Claims
- 1. A compound according to the formula ##STR3## in which X is H, Hal or CH.sub.3 COO-; R.sub.1 is CU.sub.3 (CH.sub.2).sub.2 CH-; and R.sub.2 and R.sub.3 are separately H or Hal.
- 2. A pharmaceutical composition having anti-inflammatory properties comprising as the active ingredient an effective amount of a compound according to claim 1 together with a pharmaceutically acceptable carrier.
- 3. A method of treating inflammatory conditions which comprises administering to a patent an anti-inflammatory effective amount of a composition according to claim 2.
- 4. 9.alpha.-Fluoro-21-chloro-16.alpha.,17.beta.-butylidenedioxy-11.beta.-hydroxypregna-4-ene-3,20-dione.
- 5. A pharmaceutical composition having antiinflammatory properties comprising as the active ingredient an effective amount of the compound according to claim 4 together with a pharmaceutically acceptable carrier.
- 6. A method of treating inflammatory conditions which comprises administering to a patient an anti-inflammatory effective amount of a composition according to claim 5.
- 7. 6.alpha.-Fluoro-16.alpha.,17.beta.-butylidenedioxy-11.alpha.,21-dihydroxypregna-4-ene-3,20-dione.
- 8. A pharmaceutical composition having antiinflammatory properties comprising as the active ingredient an effective amount to the compound according to claim 7 together with a pharmaceutically acceptable carrier.
- 9. A method of treating inflammatory conditions which comprises administering to a patient an anti-inflammatory effective amount of a composition according to claim 8.
- 10. 9.alpha.-fluoro-16.alpha.,17.alpha.-butylidenedioxy-11.beta.,21-dihydroxypregna-4-ene-3,20-dione.
- 11. A pharmaceutical composition having anti-inflammatory properties comprising as the active ingredient an effective amount of the compound according to claim 10 together with a pharmaceutically acceptable carrier.
- 12. A method of treating inflammatory conditions which comprises administering to a patient an anti-inflammatory effective amount of a composition according to claim 11.
- 13. 6.alpha.-Fluoro-9.alpha.-chloro-16.alpha.,17.beta.-butylidenedioxy-11.beta.-hydroxy, 21-acetoxy-pregna-4-ene-3,20-dione.
- 14. A pharmaceutical composition having antiinflammatory properties comprising as the active ingredient an effective amount of the compound according to claim 13 together with a pharmaceutically acceptable carrier.
- 15. A method of treating inflammatory conditions which comprises administering to a patient an anti-inflammatory effective amount of a composition according to claim 14.
Priority Claims (1)
| Number |
Date |
Country |
Kind |
| 21343 A/84 |
Jun 1984 |
ITX |
|
Parent Case Info
This application is a continuation-in-part of appl. ser. no. 739,131 filed May 30, 1985, now U.S. Pat. No. 4,695,625.
The present invention relates to 16,17 acetals of pregnane derivatives and to pharamceutical compositions containing them.
The 16,17 acetals of pregnane derivatives according to this invention have the following general formula: ##STR2## wherein R.sub.1 is CH.sub.3 (CH.sub.2).sub.2 CH--, R.sub.2 and R.sub.3 are separately selected from H and Hal, and X is H, Hal or CH.sub.3 COO--. Specifically, the compounds according to this invention are the following:
6.alpha.-fluoro-16.alpha.,17.beta.-butylidenedioxy-11.beta.,21-dihydroxypregna-4-ene-3,20-dione;
960 -fluoro-16.alpha.,17.alpha.-butylidenedioxy-11.beta.,21-dihydroxypregna-4-ene-3,20-dione;
6.alpha.-fluoro-9.alpha.-chlor0-16.alpha.,17.alpha.-butylidenedioxy-11.beta.-hydroxy,
21-acetoxy-pregna-4-ene-3,20-dione.
The compounds of this invention can be prepared by reacting 16,17-acetonides with aldhydes having the formula R.sub.1 CHO, in which R.sub.1 has the meaning given above, in molar ratios ranging from 1:1 to 1:5, preferably from 1:1 to 1:1.1, in aqueous hydrofluoric acid and concentrations ranging from 20 to 90%, preferably from 50 to 70%, at a temperature from -70.degree. to 20.degree. C., the temperature being choosen in order to give the desired epimer ratio.
The product is isolated by simple water dilution, in high purity.
Although working with unitary stoichiometric ratios between the steroidal substrate and the carbonyl compound, the reaction takes place in almost quantitative yields.
Alternatively, instead of hydrofluoric acid, it is possible to use hydrochloric acid. In this case, however, the reaction is less selective in the isomers ratio and the product obtained is less pure.
It should be noted that the acetonide can be replaced by the corresponding diol derivative. Under these conditions the acetal is always produced with an excess of the B epimer, but with a lower selectivity.
Another aspect of the invention, equally important, concerns the conversion of the less active epimer of a 16,17-acetal into the more active epimer. For instance, a mixture of budesonide containing only 30% of the B epimer, subjected to the above mentioned conditions for the preparation of budesonide from the corresponding acetonide, is transformed into budesonide having more than 90% of B epimer. This process is very useful to recover active product from the mother liquors (as deriving from the crystallization) enriched in A epimer. For the epimerization of budesonide like compounds it is sufficient the treatment with hydrofluoric acid alone but, usually, an amount (lower than the stoichiometric one) of the aldehyde (in the instance of budesonide, butyraldehyde) is added in order to avoid any formation of the 16,17-diol.
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Date |
Kind |
|
3929768 |
Brattsand et al. |
Dec 1975 |
|
|
3983233 |
Brattsand et al. |
Sep 1976 |
|
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3996359 |
Brattsand et al. |
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|
Continuation in Parts (1)
|
Number |
Date |
Country |
| Parent |
739131 |
May 1989 |
|
Patent Grant
4835145
