US2862938A - 21-(2-chloro-4-nitrobenzoate) of prednisolone and prednisone - Google Patents
21-(2-chloro-4-nitrobenzoate) of prednisolone and prednisone Download PDFInfo
- Publication number
- US2862938A US2862938A US583910A US58391056A US2862938A US 2862938 A US2862938 A US 2862938A US 583910 A US583910 A US 583910A US 58391056 A US58391056 A US 58391056A US 2862938 A US2862938 A US 2862938A
- Authority
- US
- United States
- Prior art keywords
- chloro
- nitrobenzoate
- prednisolone
- prednisone
- pregnadiene
- 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
- 229960005205 prednisolone Drugs 0.000 title description 8
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 title description 8
- 229960004618 prednisone Drugs 0.000 title description 6
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 title description 6
- QAYNSPOKTRVZRC-UHFFFAOYSA-M 2-chloro-4-nitrobenzoate Chemical compound [O-]C(=O)C1=CC=C([N+]([O-])=O)C=C1Cl QAYNSPOKTRVZRC-UHFFFAOYSA-M 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 239000000203 mixture Substances 0.000 description 3
- QQCBOIWDENXRLP-BYZMTCBYSA-N (8s,9s,10r,13r,14s,17s)-17-ethyl-10,13-dimethyl-6,7,8,9,11,12,14,15,16,17-decahydro-3h-cyclopenta[a]phenanthrene Chemical compound C1CC2=CCC=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](CC)[C@@]1(C)CC2 QQCBOIWDENXRLP-BYZMTCBYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000003470 adrenal cortex hormone Substances 0.000 description 2
- ZMOUYPQNOXHFHO-UHFFFAOYSA-N chloro 4-nitrobenzoate Chemical class [O-][N+](=O)C1=CC=C(C(=O)OCl)C=C1 ZMOUYPQNOXHFHO-UHFFFAOYSA-N 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- QIEPWCSVQYUPIY-LEKSSAKUSA-N Delta(1)-progesterone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 QIEPWCSVQYUPIY-LEKSSAKUSA-N 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000002456 anti-arthritic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- NBEMQPLNBYYUAZ-UHFFFAOYSA-N ethyl acetate;propan-2-one Chemical compound CC(C)=O.CCOC(C)=O NBEMQPLNBYYUAZ-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
-
- 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
Definitions
- This invention is concerned with physiologically active steroid hormones and is more particularly concerned with 11fl,l70,21 trihydroxy 1,4 pregnadiene 3,20 dione and 170:,21 dihydroxy 1,4 pregnadiene 3,11,20 trione 21 (2 chloro 4 nitrobenzoates),
- prednisolone and prednisone represented by the following formula:
- the compounds of the present invention are substitutable for other adrenal cortical steroid hormones in known adrenal cortical steroid hormone-containing pharmaceutical compositions such as tablets, lotions, ointments, injectables, and elixirs.
- Other objects and uses of the present invention will be apparent to one skilled in the art.
- the 21-(2-chloro-4-nitrobenzoate) esters of prednisolone and prednisone of the present invention are obtained by esterification of prednisolone and prednisone, respectively, to introduce the 21-(2-chloro-4-nitrobenzoate) radical, as more fully described in the following illustrative examples.
- EXAMPLE 1 A solution of 11 parts of prednisolone in parts of pyridine is prepared at forty degrees centigrade, 8 parts of ortho-chloro-para-nitrobenzoyl chloride is added, with stirring, at a rate to maintain the reaction temperature between twenty and thirty degrees centigrade, and the reaction mixture then stirred for an additional four The mixture is then poured, with stirring into a mixture of 600 parts of ice and water and allowed to stand overnight at five degrees centigrade. The solid which had precipitated is removed by filtration, washed with water, dried, and recrystallized from an ethyl acetateacetone mixture using Nuchar 0-190 N decolorizing charcoal. The yield of purified prednisolone 21-(2- chloro-4-nitrobenzoate) is 63 percent; melting point 195.5 to 198 degrees centigrade; [M is plus 139 degrees in chloroform.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
Description
United States Patent 21-(2-CHLORO-4-NITROBENZOATE) OF PRED- NISOLONE AND PREDNISONE Melvin A. Rebenstorf, Kalamazoo Township, Kalamazoo County, Mich., assignor to The Upjohn Company, Kalamazoo, Mich., a corporation of Michigan No Drawing. Application May 10, 1956 Serial No. 583,910
3 Claims. (Cl. 260-39745) This invention is concerned with physiologically active steroid hormones and is more particularly concerned with 11fl,l70,21 trihydroxy 1,4 pregnadiene 3,20 dione and 170:,21 dihydroxy 1,4 pregnadiene 3,11,20 trione 21 (2 chloro 4 nitrobenzoates),
i. e. the 21 (2 chloro 4 nitrobenzoates) of prednisolone and prednisone represented by the following formula:
01 CE! (I) l on20-b--No1 0:0 ----0H wherein R is selected from the group consisting of p-hydroxy and 0x0.
It is an object of the present invention to provide the 21 (2 chloro 4 nitrobenzoate) of prednisolone and prednisone which are physiologically active agents of high potency having high anti-inflammatory activity, particularly locally and intraarticularly, anti-arthritic activity, low toxicity, and a superior therapeutic ratio. The compounds of the present invention are substitutable for other adrenal cortical steroid hormones in known adrenal cortical steroid hormone-containing pharmaceutical compositions such as tablets, lotions, ointments, injectables, and elixirs. Other objects and uses of the present invention will be apparent to one skilled in the art.
hours.
The 21-(2-chloro-4-nitrobenzoate) esters of prednisolone and prednisone of the present invention are obtained by esterification of prednisolone and prednisone, respectively, to introduce the 21-(2-chloro-4-nitrobenzoate) radical, as more fully described in the following illustrative examples.
EXAMPLE 1 A solution of 11 parts of prednisolone in parts of pyridine is prepared at forty degrees centigrade, 8 parts of ortho-chloro-para-nitrobenzoyl chloride is added, with stirring, at a rate to maintain the reaction temperature between twenty and thirty degrees centigrade, and the reaction mixture then stirred for an additional four The mixture is then poured, with stirring into a mixture of 600 parts of ice and water and allowed to stand overnight at five degrees centigrade. The solid which had precipitated is removed by filtration, washed with water, dried, and recrystallized from an ethyl acetateacetone mixture using Nuchar 0-190 N decolorizing charcoal. The yield of purified prednisolone 21-(2- chloro-4-nitrobenzoate) is 63 percent; melting point 195.5 to 198 degrees centigrade; [M is plus 139 degrees in chloroform.
Analysis.-Theoretical: C, 61.82; H, 5.56. Found: C, 62.09; H, 5.78.
EXAMPLE 2 Found:
"-11;3,17 ,2l trihydroxy 1,4 pregnadiene 3,20 dione 21 (2 chloro 4 nitrobenzoate) and :,21 dihydroxy 1,4 pregnadiene 3,11,20 trione 21 (2 chloro-4-nitrobenzoate) 2. l1fl,17oc,21 trihydroxy 1,4 pregnadiene 3,20 dione 2l-(2-chloro-4-nitrobenzoate).
3. 17o,2l dihydroxy 1,4 pregnadiene 3,11,20 trione 21-(2-chloro-4-nitrobenzoate).
References Cited in the file of this patent UNITED STATES PATENTS Reichstein Dec. 19, 1939 Sarett Feb. 28, 1956
Claims (1)
1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF 11B,17A,21 -TRIHYDROXY - 1,4 - PREGNADIENE - 3,20 - DIONE 21 (2 - CHLORO - 4 - NITROBENZAOATE) AND 17A,21 DIHYDROXY -14 - PREGNADIENE -3,11,20 - TRIONE 21 - (2 CHLORO-4-NITROBENZOATE).
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US583910A US2862938A (en) | 1956-05-10 | 1956-05-10 | 21-(2-chloro-4-nitrobenzoate) of prednisolone and prednisone |
| GB13243/57A GB802566A (en) | 1956-05-10 | 1957-04-25 | Improvements in or relating to a steroid and the manufacture thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US583910A US2862938A (en) | 1956-05-10 | 1956-05-10 | 21-(2-chloro-4-nitrobenzoate) of prednisolone and prednisone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2862938A true US2862938A (en) | 1958-12-02 |
Family
ID=24335107
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US583910A Expired - Lifetime US2862938A (en) | 1956-05-10 | 1956-05-10 | 21-(2-chloro-4-nitrobenzoate) of prednisolone and prednisone |
Country Status (2)
| Country | Link |
|---|---|
| US (1) | US2862938A (en) |
| GB (1) | GB802566A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4086254A (en) * | 1977-04-13 | 1978-04-25 | The Upjohn Company | Photocleavable steroids |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2183589A (en) * | 1939-12-19 | Derivatives of compounds of the | ||
| US2736734A (en) * | 1955-01-14 | 1956-02-28 | Merck & Co Inc | delta1,4-3,20-diketo-11-oxygenated-17,21-dihydroxy-pregnadiene 21-tertiary butyl acetates and 9-fluoro derivatives thereof |
-
1956
- 1956-05-10 US US583910A patent/US2862938A/en not_active Expired - Lifetime
-
1957
- 1957-04-25 GB GB13243/57A patent/GB802566A/en not_active Expired
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2183589A (en) * | 1939-12-19 | Derivatives of compounds of the | ||
| US2736734A (en) * | 1955-01-14 | 1956-02-28 | Merck & Co Inc | delta1,4-3,20-diketo-11-oxygenated-17,21-dihydroxy-pregnadiene 21-tertiary butyl acetates and 9-fluoro derivatives thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4086254A (en) * | 1977-04-13 | 1978-04-25 | The Upjohn Company | Photocleavable steroids |
Also Published As
| Publication number | Publication date |
|---|---|
| GB802566A (en) | 1958-10-08 |
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