GB1030304A - Pregnane [3,2-c] pyrazoles - Google Patents
Pregnane [3,2-c] pyrazolesInfo
- Publication number
- GB1030304A GB1030304A GB7669/63A GB766963A GB1030304A GB 1030304 A GB1030304 A GB 1030304A GB 7669/63 A GB7669/63 A GB 7669/63A GB 766963 A GB766963 A GB 766963A GB 1030304 A GB1030304 A GB 1030304A
- Authority
- GB
- United Kingdom
- Prior art keywords
- prepared
- acyloxy
- dione
- hydrogen
- compounds
- 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.)
- Expired
Links
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
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- 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
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J21/00—Normal steroids containing carbon, hydrogen, halogen or oxygen having an oxygen-containing hetero ring spiro-condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J21/005—Ketals
- C07J21/006—Ketals at position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/0026—Oxygen-containing hetero ring cyclic ketals
- C07J71/0031—Oxygen-containing hetero ring cyclic ketals at positions 16, 17
-
- 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
- C07J71/0042—Nitrogen only
- C07J71/0047—Nitrogen only at position 2(3)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
Abstract
Novel steroids of the formulae <FORM:1030304/C2/1> <FORM:1030304/C2/2> (wherein R1 is hydrogen, fluorine, iodine, hydroxy, acyloxy, tetrahydropyranyloxy, methylsulphonyloxy or a dihydrogen phosphate radical or its alkali metal salt; R is hydrogen or an acyl, alkyl, aralkyl, cycloalkyl, aryl or heterocyclic radical which may be substituted; X is hydrogen or fluorine; Y is hydrogen, chlorine, fluorine or methyl; and the D 6-double bond is optional) and their 16a ,17a -acetals and ketals with aldehydes and ketones P.CO.Q (wherein P and Q are hydrogen, alkyl or aryl or are joined to form an alkylene chain) and salts thereof are prepared by reacting an 11-keto-16a ,17a -dihydroxy-21-acyloxy-4-pregnene-3,20-dione 20-ethylene ketal (which may also be substituted by the groups X and Y and a D 6 double bond) with an alkyl formate and sodium hydride to give the corresponding 2-hydroxymethylene derivative or its formate esters (the 21-acyloxy group is first hydrolysed), reacting this or the corresponding 2-alkoxymethylene compound (prepared by reaction with an alkanol and an acid catalyst) with hydrazine or a substituted hydrazine to give the [3,2-c] pyrazolo-steroid, removing any formate ester groups by treatment with sodium methoxide in methanol, reducing the 11-keto group to an 11b -hydroxy group, and removing the 20-ketal group with acid. Alternatively the side-chain may be protected by converting an 11b ,16a ,17a -trihydroxy - 21 - acyloxy - 4 - pregnene - 3,20 - dione starting material to the corresponding 21-hydroxy - 16a ,17a - acetal or ketal, converting this to the 21-tetrahydropyranyl ether, then converting this to the (3, 2-C) pyrazolo-steroid, and removing the 21-tetrahydropyranyl group and, if desired, the 16, 17-acetal or ketal grouping. The precise structure of the pyrazolo-steroid product, i.e. isomers when R is other than hydrogen, depends on whether the starting material is a 2-hydroxymethylene or 2-acyloxy-methylene compound, and the isomers may be separated by chromatography. Products may be converted to other 16,17-acetals or ketals. They may also be converted to 21-acylates, and if 2 equivalents of an acylating agent are used on the N-unsubstituted compounds, the N-acyl-21-acylates are formed, from which the N-acyl group is selectively removed by heating with acetic acid. 21-Desoxy compounds may be prepared by converting the 21-ol (in which the N-atom is substituted and the 16,17-diol grouping is converted to an acetal or ketal) to the 21, mesylate, converting this to the 21-iodo steroid and reacting this with an alkali metal bisulphite. If the N-unsubstituted compound is used, this is converted to the 21-tetrahydropyranyl ether, this is N-acylated, the ether group is removed and the 21-ol converted to the 21-desoxy compound, and the N-acyl group finally removed. The 21-fluoro compounds are prepared by heating the 21-mesylates with alkali metal fluorides; and the 21-dihydrogen phosphate esters are prepared from the 21-iodo compounds, silver phosphate and phosphoric acid, may be converted to the mono- or dialkali metal salts, from which the free phosphates may be obtained by contact with an ion-exchange resin. 21-Acyloxy starting materials and products may be hydrolysed to the corresponding 21-ols. Numerous examples are given. 11 - Keto - 16a ,17a - dihydroxy - 21 - acyloxy - 4 - pregnene - 3,20 - dione 20 - ethylene ketal compounds are prepared by converting 11b ,17a ,-21 - trihydroxy - 4 - pregnene - 3,20 - dione (which may be substituted by the groups X and Y) to the corresponding 21-acyloxy-D 5-3,20-bisethylene ketal, oxidizing this to the 11-ketone, dehydrating this to the D 16-derivative, hydroxylating this to the 16a ,17a -dihydroxy compound, and reconverting this to the D 4-3-one. 9a - Fluoro - 11b ,21 - dihydroxy - 16a ,17a - isopropylidenedioxy - 4,6 - pregnadiene - 3,20 - dione 21-acetate is prepared from the corresponding D 4-tetrol by reaction successively with acetone, acetic anhydride and chloranil. Similarly are prepared 11b ,21-dihydroxy-6-methyl-16a ,17a -isopropylidenedioxy - 4,6 - pregnadiene 3,20 - dione 21-acetate and the 9a -fluoro derivative thereof. 6 - Chloro - 11b ,21 - dihydroxy - 16a ,17a - isopropylidenediox - 4,6 - pregnadiene - 3,20 - dione 21-acetate is prepared from the corresponding 6-unsubstituted compound via the 6a ,7a -epoxide. The 9a -fluoro-6-chloro compound is prepared similarly. The 6-fluoro compounds are prepared similarly via the epoxides and D 4-6b -fluoro 7a -hydroxy compounds. Steroids of the above general formulaeae wherein R1 is hydrogen, fluorine, hydroxy, acyloxy or a dihydrogen phosphate or its alkali metal salts are stated to have anti-inflammatory activity, and may be made up into pharmaceutical compositions with suitable diluents, carriers or coatings.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US177169A US3072640A (en) | 1962-03-05 | 1962-03-05 | 16-oxygenated-4-pregneno-[3, 2-c] pyrazoles and process of preparing them |
US177169A US3072641A (en) | 1962-03-05 | 1962-03-05 | 16-oxygenated-4-pregneno-[3, 2-c] pyrazoles and process of preparing them |
US177169A US3072639A (en) | 1962-03-05 | 1962-03-05 | 16-oxygenated-4-pregneno-[3, 2-c] pyrazoles and process of preparing them |
US177169A US3072642A (en) | 1962-03-05 | 1962-03-05 | 16-oxygenated-4-pregneno-[3, 2-c] pyrazoles and process of preparing them |
Publications (1)
Publication Number | Publication Date |
---|---|
GB1030304A true GB1030304A (en) | 1966-05-18 |
Family
ID=27497228
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB7669/63A Expired GB1030304A (en) | 1962-03-05 | 1963-02-26 | Pregnane [3,2-c] pyrazoles |
Country Status (7)
Country | Link |
---|---|
BE (1) | BE629171A (en) |
BR (1) | BR6347344D0 (en) |
CH (1) | CH454843A (en) |
DE (1) | DE1468243A1 (en) |
FI (1) | FI40461B (en) |
FR (1) | FR3086M (en) |
GB (1) | GB1030304A (en) |
-
1963
- 1963-02-22 DE DE19631468243 patent/DE1468243A1/en active Pending
- 1963-02-26 GB GB7669/63A patent/GB1030304A/en not_active Expired
- 1963-03-01 FI FI0402/63A patent/FI40461B/fi active
- 1963-03-04 CH CH273563A patent/CH454843A/en unknown
- 1963-03-04 BE BE629171A patent/BE629171A/fr unknown
- 1963-03-04 BR BR147344/63A patent/BR6347344D0/en unknown
- 1963-05-27 FR FR936097A patent/FR3086M/en not_active Expired
Also Published As
Publication number | Publication date |
---|---|
BR6347344D0 (en) | 1973-08-28 |
BE629171A (en) | 1963-09-04 |
CH454843A (en) | 1968-04-30 |
DE1468243A1 (en) | 1969-07-24 |
FI40461B (en) | 1968-10-31 |
FR3086M (en) | 1965-02-26 |
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