EP1140912A1 - Process for the preparation of an acetate salt of paroxetine or paroxetine analogues - Google Patents
Process for the preparation of an acetate salt of paroxetine or paroxetine analoguesInfo
- Publication number
- EP1140912A1 EP1140912A1 EP99962415A EP99962415A EP1140912A1 EP 1140912 A1 EP1140912 A1 EP 1140912A1 EP 99962415 A EP99962415 A EP 99962415A EP 99962415 A EP99962415 A EP 99962415A EP 1140912 A1 EP1140912 A1 EP 1140912A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- compound
- acetic acid
- paroxetine
- salt
- disorders
- 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.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
Definitions
- the present invention relates to a new process for preparing pharmaceutically active compounds and intermediates therefor.
- paroxetine is obtained from a toluene solution via an intermediate aqueous solution of the acetate.
- solid paroxetine acetate is isolated by addition of an excess of acetic acid and diethyl ether to an ether solution of the free base.
- diethyl ether is hazardous, particularly in a manufacturing environment, due to its very high flammability and potential for explosive residues, especially during drying procedures. Consequently, manufacturing scale operation would involve expensive precautions and specialised apparatus, adding greatly to operating and capital costs. Furthermore, diethyl ether is not a convenient solvent for the manufacture of paroxetine free base. In the literature, toluene is typically used to manufacture the free base, but a distillation step is required to isolate the base and as a result it is produced in the form of a heavy viscous syrup. This distillation step is an inconvenient additional process and adds further to the production costs.
- the present invention provides a process for the preparation of an acetate salt of a compound of formula (1):
- R 1 is a substituted phenyl group, preferably 3,4-methylenedioxyphenyl; the process comprising contacting a solution of the compound of formula (1) with an amine acetic acid salt.
- the amine acetic acid salt is selected from acetic acid salts of ammonia, alkyl amines, aryl amines, aralkyl amines and heterocyclic amines. More preferably, the amine acetic acid salt is selected from acetic acid salts of ammonia, methylamine, dimethylamine, aniline, benzylamine and pyridine. Most preferably, the amine acetic acid salt is ammonium acetate.
- the acetate salt may be recrystallised from alcohols, ketones, esters, acetic acid or ethers.
- Particularly suitable solvents include ethyl acetate, ethanol, propan-1-ol, propan-2-ol, acetone, butanone, and isobutylmethyl ketone, either alone or in combination.
- the recrystallisation step may include, as required, heating, for example including removal of water using Dean & Stark apparatus, treatment with activated charcoal, silica or similar substances used for the removal of impurities, filtration, concentration, cooling and seeding.
- the acetate may be isolated as a solid by evaporation, freeze-drying or spray-drying.
- Spray drying from organic solvents or from mixtures of water with organic solvents are preferred in order to achieve satisfactory drying below the glass point.
- a preferred procedure is evaporation or spray drying directly onto a solid support, particularly one of use as an excipient for the formation of tablets or capsules.
- the process of this invention may be used to prepare active compounds described in US-A-3912743 and US-A-4007196, and preferably to prepare paroxetine hemihydrate.
- solvated, amorphous, or anhydrate products may be isolated according to previously disclosed procedures.
- Paroxetine acetate may be converted to the hydrochloride salt and most preferably the hemihydrate of that salt, as described in EP-A-0223403.
- the present invention includes within its scope the compound paroxetine, particularly paroxetine hydrochloride, especially as the hemihydrate, when obtained via any aspect of this invention, and any novel intermediates resulting from the described procedures.
- Paroxetine is the (-)-trans isomer of 4-(4'-fluorophenyl)-3-(3",4"-methylenedioxy- phenoxymethyl)piperidine.
- optical resolution may be carried out prior to coupling with the phenol.
- resolution may be carried out at other stages, such as after deprotection of the piperidine nitrogen.
- the Reference Example describes two suitable methods of resolution of the N-deprotected compound.
- Paroxetine obtained using this invention may be formulated for therapy in the dosage forms described in EP-A-0223403 or WO96/24595, either as solid formulations or as solutions for oral or parenteral use.
- paroxetine especially paroxetine hydrochloride, obtained using this invention
- the present invention also provides:
- compositions for treatment or prophylaxis of the Disorders comprising paroxetine or paroxetine hydrochloride obtained using the process of this invention and a pharmaceutically acceptable carrier,
- paroxetine or paroxetine hydrochloride obtained using the process of this invention to manufacture a medicament for the treatment or prophylaxis of the Disorders
- a method of treating the Disorders which comprises administering an effective or prophylactic amount of paroxetine or paroxetine hydrochloride obtained using the process of this invention to a person suffering from one or more of the disorders.
- paroxetine acetate Preparation of paroxetine acetate using ammonium acetate.
- the product of the reaction, crystalline paroxetine acetate was isolated by filtration. washed with tetrahydrofuran and dried under vacuum.
- paroxetine acetate 0.5 g
- propan-2-ol 5 ml
- the resulting solution was cooled to 0-5°C for 2 hours resulting in the formation of a white precipitate.
- the solid was collected by filtration, washed with propan-2-ol (1 ml) and dried in vacuo over phosphorous pentoxide to give paroxetine acetate.
- Paroxetine acetate was also recrystallised from propan-1-ol, acetone, butanone, and isobutylmethyl ketone by analogous procedures.
- Paroxetine free base is liberated from the (-) trans 4-(4'-fiuoro-phenyl)-3- (3",4"-methylenedioxyphenoxymethyl)piperidine di-p-toluoyl or dibenzoyl tartrate salt by stirring in a mixture of toluene and dilute aqueous sodium hydroxide. The phases are separated and the toluene phase washed with water. Concentrated aqueous hydrochloric acid is then added and the crystalline precipitate collected by filtration and dried.
Abstract
The present invention relates to a new process for the preparation of an acetate salt of a compound of formula (1) in which R1 is a substituted phenyl group, preferably 3,4-methylenedioxyphenyl; the process comprising contacting a solution of the compound of formula (1) with an amine acetic acid salt. The (-) trans isomer of 4-(4'-fluorophenyl)-3-(3',4'methylenedioxyphenoxymethyl)-piperidine (paroxetine) is an important compound having antidepressant and anti-Parkinson properties. This compound is used in therapy as the hydrochloride salt to treat inter alia depression, obsessive compulsive disorder (OCD) and panic.
Description
PROCESS FOR THE PREPARAΗON OF AN ACETATE SALT OF PAROXETINE OR PAROXETINE ANALOGUES
The present invention relates to a new process for preparing pharmaceutically active compounds and intermediates therefor.
Pharmaceutical products with antidepressant and anti-Parkinson properties are described in US-A-3912743 and US-A-4007196. An especially important compound among those disclosed is paroxetine, the (-) trans isomer of 4-(4'-fluorophenyl)-3- (3",4"-methylenedioxyphenoxymethyl)piperidine. This compound is used in therapy as the hydrochloride salt to treat inter alia depression, obsessive compulsive disorder (OCD) and panic.
In Example 2 of EP 0 223 403, an earlier application of the present applicant, paroxetine is obtained from a toluene solution via an intermediate aqueous solution of the acetate. In Example 8 of the same disclosure, solid paroxetine acetate is isolated by addition of an excess of acetic acid and diethyl ether to an ether solution of the free base.
The use of diethyl ether is hazardous, particularly in a manufacturing environment, due to its very high flammability and potential for explosive residues, especially during drying procedures. Consequently, manufacturing scale operation would involve expensive precautions and specialised apparatus, adding greatly to operating and capital costs. Furthermore, diethyl ether is not a convenient solvent for the manufacture of paroxetine free base. In the literature, toluene is typically used to manufacture the free base, but a distillation step is required to isolate the base and as a result it is produced in the form of a heavy viscous syrup. This distillation step is an inconvenient additional process and adds further to the production costs.
Accordingly, there is a need for a process for the preparation of acetate salts of paroxetine and its analogues which is suitable for large scale manufacture.
In its broadest sense, the present invention provides a process for the preparation of an acetate salt of a compound of formula (1):
in which R1 is a substituted phenyl group, preferably 3,4-methylenedioxyphenyl; the process comprising contacting a solution of the compound of formula (1) with an amine acetic acid salt.
Preferably, the amine acetic acid salt is selected from acetic acid salts of ammonia, alkyl amines, aryl amines, aralkyl amines and heterocyclic amines. More preferably, the amine acetic acid salt is selected from acetic acid salts of ammonia, methylamine, dimethylamine, aniline, benzylamine and pyridine. Most preferably, the amine acetic acid salt is ammonium acetate.
Following preparation of the acetate salt, it may be recrystallised from alcohols, ketones, esters, acetic acid or ethers. Particularly suitable solvents include ethyl acetate, ethanol, propan-1-ol, propan-2-ol, acetone, butanone, and isobutylmethyl ketone, either alone or in combination. The recrystallisation step may include, as required, heating, for example including removal of water using Dean & Stark apparatus, treatment with activated charcoal, silica or similar substances used for the removal of impurities, filtration, concentration, cooling and seeding.
Alternatively or additionally, the acetate may be isolated as a solid by evaporation, freeze-drying or spray-drying. Spray drying from organic solvents or from mixtures of water with organic solvents are preferred in order to achieve satisfactory drying below the glass point. A preferred procedure is evaporation or spray drying directly onto a solid support, particularly one of use as an excipient for the formation of tablets or capsules.
The process of this invention may be used to prepare active compounds described in US-A-3912743 and US-A-4007196, and preferably to prepare paroxetine hemihydrate. As an alternative to isolating the hemihydrate, solvated, amorphous, or anhydrate products may be isolated according to previously disclosed procedures.
Paroxetine acetate may be converted to the hydrochloride salt and most preferably the hemihydrate of that salt, as described in EP-A-0223403. The present invention includes within its scope the compound paroxetine, particularly paroxetine hydrochloride, especially as the hemihydrate, when obtained via any aspect of this invention, and any novel intermediates resulting from the described procedures.
Paroxetine is the (-)-trans isomer of 4-(4'-fluorophenyl)-3-(3",4"-methylenedioxy- phenoxymethyl)piperidine. Following the procedure of EP-0 152 273, optical resolution may be carried out prior to coupling with the phenol. Alternatively, resolution may be carried out at other stages, such as after deprotection of the piperidine nitrogen. The Reference Example describes two suitable methods of resolution of the N-deprotected compound.
Paroxetine obtained using this invention may be formulated for therapy in the dosage forms described in EP-A-0223403 or WO96/24595, either as solid formulations or as solutions for oral or parenteral use.
Therapeutic uses of paroxetine, especially paroxetine hydrochloride, obtained using this invention include treatment of: alcoholism, anxiety, depression, obsessive
compulsive disorder, panic disorder, chronic pain, obesity, senile dementia, migraine, bulimia, anorexia, social phobia, pre-menstrual syndrome (PMS), adolescent depression, trichotillomania, dysthymia, and substance abuse, referred to below as "the Disorders".
Accordingly, the present invention also provides:
a pharmaceutical composition for treatment or prophylaxis of the Disorders comprising paroxetine or paroxetine hydrochloride obtained using the process of this invention and a pharmaceutically acceptable carrier,
the use of paroxetine or paroxetine hydrochloride obtained using the process of this invention to manufacture a medicament for the treatment or prophylaxis of the Disorders; and
a method of treating the Disorders which comprises administering an effective or prophylactic amount of paroxetine or paroxetine hydrochloride obtained using the process of this invention to a person suffering from one or more of the disorders.
This invention is illustrated by the following Examples.
Examples
Preparative Example 1
Preparation of paroxetine acetate using ammonium acetate.
A solution of paroxetine free base (2.25 g) in tetrahydrofuran (20 ml) was stirred vigorously at approximately 20°C with ammonium acetate (0.81 g). After 2 hours a white precipitate formed, but stirring was continued for a total of 21 hours. The product of the reaction, crystalline paroxetine acetate, was isolated by filtration. washed with tetrahydrofuran and dried under vacuum.
Preparative Example 2
Recrystallisation of paroxetine from propan-2-ol
A suspension of paroxetine acetate (0.5 g), in propan-2-ol (5 ml) was heated to reflux with vigorous stirring to dissolve. The resulting solution was cooled to 0-5°C for 2 hours resulting in the formation of a white precipitate. The solid was collected by filtration, washed with propan-2-ol (1 ml) and dried in vacuo over phosphorous pentoxide to give paroxetine acetate.
Paroxetine acetate was also recrystallised from propan-1-ol, acetone, butanone, and isobutylmethyl ketone by analogous procedures.
Preparative Example 3
Paroxetine acetate (1 g) was dissolved in water (3 ml) with gentle heating. Isobutylmethyl ketone (15 ml) was added and the solution heated at reflux in a Dean and Stark apparatus until as much water as possible had been removed. The solution was then cooled to 0-5°C and a white crystalline precipitate formed. The solid was collected by filtration, washed with isobutylmethyl ketone and dried to give paroxetine acetate (0. 84 g) as a granular white solid.
Reference Example
Preparation of paroxetine hydrochloride by the resolution of (±) trans 4-(4'- fluorophenyI)-3-(3",4"-methylenedioxyphenoxymethyl)piperidine.
i) (±) trans 4-(4'-fluorophenyl)-3-(3",4"-methylenedioxyphenoxymethyl) piperidine (1.0 g) was dissolved in methanol (10 ml) and added to a solution of L(-)- di-p-toluoyl tartaric acid (1.25g) in methanol (10 ml). The mixture was seeded and allowed to stand at room temperature and the crystalline product examined by chiral HPLC, using the following system:
Chiral HPLC analysis confirmed that substantially pure (-) trans L(-)-di-p-toluoyl tartrate salt had been isolated. The salt may be further purified by recrystallisation from methanol.
ii) (±) trans 4-(4'-fluorophenyl)-3-(3",4"-methylenedioxyphenoxymethyl) piperidine (0.50 g) was dissolved in acetonitrile (10 ml) and added to a solution of L-(-)-dibenzoyl tartaric acid (0.65g) in acetonitrile (10 ml). The mixture was seeded and stirred at room temperature. The crystalline product was shown by chiral HPLC to be significantly enriched with the (-) trans dibenzoyl tartrate salt.
iii) Paroxetine free base is liberated from the (-) trans 4-(4'-fiuoro-phenyl)-3- (3",4"-methylenedioxyphenoxymethyl)piperidine di-p-toluoyl or dibenzoyl tartrate salt by stirring in a mixture of toluene and dilute aqueous sodium hydroxide. The phases are separated and the toluene phase washed with water. Concentrated aqueous hydrochloric acid is then added and the crystalline precipitate collected by filtration and dried.
Claims
1. A process for the preparation of an acetate salt of a compound of formula ( 1 ):
in which R' is a substituted phenyl group, the process comprising contacting a solution of the compound of formula (1) with an amine acetic acid salt.
2. A process as claimed in Claim 1 wherein the amine acetic acid salt is selected from acetic acid salts of ammonia, alkyl amines, aryl amines, aralkyl amines and heterocyclic amines.
3. A process as claimed in Claim 2 wherein the amine acetic acid salt is selected from acetic acid salts of ammonia, methylamine, dimethylamine, aniline, benzylamine and pyridine.
4. A process as claimed in Claim 3 wherein the amine acetic acid salt is ammonium acetate.
5. A process as claimed in any preceding claim wherein the solution of the compound of formula ( 1 ) is in tetrahydrofuran.
6. A process as claimed in any one of Claims 1 to 5 further comprising the step of recrystallisation from an alcohol, ketone, ester, or ether or from acetic acid; or a mixture thereof.
7. A process as claimed in Claim 6 comprising recrystallisation from ethyl acetate, ethanol, propan-1-ol, propan-2-ol, acetone, butanone, or isobutylmethyl ketone, or mixture thereof.
8. A process as claimed in any preceding claim further comprising the step of isolation of the solid by evaporation, freeze-drying or spray-drying.
9. A process as claimed in Claim 8 wherein the solid is isolated from an organic solvent; mixture of organic solvents; or mixture of water with one or more organic solvents.
10. A process as Claimed in Claim 8 or Claim 9 wherein the solid is isolated by evaporation or spray drying directly onto a solid support.
11. A process as claimed in any preceding claim wherein R is 3',4'- methylenedioxyphenyl.
12. A process for preparation of (-)-trαrø-4-(4'-fluorophenyl)-3-(3",4"- methylenedioxyphenoxymethyl)-piperidine that incorporates the process of any one of claims 1 to 11.
13. (-)-tr< s-4-(4'-fiuorophenyl)-3 -(3 " ,4 " -mefhy lenedioxyphenoxymethy 1)- piperidine whenever obtained by a process including the process of any one of claims 1 to 14.
14. (-)-tr rø-4-(4'-fluorophenyl)-3 -(3 " ,4 " -methy lenedioxyphenoxymethyl)- piperidine as claimed in claim 13, in the form of a hydrochloride salt.
15. A pharmaceutical composition for treatment or prophylaxis of the disorders comprising a compound as claimed in claim 13 or 14 and a pharmaceutically acceptable carrier.
16. The use of a compound as claimed in claim 13 or 14 in the manufacture of a medicament for the treatment or prophylaxis of the disorders.
17. A method of treating the disorders which comprises administering an effective or prophylactic amount of a compound as claimed in claim 13 or 14 to a person suffering from one or more of the disorders.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9828781.6A GB9828781D0 (en) | 1998-12-29 | 1998-12-29 | Novel process |
| GB9828781 | 1998-12-29 | ||
| PCT/GB1999/004370 WO2000039123A1 (en) | 1998-12-29 | 1999-12-22 | Process for the preparation of an acetate salt of paroxetine or paroxetine analogues |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1140912A1 true EP1140912A1 (en) | 2001-10-10 |
Family
ID=10845134
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP99962415A Withdrawn EP1140912A1 (en) | 1998-12-29 | 1999-12-22 | Process for the preparation of an acetate salt of paroxetine or paroxetine analogues |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1140912A1 (en) |
| JP (1) | JP2002533459A (en) |
| AU (1) | AU1877300A (en) |
| GB (1) | GB9828781D0 (en) |
| WO (1) | WO2000039123A1 (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0223403B1 (en) * | 1985-10-25 | 1993-08-04 | Beecham Group Plc | Piperidine derivative, its preparation, and its use as medicament |
| SK283394B6 (en) * | 1997-06-10 | 2003-07-01 | Synthon B. V. | 4-phenylpiperidine compounds and its pharmaceutically acceptable salts, process for their preparation, medicament containing them and their use |
-
1998
- 1998-12-29 GB GBGB9828781.6A patent/GB9828781D0/en not_active Ceased
-
1999
- 1999-12-22 JP JP2000591034A patent/JP2002533459A/en active Pending
- 1999-12-22 EP EP99962415A patent/EP1140912A1/en not_active Withdrawn
- 1999-12-22 WO PCT/GB1999/004370 patent/WO2000039123A1/en not_active Application Discontinuation
- 1999-12-22 AU AU18773/00A patent/AU1877300A/en not_active Abandoned
Non-Patent Citations (1)
| Title |
|---|
| See references of WO0039123A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2002533459A (en) | 2002-10-08 |
| WO2000039123A1 (en) | 2000-07-06 |
| AU1877300A (en) | 2000-07-31 |
| GB9828781D0 (en) | 1999-02-17 |
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