO-R ou un acétal de ce composé, dans lesquelles formules les symboles R, identiques ou différents, représentent cha cun un atome d'hydrogène ou un groupe alcoyle infé rieur ou aryle. On peut conduire la condensation en présence d'eau ou dans des conditions anhydres,
à une et 100 C et plus lorsque température comprise entre 0 le dérivé fonctionnel du composé carbonyle bout au- dessus de 100 C sans décomposition. Le cours de 1a réaction est fortement influencé par la grandeur des groupes présents dans le composé carbo nyle. En d'autres termes, l'empêchement stérique des groupes alcoyle et aryle R peut jouer un rôle dans la formation des stéroïdo-oxazolidinooxazines I. En fait, lorsqu'au moins un des symboles R est un atome d'hy drogène, le traitement avec un composé carbonyle donne toujours la stéroïdo-oxazolidinooxazine attendue.
noyau D présente la formule I Les composés dont peuvent avoir une grande diversité de structures dans les trois autres noyaux du noyau stéroïde. Par exemple, une ou plusieurs doubles liaisons peuvent être présentes dans les positions 1, 4, 6, 9 (11). Des groupes oxygénés, tels qu'un oxygène cétonique ou un groupe hydroxyle peu vent être présents dans les positions 3 et/ou 11. Il est aussi possible de conduire 1a réaction décrite plus haut sur des stéroïdes portant un substituant 9-halogéno.
Les nouveaux composés décrits ici présentent des propriétés pharmacologiques utiles. Plus particulière ment, ils présentent une activité anti-inflammatoire très élevée.
Cette activité est partagée par pratiquement tous les composés ayant la formule générale suivante
EMI0001.0014
dans laquelle les symboles R, identiques ou différents, représentent un atome d'hydrogène, un groupe alcoyle inférieur ou aryle et une ou deux fonctions oxygénées peuvent être présentes dans les positions 3 et/ou 11, un atome d'halogène peut être présent en position 9 et des doubles liaisons peuvent exister entre les positions 1, 2 et ou 4, 5 et/ou 9, 11.
Les stéroïdo-oxazolidines de formule partielle II, qui sont nécessaires comme matières de départ dans le pro cédé selon l'invention et qui sont des composés nou veaux, peuvent être obtenues selon le procédé et l'utili sation qui font l'objet du brevet suisse No 511823.
Les exemples qui suivent illustrent l'invention Exemple <I>1:</I> Préparation de la 9α-fluoro-11ss-hydroxyandrosta-1,4 diène-3-one-[17α,16α-d]-oxazolidino-[3',4'-c]-2''- méthyl-2H-tétrahydro-1,3-oxazin-5'-one On maintient un mélange de 11 g de 11ss,21-dihydro- oxy - 9α - fluoropregna-1,4-diène-3,20-dione-[17α,16α-d]- oxazolidine, 50 ml d'eau et 60 ml d'acétaldéhyde à 0r, C pendant 2 heures, puis additionne 100 ml d'eau et extrait le mélange à l'acétate d'éthyle. Après avoir éva poré le solvant, on cristallise le résidu dans le méthanol.
Le composé est la 9α-fluoro-11ss-hydroxyandrosta-1,4- diène- 3 - one-[17α,16α-d]-oxazolidino-[3',4'-c]-2''-méthyl- 2H-tétrahydro-1,3-oxazin-5'-one qui fond à 248-249C.
<I>Exemple 2:</I> Préparation de la 9α-fluoro-llss-hydroxyandrosta-1,4 diène-3-one-[17α,16α-d]-2'-méthyloxazolidino-[3',4'-c]- 2H-tétrahydro-1,3-oxazin-5''-one On prépare ce composé à partir de la 11ss,21-dihy- droxy-9α-fluoropregna-1,4-diène-3,20-dione-[17α, 16α-d]- 2'-méthyloxazolidino en mélangeant cette dernière avec du formaldéhyde à 36 % et du méthanol à température ordinaire. Le produit obtenu fond à 285o C.
Process for the preparation of new steroids The present invention relates to a process for the preparation of a steroido-oxazolidinooxazine of partial formula I
EMI0001.0002
characterized in that one brings into contact a steroido-oxazolidine of partial formula II o
EMI0001.0005
with a carbonyl compound of formula R-CO-R or an acetal of this compound, in which formulas the symbols R, identical or different, each represent a hydrogen atom or a lower alkyl or aryl group. Condensation can be carried out in the presence of water or under anhydrous conditions,
at one and 100 ° C. and more when the temperature is between 0, the functional derivative of the carbonyl compound boils above 100 ° C. without decomposition. The course of the reaction is strongly influenced by the size of the groups present in the carbonyl compound. In other words, the steric hindrance of the alkyl and aryl groups R may play a role in the formation of steroido-oxazolidinooxazines I. In fact, when at least one of the symbols R is a hydrogen atom, the treatment with a carbonyl compound always gives the expected steroidoxazolidinooxazine.
Ring D has the formula I Compounds of which can have a wide variety of structures in the other three rings of the steroid ring. For example, one or more double bonds can be present in positions 1, 4, 6, 9 (11). Oxygen groups, such as oxygen ketone or a hydroxyl group can be present in the 3 and / or 11 positions. It is also possible to carry out the reaction described above on steroids bearing a 9-halo substituent.
The new compounds described herein exhibit useful pharmacological properties. More particularly, they exhibit very high anti-inflammatory activity.
This activity is shared by virtually all compounds having the following general formula
EMI0001.0014
in which the symbols R, identical or different, represent a hydrogen atom, a lower alkyl or aryl group and one or two oxygen functions may be present in positions 3 and / or 11, a halogen atom may be present in position 9 and double bonds can exist between positions 1, 2 and or 4, 5 and / or 9, 11.
The steroido-oxazolidines of partial formula II, which are necessary as starting materials in the process according to the invention and which are new compounds, can be obtained according to the process and the use which are the subject of the patent. Swiss No 511823.
The following examples illustrate the invention Example <I> 1: </I> Preparation of 9 α -fluoro-11ss-hydroxyandrosta-1,4-diene-3-one- [17 α, 16 α -d] -oxazolidino - [3 ', 4'-c] -2' '- methyl-2H-tetrahydro-1,3-oxazin-5'-one A mixture of 11 g of 11ss, 21-dihydrooxy - 9 α - fluoropregna-1,4-diene-3,20-dione- [17 α, 16 α -d] - oxazolidine, 50 ml of water and 60 ml of acetaldehyde at 0r, C for 2 hours, then add 100 ml of water and extract the mixture with ethyl acetate. After evaporating the solvent, the residue is crystallized from methanol.
The compound is 9 α -fluoro-11ss-hydroxyandrosta-1,4-diene- 3-one- [17 α, 16 α -d] -oxazolidino- [3 ', 4'-c] -2' '- methyl - 2H-tetrahydro-1,3-oxazin-5'-one which melts at 248-249C.
<I> Example 2: </I> Preparation of 9 α -fluoro-llss-hydroxyandrosta-1,4-diene-3-one- [17 α, 16 α -d] -2'-methyloxazolidino- [3 ', 4'-c] - 2H-tetrahydro-1,3-oxazin-5 '' - one This compound is prepared from 11ss, 21-dihy-droxy-9 α -fluoropregna-1,4-diene-3, 20-dione- [17 α, 16 α -d] - 2'-methyloxazolidino by mixing the latter with 36% formaldehyde and methanol at room temperature. The product obtained melts at 285o C.
Claims (1)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT1602968 | 1968-05-03 | ||
| CH673969A CH511823A (en) | 1968-05-03 | 1969-05-02 | Process for the preparation of new steroids |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH511824A true CH511824A (en) | 1971-08-31 |
Family
ID=25700085
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH874071A CH511824A (en) | 1968-05-03 | 1969-05-02 | Anti-inflammatory steroids |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH511824A (en) |
-
1969
- 1969-05-02 CH CH874071A patent/CH511824A/en not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |