US3524850A - Methylalkanoyloxymethyl ketals of prednisolone derivatives - Google Patents
Methylalkanoyloxymethyl ketals of prednisolone derivatives Download PDFInfo
- Publication number
- US3524850A US3524850A US610010A US3524850DA US3524850A US 3524850 A US3524850 A US 3524850A US 610010 A US610010 A US 610010A US 3524850D A US3524850D A US 3524850DA US 3524850 A US3524850 A US 3524850A
- Authority
- US
- United States
- Prior art keywords
- ketals
- methylalkanoyloxymethyl
- oxyacetonide
- derivatives
- prednisolone derivatives
- 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 - Lifetime
Links
- 150000003116 prednisolone derivatives Chemical class 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 description 11
- 230000003110 anti-inflammatory effect Effects 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 229960005294 triamcinolone Drugs 0.000 description 6
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 206010018691 Granuloma Diseases 0.000 description 3
- 150000001241 acetals Chemical class 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 239000003246 corticosteroid Substances 0.000 description 3
- 229960001334 corticosteroids Drugs 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 229940043075 fluocinolone Drugs 0.000 description 2
- FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- HGTYBQOCNLPOHZ-UHFFFAOYSA-N 2-oxopropyl hexanoate Chemical compound CCCCCC(=O)OCC(C)=O HGTYBQOCNLPOHZ-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- UVHJXJNIKLIFDW-UHFFFAOYSA-N C(C)(=O)OCC([CH2-])=O Chemical compound C(C)(=O)OCC([CH2-])=O UVHJXJNIKLIFDW-UHFFFAOYSA-N 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001887 cortisones Chemical class 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- -1 methyl-butyroyloxyacetonide Chemical compound 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J75/00—Processes for the preparation of steroids in general
Definitions
- X is H or F and R is an alyl group having 3 to 5 carbon atoms possess anti-inflammatory action.
- This invention relates to anti-inflammatory steroids, particularly prednisolone derivatives. It particularly relates to alkylalkanoyloxy alkyl ketals of fiuorinated prednisolone derivatives.
- alkylalkanoyloxyalkyl ketals of prednisolone derivatives have provide to have good anti-inflammatory effect, particularly when the alkanoyl group contains 1-2 carbon atoms. Tests with other acetals and ketals have shown that the number of carbon atoms in the acetal and ketal group should be low.
- Known methylalkanoyloxymethyl ketals are described in e.g. the British Pat. No. 1,020,309 and the Belgian Pat. No. 660,549.
- the compound according to the present invention has the following general formula:
- R is an alkyl group which has at least 3 carbon atoms and not more than 5 cabon atoms
- X designates hydrogen or fluorine
- EXAMPLE 1 To a suspension of 300 mg. of triamcinolon in 7.5 ml. of dioxane (dried and newly distilled), 2.5 g. of caproyloxy-acetone and 25 mg. of perchloric acid are added. The reaction mixture is stirred at 20-30" C. in nitrogen gas atmosphere for 5 hours. Gradually, a homogeneous, acid solution is formed, which is neutralized with a 5% sodium bicarbonate solution to pH 6.5. The solution is extracted with chloroform, after which the chloroform layer is dried and evaporated in vacuum. The reaction is re-crystallized from approx. 10 ml. of a mixture of ethyl acetate and ligroin in the proportion 1:1. Triamcinolone caprolyoxyacetonide is obtained, with a yield of 82% and a melting point of 229-230 C.
- TAB LE Granulom weight in percent of granulom Daily weight of dose in Number reference No. Corticosteriod mg. of animals animals 1 Triameinolone acetyl- 10 48 69 oxyacetonide. 2 Triameinolone butyroyl- 10 8 67 oxyaeetonide. 3 Triameinolone valeroyl- 10 8 50 oxyacetonide. 4 Triamcinolone caproyl- 10 8 64 oxyacetonide. 5 Triamcinolone-3,3-di- 10 methyl-butyroyloxyacetonide. 6 Fluocinolone valeroyl- 10 8 62 oxyacetonide. 7 Triamcinolone acetyl- 3.
- valeroyl- 4 A compound of the formula oxyacetonides have a considerably better anti-inflammatory effect compared with the other compounds.
- a compound of the formula: 5 '-----O 0 0 cnr-o- -cim on 0 0/ cm-o-fi-m References Cited 15 UNITED STATES PATENTS 3,048,581 8/1962 Fried 260-23955 wherein R is an alkyl group containing from 4-5 car- 3,341,526 9/ 1967 Af Ekenstam 260-23955 bon atoms and X is hydrogen or fluorine.
- R 20 LEWIS GOTTS Pnmary Examiner butyl. E. G. LOVE, Assistant Examiner 3.
- R is amyl. US. Cl. X.R.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE1048/66A SE307576B (de) | 1966-01-27 | 1966-01-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3524850A true US3524850A (en) | 1970-08-18 |
Family
ID=20257516
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US610010A Expired - Lifetime US3524850A (en) | 1966-01-27 | 1967-01-18 | Methylalkanoyloxymethyl ketals of prednisolone derivatives |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US3524850A (de) |
| AT (1) | AT269385B (de) |
| BE (1) | BE692983A (de) |
| CH (1) | CH487872A (de) |
| DE (1) | DE1618028A1 (de) |
| ES (1) | ES336470A1 (de) |
| FR (1) | FR6257M (de) |
| GB (1) | GB1120337A (de) |
| GR (1) | GR33327B (de) |
| NL (1) | NL6700465A (de) |
| SE (1) | SE307576B (de) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101451486B1 (ko) * | 2009-09-11 | 2014-10-22 | 키에시 파르마슈티시 엣스. 피. 에이. | N-치환된 이속사졸리딘 링과 함께 16, 17 위치 내에 응축된 항염증제로서의 프레그난 유도체 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3048581A (en) * | 1960-04-25 | 1962-08-07 | Olin Mathieson | Acetals and ketals of 16, 17-dihydroxy steroids |
| US3341526A (en) * | 1965-01-12 | 1967-09-12 | Bofors Ab | Acyloxyacetals of fluoro-16alpha-hydroxyprednisolones |
-
1966
- 1966-01-27 SE SE1048/66A patent/SE307576B/xx unknown
-
1967
- 1967-01-05 DE DE19671618028 patent/DE1618028A1/de active Pending
- 1967-01-12 NL NL6700465A patent/NL6700465A/xx unknown
- 1967-01-18 US US610010A patent/US3524850A/en not_active Expired - Lifetime
- 1967-01-19 AT AT52967A patent/AT269385B/de active
- 1967-01-20 BE BE692983D patent/BE692983A/xx unknown
- 1967-01-24 CH CH101267A patent/CH487872A/de not_active IP Right Cessation
- 1967-01-24 ES ES336470A patent/ES336470A1/es not_active Expired
- 1967-01-25 GR GR670133327A patent/GR33327B/el unknown
- 1967-01-26 FR FR92659A patent/FR6257M/fr not_active Expired
- 1967-01-26 GB GB3976/67A patent/GB1120337A/en not_active Expired
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3048581A (en) * | 1960-04-25 | 1962-08-07 | Olin Mathieson | Acetals and ketals of 16, 17-dihydroxy steroids |
| US3341526A (en) * | 1965-01-12 | 1967-09-12 | Bofors Ab | Acyloxyacetals of fluoro-16alpha-hydroxyprednisolones |
Also Published As
| Publication number | Publication date |
|---|---|
| GB1120337A (en) | 1968-07-17 |
| ES336470A1 (es) | 1970-04-01 |
| GR33327B (el) | 1967-11-23 |
| NL6700465A (de) | 1967-07-28 |
| SE307576B (de) | 1969-01-13 |
| DE1618028A1 (de) | 1970-10-29 |
| AT269385B (de) | 1969-03-10 |
| BE692983A (de) | 1967-07-03 |
| FR6257M (de) | 1968-08-19 |
| CH487872A (de) | 1970-03-31 |
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