[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

WO1998056787A1 - 4-Phenylpiperidine compounds - Google Patents

4-Phenylpiperidine compounds Download PDF

Info

Publication number
WO1998056787A1
WO1998056787A1 PCT/NL1997/000328 NL9700328W WO9856787A1 WO 1998056787 A1 WO1998056787 A1 WO 1998056787A1 NL 9700328 W NL9700328 W NL 9700328W WO 9856787 A1 WO9856787 A1 WO 9856787A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
alkyl
compound according
acid
paroxetine
Prior art date
Application number
PCT/NL1997/000328
Other languages
German (de)
English (en)
French (fr)
Inventor
Franciscus Bernardus Gemma Benneker
Frans Van Dalen
Jacobus Maria Lemmens
Theodorus Hendricus Antonium Peters
Frantisek PÍCHA
Original Assignee
Synthon B.V.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26647319&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO1998056787(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority to EP97926276A priority Critical patent/EP0994872B9/en
Priority to PL97336895A priority patent/PL188450B1/pl
Priority to PCT/NL1997/000328 priority patent/WO1998056787A1/en
Priority to DE29724281U priority patent/DE29724281U1/de
Priority to PT97926276T priority patent/PT994872E/pt
Priority to DE69704679T priority patent/DE69704679T2/de
Priority to EEP199900570A priority patent/EE03970B1/xx
Priority to SI9730138T priority patent/SI0994872T1/xx
Priority to IL13336697A priority patent/IL133366A/xx
Priority to CZ19994295A priority patent/CZ295301B6/cs
Priority to ES97926276T priority patent/ES2155995T3/es
Priority to KR1019997011625A priority patent/KR100543614B1/ko
Priority to JP50212699A priority patent/JP2002503248A/ja
Priority to TR1999/03025T priority patent/TR199903025T2/xx
Priority to EEP200200633A priority patent/EE200200633A/xx
Application filed by Synthon B.V. filed Critical Synthon B.V.
Priority to HU0003141A priority patent/HUP0003141A3/hu
Priority to TR2002/01156T priority patent/TR200201156T2/xx
Priority to US08/872,023 priority patent/US5874447A/en
Priority to AT97926276T priority patent/ATE200781T1/de
Priority to DK97926276T priority patent/DK0994872T3/da
Priority to BR9714787-7A priority patent/BR9714787A/pt
Priority to AU31080/97A priority patent/AU3108097A/en
Priority to SK1619-99A priority patent/SK283394B6/sk
Priority to CA002293247A priority patent/CA2293247C/en
Priority to EP00203910A priority patent/EP1078925A1/en
Priority to UA99126690A priority patent/UA53707C2/uk
Priority to US09/200,743 priority patent/US7598271B1/en
Publication of WO1998056787A1 publication Critical patent/WO1998056787A1/en
Priority to NO19995455A priority patent/NO317371B1/no
Priority to IS5249A priority patent/IS1927B/is
Priority to BG103980A priority patent/BG64315B1/bg
Priority to HK00106418A priority patent/HK1027352A1/xx
Priority to GR20010400220T priority patent/GR3035784T3/el
Priority to US09/855,710 priority patent/US6900327B2/en
Priority to NO20033765A priority patent/NO20033765D0/no
Priority to NO20033766A priority patent/NO20033766D0/no
Priority to IS7098A priority patent/IS7098A/is
Priority to US12/358,997 priority patent/US20090326233A1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • 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
    • 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

Definitions

  • the present invention relates to a group of tri-substituted, 4-phenylpiperidines, to a process for preparing such compounds, to a medicament comprising such compounds, and to the use of such compounds for the manufacture of a medicament .
  • Paroxetine has been used as a therapeutic agent in the form of a salt with pharmaceutically acceptable acids.
  • the first clinical trials were conducted with the acetate salt.
  • paroxetine hydrochloride A known useful salt of paroxetine is the hydrochloride . This salt is considered to be the active substance in several marketed pharmaceutical products, e.g. Paxil or Seroxat . A number of forms of paroxetine hydrochloride have been described:
  • EP 223403 discloses paroxetine hydrochloride hemihydrate and pharmaceutical compositions based thereon. Most of these known salts of paroxetine have unsuitable physico-chemical characteristics for ensuring safe and efficient handling during production thereof and formulation into final forms, since they are unstable (acetate, maleate) and possess undesirable hygroscopi- city.
  • crystalline paroxetine hydrochloride hemihydrate approaches these problems, but as stated in WO 95/16448, its limited photostability causes undesired colouration during classical wet tabletting procedure. Moreover, crystalline paroxetine hydrochloride hemihydrate exhibits only limited solubility in water.
  • the aqueous solubility is low, for example less than 3 g/ml , the dissolution rate at in vivo administration could be rate-limiting in the absorption process.
  • the aqueous solubility of the paroxetine hemihydrate at room temperature exceeds this threshold by a relatively small margin.
  • an object of the present invention is to provide a compound with improved characteristics.
  • the present invention comprises a compound, and pharmaceutically acceptable salts, having the formula I:
  • - R represents an alkyl or alkynyl group having 1-4 carbon atoms, or a phenyl group optionally substituted by C alkyl, alkylthio, alkoxy, halogen, nitro, acylamino, methylsulfonyl or methylenedioxy, or represents tetrahydronaphthyl
  • - R 1 represents hydrogen, trifluoro (C ) alkyl, alkyl or alkynyl ,
  • - X represents hydrogen, alkyl having 1-4 carbon atoms, alkoxy, trifluoroalkyl, hydroxy, halogen, methylthio or aralkoxy, - R 2 represents:
  • phenyl group optionally substituted by one or more of the following groups :
  • the inventors have found that these compounds exhibit good stability and very high solubility. This yields the advantage that high concentrations of the compound are obtainable in small volumes.
  • the R group is preferably the 3,4 methylenedioxyphenyl group of the formula:
  • the X group is preferably a fluorine group attached to position 4 in the phenyl ring.
  • the R 2 group preferably represents a C1-C4 alkyl group, and most preferably represents a C1-C2 alkyl group in order to provide an optimum solubility.
  • the compounds can have a solubility at about 20 °C of at least about 10 mg/ml water, preferably having a solubility in water of at least 100, for example 500 and most preferably of at least 1000 mg/ml water.
  • a process for preparing a compound as above comprising the steps of mixing together a 4 phenylpiperidine compound, a salt and/or a base thereof having the formula II:
  • - R represents an alkyl or alkynyl group having 1-4 carbon atoms, or a phenyl group optionally substituted by C alkyl, alkylthio, alkoxy, halogen, nitro, acylamino, methylsulfonyl or methylenedioxy, or represents tetrahydronaphthyl ,
  • - R represents hydrogen, trifluoro (C ⁇ _. ) alkyl, alkyl or alkynyl
  • - X represents hydrogen, alkyl having 1-4 carbon atoms, alkoxy, trifluoroalkyl, hydroxy, halogen, methylthio or aralkoxy, . with a sulfonic acid of the general formula R_-S0 3 H, wherein R 2 represents: - a C1-C10 alkyl group,
  • phenyl group optionally substituted by one or more of the following groups:
  • the compounds of the invention can be prepared from the free base of the 4 phenylpiperidine, having the formula II, this preferably being paroxetine, by treatment with a sulfonic acid as defined above in a suitable solvent to form a solution of the desired acid addition salt, whereafter this is precipitated out of the solution.
  • the forming of a solution may preferably ' proceed at temperatures from about 0 °C to the boiling point of the solvent .
  • the solution may be purif ied by treatment of activated charcoal , silica gel , kieselguhr or other suitable materials .
  • the solution of a salt of the invention can be formed by dissolution of a salt of 4 phenyl piperidine having the formula II with an organic sulfonic acid .
  • the compounds of the invention may be prepared from a paroxetine C1 -C5 carboxylate , such as the acetate , by addition of corresponding organic sulfonic acid to the solution of the said carboxylate , as follows :
  • a medicament for use as a medicament and, according to a fifth aspect, a medicament comprising this compound, and to the use thereof for treating depressions, obsessive compulsive disorders, panic disorders, bulimia, anorexia, pain, obesity, senile demential, migraine, anorexia, social phobia, depressions arising from pre-menstrual tension.
  • a compound of the invention as a reagent in further syntheses. More specifically, the compounds of the present invention can be used as a start reagent for forming further acid addition salts, for example for providing further paroxetine acid addition salts, by reacting with a suitable reagent, i.e. with a corresponding acid.
  • a suitable reagent i.e. with a corresponding acid.
  • paroxetine acetate proceeds as follows :
  • the preparation of a further salt, as above, results in this further salt having a high purity.
  • the inventors have shown that such salts have a surprisingly high purity.
  • the compounds of the present invention can react with a base, such as an inorganic and/or an organic base, to form (liberate) free bases of the corresponding compounds.
  • a base such as an inorganic and/or an organic base
  • the free bases liberated from the compounds of the present invention have surprisingly higher purity than if prepared by known methods which is especially important in case of their use for production of pharmaceuticals .
  • the new compounds of the first aspect of the invention can also form hydrates and/or solvates by a contact with a corresponding reaction partner, i ⁇ e. with water and/or with a solvent.
  • a corresponding reaction partner i ⁇ e. with water and/or with a solvent.
  • further salts, hydrates and solvates for example these of paroxetine, are the: hydrochloride oxalate dihydrate hydrobromide succinate trihydrate hydroiodide tartrate hexahydrate acetate citrate methanolate propionate embonate ethanolate maleate hemihydrate fumarate hydrate
  • the inventors have shown that such salts have a surprisingly high purity.
  • bases which can be employed in the preparation of the free bases are: sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonium hydroxide, sodium carbonate, methylamine, dimethylamine, triethylamine, pyridine and such like.
  • the compounds according to the present invention exhibit high solubility, they can be dosed, for example injected, in a high concentration, low volume solution, this method of dosing being particularly advantageous with certain patients, such as manic depressives and such like, i.e. patients who are unable or unwilling to swallow medicine.
  • compositions according to the present invention comprise a compound of the invention alone or together with a pharmaceutically acceptable carrier or diluent.
  • the preferred formulations are those for oral administration (tablets, capsules) but formulations for parenteral or topical administration are also within the scope of the invention.
  • the high water solubility of the compounds of the invention enables high dissolution rates in solid dosage forms based on the compounds of the invention to be obtained, during the in vitro release as well as good bioavailability after peroral application jLn vivo.
  • the tablets containing compounds of the present invention can be prepared both by tabletting procedure in which water is present (e.g. aqueous granulation) as well as by tabletting processing it which water is absent (direct compression, dry granulation) and may be coated by any suitable means of coating.
  • a seeding crystal of paroxetine methane sulfonate was made as follows:
  • Paroxetine p-toluene sulfonate from paroxetine 5.0 g (15 mmol) of paroxetine was dissolved in 25 ml of hot ethylacetate.
  • Paroxetine p-chlorobenzene sulfonate from paroxetine 1.1 g (3.3 mmol) of paroxetine was dissolved in 3 ml of hot ethylacetate.
  • Paroxetine acetate from paroxetine methane sulfonate 1.0 g (2.4 mmol) of paroxetine methane sulfonate in 5 ml of hot iso-propanol. To this solution was added 0.2 g (3.2 mmol) of acetic acid. The mixture was 0 placed at 4 °C overnight after which a solid was precipitated. The solid was filtered off and washed 3 times with 10 ml of ether and dried in a vacuumoven. 0.5 g (1.3 mmol) off white crystals were obtained 5 Yield 54%
  • the purity of the compound obtained was 99.5% (HPLC) .
  • the compounds of the invention are crystalline, with defined melting points, DSC curves and IR spectra. It cannot be excluded that, under different conditions of their formation and under specific conditions, they could exist also in other crystalline or polymorph modifications which may differ from those as described herein.
  • the compounds of the invention are also generally very stable and non-hygroscopic.
  • the present invention comprising acid addition salts with organic sulfonic acids are substantially free of the bound organic solvent.
  • the amount of bound organic solvent should be less than 2.0% (w/w) as calculated on the anhydrous basis. They nevertheless may contain crystallization water and also unbound water, that is to say water which is other than water of crystallization.
  • Table 2 and 3 examples of results of . hygroscopicity tests and stability tests ( in comparison with known salts of paroxetine) are presented.
  • paroxetine maleate m.p.: 128-130°C.
  • paroxetine acetate m.p.: 123-125°C.
  • H 3 , IH 2.50-3.00 (m, H 4 , H 2a ⁇ , H 6a ⁇ , 3H); 3.05-3.75 (m, H 2 H 6 H 7 , 3H);

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Pain & Pain Management (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Psychiatry (AREA)
  • Child & Adolescent Psychology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
PCT/NL1997/000328 1997-06-10 1997-06-10 4-Phenylpiperidine compounds WO1998056787A1 (en)

Priority Applications (37)

Application Number Priority Date Filing Date Title
AT97926276T ATE200781T1 (de) 1997-06-10 1997-06-10 4-phenylpiperidin-derivate
EP00203910A EP1078925A1 (en) 1997-06-10 1997-06-10 4-Phenylpiperidine compounds
PCT/NL1997/000328 WO1998056787A1 (en) 1997-06-10 1997-06-10 4-Phenylpiperidine compounds
DE29724281U DE29724281U1 (de) 1997-06-10 1997-06-10 4-Phenylpiperidin-Verbindungen
PT97926276T PT994872E (pt) 1997-06-10 1997-06-10 Composto de 4-fenilpiperidina
DE69704679T DE69704679T2 (de) 1997-06-10 1997-06-10 4-phenylpiperidin-derivate
EEP199900570A EE03970B1 (et) 1997-06-10 1997-06-10 4-fenüülpiperidiinühend, selle valmistamine ja kasutamine ning seda sisaldav ravim
SI9730138T SI0994872T1 (is) 1997-06-10 1997-06-10
IL13336697A IL133366A (en) 1997-06-10 1997-06-10 4-Phenylpiperidine compounds, process for their preparation and uses thereof
CZ19994295A CZ295301B6 (cs) 1997-06-10 1997-06-10 Deriváty 4-fenylpiperidinu, způsob jejich přípravy, jejich použití a lék je obsahující
ES97926276T ES2155995T3 (es) 1997-06-10 1997-06-10 Compuestos de 4-fenilpiperidina.
KR1019997011625A KR100543614B1 (ko) 1997-06-10 1997-06-10 4-페닐피페리딘 화합물
JP50212699A JP2002503248A (ja) 1997-06-10 1997-06-10 ４−フェニルピペリジン化合物
DK97926276T DK0994872T3 (da) 1997-06-10 1997-06-10 4-phenylpiperidin-forbindelser
EEP200200633A EE200200633A (et) 1997-06-10 1997-06-10 Meetod triasendatud 4-fenüülpiperidiinühendi soola ja aluse vormide saamiseks, saadud soola ja aluse vormid
PL97336895A PL188450B1 (pl) 1997-06-10 1997-06-10 Pochodne 4-fenylopiperydyny, sposób wytwarzania pochodnych 4-fenylopiperydyny, zastosowanie pochodnej 4-fenylopiperydyny oraz środek farmaceutyczny
HU0003141A HUP0003141A3 (en) 1997-06-10 1997-06-10 4-phenylpiperidine derivatives, process for producing them and pharmaceutical compositions containing them
TR2002/01156T TR200201156T2 (tr) 1997-06-10 1997-06-10 4-Fenilpiperidin bileşimleri.
US08/872,023 US5874447A (en) 1997-06-10 1997-06-10 4-Phenylpiperidine compounds for treating depression
EP97926276A EP0994872B9 (en) 1997-06-10 1997-06-10 4-phenylpiperidine compounds
TR1999/03025T TR199903025T2 (xx) 1997-06-10 1997-06-10 4-Fenilpiperidin bile�imleri.
BR9714787-7A BR9714787A (pt) 1997-06-10 1997-06-10 Compostos de 4- fenilpiperidina e processo para sua preparação
AU31080/97A AU3108097A (en) 1997-06-10 1997-06-10 4-phenylpiperidine compounds
SK1619-99A SK283394B6 (sk) 1997-06-10 1997-06-10 Zlúčeniny 4-fenylpiperidínu a jej farmaceuticky prijateľné soli, spôsob ich prípravy, liečivo s ich obsahom a ich použitie
CA002293247A CA2293247C (en) 1997-06-10 1997-06-10 4-phenylpiperidine compounds
UA99126690A UA53707C2 (uk) 1997-06-10 1997-10-06 Похідні 4-фенілпіперидину, спосіб їх отримання (варіанти) і фармацевтична композиція
US09/200,743 US7598271B1 (en) 1997-06-10 1998-11-30 Crystalline paroxetine methane sulfonate
NO19995455A NO317371B1 (no) 1997-06-10 1999-11-08 4-Fenylpiperidinforbindelser
IS5249A IS1927B (is) 1997-06-10 1999-11-16 4-fenýlpíperidín efnasambönd
BG103980A BG64315B1 (bg) 1997-06-10 1999-12-10 4-фенилпиперидинови соли, метод за получаването им и използването им като лекарствено средство
HK00106418A HK1027352A1 (en) 1997-06-10 2000-10-10 4-phenylpiperidine compounds
GR20010400220T GR3035784T3 (en) 1997-06-10 2001-04-26 4-phenylpiperidine compounds
US09/855,710 US6900327B2 (en) 1997-06-10 2001-05-16 4-phenylpiperidine compounds
NO20033766A NO20033766D0 (no) 1997-06-10 2003-08-25 4-Fenylpiperidinforbindelser
NO20033765A NO20033765D0 (no) 1997-06-10 2003-08-25 4-Fenylpiperidinforbindelser
IS7098A IS7098A (is) 1997-06-10 2004-01-08 4-fenýlpíperidín efnasambönd
US12/358,997 US20090326233A1 (en) 1997-06-10 2009-01-23 4-phenylpiperidine compounds

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
PCT/NL1997/000328 WO1998056787A1 (en) 1997-06-10 1997-06-10 4-Phenylpiperidine compounds
US08/872,023 US5874447A (en) 1997-06-10 1997-06-10 4-Phenylpiperidine compounds for treating depression

Publications (1)

Publication Number Publication Date
WO1998056787A1 true WO1998056787A1 (en) 1998-12-17

Family

ID=26647319

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/NL1997/000328 WO1998056787A1 (en) 1997-06-10 1997-06-10 4-Phenylpiperidine compounds

Country Status (26)

Country Link
US (4) US5874447A (is)
EP (2) EP0994872B9 (is)
JP (1) JP2002503248A (is)
KR (1) KR100543614B1 (is)
AT (1) ATE200781T1 (is)
AU (1) AU3108097A (is)
BG (1) BG64315B1 (is)
BR (1) BR9714787A (is)
CA (1) CA2293247C (is)
CZ (1) CZ295301B6 (is)
DE (2) DE69704679T2 (is)
DK (1) DK0994872T3 (is)
EE (2) EE03970B1 (is)
ES (1) ES2155995T3 (is)
GR (1) GR3035784T3 (is)
HK (1) HK1027352A1 (is)
HU (1) HUP0003141A3 (is)
IL (1) IL133366A (is)
IS (2) IS1927B (is)
NO (3) NO317371B1 (is)
PL (1) PL188450B1 (is)
PT (1) PT994872E (is)
SI (1) SI0994872T1 (is)
SK (1) SK283394B6 (is)
TR (2) TR199903025T2 (is)
WO (1) WO1998056787A1 (is)

Cited By (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2336364A (en) * 1998-07-02 1999-10-20 Smithkline Beecham Plc Paroxetine methanesulfonate
WO1999052901A1 (en) * 1998-04-09 1999-10-21 Smithkline Beecham Plc Paroxetine maleate
WO2000001692A1 (en) * 1998-07-02 2000-01-13 Smithkline Beecham Plc Salts of paroxetine
WO2000008016A1 (en) * 1998-08-08 2000-02-17 Smithkline Beecham Plc Paroxetine salts
WO2000035910A1 (en) * 1998-12-11 2000-06-22 Smithkline Beecham Plc Derivative of paroxetine
WO2000039121A1 (en) * 1998-12-29 2000-07-06 Smithkline Beecham P.L.C. Process for the preparation of an acetate salt of paroxetine or paroxetine analogues
WO2000039122A1 (en) * 1998-12-29 2000-07-06 Smithkline Beecham Plc Process for the preparation of an acetate salt of paroxetine or paroxetine analogues
WO2000039123A1 (en) * 1998-12-29 2000-07-06 Smithkline Beecham Plc Process for the preparation of an acetate salt of paroxetine or paroxetine analogues
GR1003490B (el) * 1999-06-22 2000-11-30 Smithkline Beecham P.L.C. Νεες φαρμακευτικες συνθεσεις που περιεχουν αλας παροξετινης
WO2000078752A1 (en) * 1999-06-22 2000-12-28 Smithkline Beecham P.L.C. Process for the production of paroxetine hydrochloride
WO2000078290A2 (en) * 1999-06-22 2000-12-28 Smithkline Beecham P.L.C. Pharmaceutical composition comprising a salt of paroxetine
WO2001012624A1 (en) * 1999-08-12 2001-02-22 Smithkline Beecham P.L.C. Paroxetine
WO2002017921A2 (en) * 2000-08-28 2002-03-07 Synthon B.V. Paroxetine compositions and processes for making the same
WO2002022609A1 (fr) * 2000-09-14 2002-03-21 Asahi Glass Company, Limited Procede de production de sel de paroxetine sensiblement exempt de solvant organique
WO2003020717A1 (en) * 2001-08-02 2003-03-13 Spurcourt Limited Paroxetine isethionate salt, process of preparation and use in the treatment of depression
WO2003082804A1 (en) * 2002-03-28 2003-10-09 Synthon B.V. Venlafaxine besylate
US8501777B2 (en) 2005-10-13 2013-08-06 Nsab, Filial Af Neurosearch Sweden Ab, Sverige 3,5-disubstituted phenyl-piperidines as modulators of dopamine neurotransmission
WO2013115163A1 (ja) * 2012-01-31 2013-08-08 エーザイ・アール・アンド・ディー・マネジメント株式会社 パロキセチン誘導体
USRE46117E1 (en) 1999-12-22 2016-08-23 Teva Pharmaceuticals International Gmbh Modulators of dopamine neurotransmission
US9925174B2 (en) 2002-03-07 2018-03-27 Boehringer Ingelheim International Gmbh Administration form for the oral application of 3-[(2-{[4-(hexyloxycarbonyl-amino-imino-methyl)-phenylamino]-methyl}-1-methyl-1 H-benzimidazol acid ethyl ester and the salts thereof
US10259791B2 (en) 2014-08-28 2019-04-16 Eisai R&D Management Co., Ltd. High-purity quinoline derivative and method for manufacturing same
US11090386B2 (en) 2015-02-25 2021-08-17 Eisai R&D Management Co., Ltd. Method for suppressing bitterness of quinoline derivative
US11207308B2 (en) 2012-04-04 2021-12-28 Prilenia Neurotherapeutics Ltd. Pharmaceutical compositions for combination therapy
US11369623B2 (en) 2015-06-16 2022-06-28 Prism Pharma Co., Ltd. Anticancer combination of a CBP/catenin inhibitor and an immune checkpoint inhibitor
US11598776B2 (en) 2011-06-03 2023-03-07 Eisai R&D Management Co., Ltd. Biomarkers for predicting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HU221921B1 (hu) * 1996-07-08 2003-02-28 Richter Gedeon Vegyészeti Gyár Rt. N-benzil-piperidin- és tetrahidropiridinszármazékok és eljárás azok előállítására
US20010023252A1 (en) * 1998-07-02 2001-09-20 Smithkline Beecham Plc Novel compound
AU724845B3 (en) * 1998-07-02 2000-09-28 Smithkline Beecham Plc Novel compound
DK1109806T3 (da) * 1999-07-01 2003-12-22 Italfarmaco Spa Komplekser af paroxetin med cyclodextriner eller cyclodextrinderivater
US6503927B1 (en) * 1999-10-28 2003-01-07 Pentech Pharmaceuticals, Inc. Amorphous paroxetine composition
CZ20023694A3 (cs) * 2000-05-12 2003-05-14 Synthon B. V. Tosylátové soli 4-(p-fluorfenyl)-piperidin-3-methanolů
ES2209876T3 (es) * 2000-05-12 2004-07-01 Synthon B.V. Compuestos de piperidina y procedimiento para su preparacion.
DE20100529U1 (de) * 2001-01-11 2001-05-10 Synthon Bv Pharmazeutische Tablette umfassend Paroxetinmesylat
US6720003B2 (en) 2001-02-16 2004-04-13 Andrx Corporation Serotonin reuptake inhibitor formulations
NL1017421C2 (nl) * 2001-02-21 2002-01-15 Synthon Bv Werkwijze voor het vervaardigen van paroxetine.
WO2002085360A1 (en) * 2001-04-25 2002-10-31 Pentech Pharmaceuticals, Inc. Optimized procedures for the manufacture of paroxetine salts
WO2002100829A2 (en) * 2001-06-13 2002-12-19 Teva Pharmaceutical Industries Ltd. Process for the preparation of paroxetine substantially free of alkoxy impurities
IL159280A0 (en) * 2001-06-14 2004-06-01 Teva Pharma A process for preparing paroxetine hcl which limits formation of pink colored compounds
US20040220153A1 (en) * 2002-09-24 2004-11-04 Jost-Price Edward Roydon Methods and reagents for the treatment of diseases and disorders associated with increased levels of proinflammatory cytokines
US7202259B2 (en) * 2002-11-18 2007-04-10 Euro-Celtique S.A. Therapeutic agents useful for treating pain
CA2548917C (en) 2003-12-11 2014-09-23 Sepracor Inc. Combination of a sedative and a neurotransmitter modulator, and methods for improving sleep quality and treating depression
EP1778183B1 (en) * 2004-08-18 2018-06-27 Synthon B.V. Liquid paroxetine compositions
US20060039975A1 (en) * 2004-08-20 2006-02-23 Zalman Vilkov Paroxetine formulations
JP5301991B2 (ja) * 2005-07-29 2013-09-25 コンサート ファーマシューティカルズ インコーポレイテッド 新規なベンゾ［ｄ］［１，３］−ジオキソール誘導体
US20080033011A1 (en) * 2005-07-29 2008-02-07 Concert Pharmaceuticals Inc. Novel benzo[d][1,3]-dioxol derivatives
AU2006315684A1 (en) * 2005-11-14 2007-05-24 Auspex Pharmaceuticals, Inc. Substituted phenylpiperidines with serotoninergic activity and enhanced therapeutic properties
US20080033050A1 (en) 2006-08-04 2008-02-07 Richards Patricia Allison Tewe Method of treating thermoregulatory disfunction with paroxetine
JP5647519B2 (ja) * 2007-09-13 2014-12-24 コンサート ファーマシューティカルズ インコーポレイテッド 重水素化カテコールおよびベンゾ［ｄ］［１，３］ジオキソールおよびその誘導体の合成
US9138430B2 (en) * 2007-12-27 2015-09-22 Mylan Specialty L.P. Formulation and method for the release of paroxetine in the large intestine

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0152273A2 (en) * 1984-02-07 1985-08-21 A/S Ferrosan A phenylpiperidine derivative, and its salts, their preparation, compositions containing them, and their therapeutic use
EP0190496A2 (en) * 1984-12-13 1986-08-13 Beecham Group Plc Piperidine derivatives having a gastro-intestinal activity
EP0223403A2 (en) * 1985-10-25 1987-05-27 Beecham Group Plc Piperidine derivative, its preparation, and its use as medicament
EP0269303A2 (en) * 1986-11-11 1988-06-01 Novo Nordisk A/S Piperidine derivative for treating pain
WO1996024595A1 (en) * 1995-02-06 1996-08-15 Smithkline Beecham Plc New forms of paroxetin hydrochloride

Family Cites Families (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AT99678B (de) * 1921-09-21 1925-04-10 Hoechst Ag Verfahren zur Darstellung arzneilich wirksamer Quecksilberverbindungen.
GB1422263A (en) 1973-01-30 1976-01-21 Ferrosan As 4-phenyl-piperidine compounds
GB8430581D0 (en) * 1984-12-04 1985-01-09 Ferrosan As Treatment
GB8520154D0 (en) * 1985-08-10 1985-09-18 Beecham Group Plc Chemical process
EP0223334B1 (en) * 1985-08-10 1991-07-10 Beecham Group Plc Process for the preparation of aryl-piperidine carbinols
US5258388A (en) * 1986-03-17 1993-11-02 University Of Florida Anticholinergic compounds, compositions and methods of treatment
IE66332B1 (en) * 1986-11-03 1995-12-27 Novo Nordisk As Piperidine compounds and their preparation and use
GB8714707D0 (en) * 1987-06-23 1987-07-29 Beecham Group Plc Chemical process
DK715988D0 (da) * 1988-12-22 1988-12-22 Ferrosan As Etherifikation og dealkylering af piperidin-derivater samt intermediater
DK716088D0 (da) * 1988-12-22 1988-12-22 Ferrosan As Reduktion af piperidin-dion-derivater samt intermediat
WO1992009281A2 (en) 1990-11-24 1992-06-11 Beecham Group Plc Use of paroxetine for the treatment of senile dementia, bulimia, migraine or anorexia
GB9209687D0 (en) * 1992-05-06 1992-06-17 Smithkline Beecham Plc Novel process
US5258517A (en) * 1992-08-06 1993-11-02 Sepracor, Inc. Method of preparing optically pure precursors of paroxetine
JP2773587B2 (ja) * 1992-11-30 1998-07-09 東レ株式会社 Ｏ，ｏ´−ジアシル酒石酸無水物の製造法
US5276042A (en) 1993-04-16 1994-01-04 Crenshaw Roger T Treatment of premature ejaculation
US5546683A (en) * 1993-09-29 1996-08-20 Clark; George J. Bucket attachment device with remote controlled retractable pins
IT1274241B (it) * 1993-12-03 1997-07-15 Smithkline Beecham Farma Complessi agente terapeutico/matrice polimerica dotati di migliorate caratteristiche di sapore e composizioni farmaceutiche che li contengono
GB9325644D0 (en) 1993-12-15 1994-02-16 Smithkline Beecham Plc Novel formulation
US5668134A (en) * 1994-01-28 1997-09-16 G. D. Searle & Co. Method for preventing or reducing photosensitivity and/or phototoxicity reactions to medications
GB9402029D0 (en) * 1994-02-03 1994-03-30 Smithkline Beecham Plc Novel formulation
CA2143070C (en) * 1994-02-22 2001-12-18 Pankaj Modi Oral controlled release liquid suspension pharmaceutical formulation
EP0714663A3 (en) * 1994-11-28 1997-01-15 Lilly Co Eli Potentiation of drug responses by serotonin 1A receptor antagonists
JPH08220486A (ja) * 1994-12-14 1996-08-30 Kato Kogei:Kk 眼鏡フレーム
GB2297550C2 (en) * 1995-02-06 1997-04-09 Smithkline Beecham Plc Paroxetine hydrochloride anhydrate substantially free of bound organic solvent
US5856493A (en) * 1995-02-06 1999-01-05 Smithkline Beecham Corporation Process for making novel form of paroxeting hydrochloride anhydrate
EP0818990A1 (en) * 1995-04-03 1998-01-21 Abbott Laboratories Homogeneous mixtures of low temperature-melting drugs and additives for controlled release
NZ307479A (en) * 1995-05-17 1999-08-30 Novo Nordisk As A process for preparing 4-(4-halo substituted phenyl)-3-(3,4-methylenedioxy phenoxy methyl)piperidine derivatives
JP2813768B2 (ja) * 1995-05-24 1998-10-22 農林水産省家畜衛生試験場長 口蹄疫診断用ペプチドおよび当該ペプチドを含有する口蹄疫診断用抗原
GB9514842D0 (en) * 1995-07-20 1995-09-20 Smithkline Beecham Plc Novel formulation
CA2234640A1 (en) * 1995-10-31 1997-05-09 Merck & Co., Inc. Process for preparing substituted azetidinones
IT1276160B1 (it) * 1995-11-22 1997-10-27 Recordati Chem Pharm Composizioni farmaceutiche orali a pronto rilascio per sospensioni estemporanee
GB9526645D0 (en) * 1995-12-28 1996-02-28 Chiroscience Ltd Stereoselective synthesis
ES2117557B1 (es) * 1996-02-29 1999-07-01 Ferrer Int Nuevo procedimiento de obtencion de (-)-trans -n-p-fluorobenzoilmetil-4-(p-fluorofenil)-3- ((3,4-(metilendioxi)fenoxi ) metil)-piperidina.
JP3446468B2 (ja) * 1996-04-15 2003-09-16 旭硝子株式会社 ピペリジンカルビノール類の製造方法
CA2206592A1 (en) * 1996-05-30 1997-11-30 Shu-Zhong Wang Method of producing amorphous paroxetine hydrochloride
JP3882224B2 (ja) * 1996-05-31 2007-02-14 旭硝子株式会社 パロキセチンの製造方法
EP1384711A1 (en) * 1996-06-13 2004-01-28 SUMIKA FINE CHEMICALS Co., Ltd. Optical resolution of a piperidine derivative
HU221921B1 (hu) * 1996-07-08 2003-02-28 Richter Gedeon Vegyészeti Gyár Rt. N-benzil-piperidin- és tetrahidropiridinszármazékok és eljárás azok előállítására
US5672609A (en) * 1996-07-18 1997-09-30 Eli Lilly And Company Pyridine compounds, intermediates compositions and methods of use
CA2187128A1 (en) * 1996-10-04 1997-06-26 K. S. Keshava Murthy New and useful polymorph of anhydrous paroxetine hydrochloride
US5955475A (en) * 1997-06-30 1999-09-21 Endo Pharmaceuticals Inc. Process for manufacturing paroxetine solid dispersions
CH689805A8 (fr) * 1998-07-02 2000-02-29 Smithkline Beecham Plc Méthanesulfonate de paroxétine, procédé pour sa préparation et compositions pharmaceutiques le contenant.

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0152273A2 (en) * 1984-02-07 1985-08-21 A/S Ferrosan A phenylpiperidine derivative, and its salts, their preparation, compositions containing them, and their therapeutic use
EP0190496A2 (en) * 1984-12-13 1986-08-13 Beecham Group Plc Piperidine derivatives having a gastro-intestinal activity
EP0223403A2 (en) * 1985-10-25 1987-05-27 Beecham Group Plc Piperidine derivative, its preparation, and its use as medicament
EP0269303A2 (en) * 1986-11-11 1988-06-01 Novo Nordisk A/S Piperidine derivative for treating pain
WO1996024595A1 (en) * 1995-02-06 1996-08-15 Smithkline Beecham Plc New forms of paroxetin hydrochloride

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BUXTON P C ET AL: "Solid-state forms of paroxetine hydrochloride", INT. J. PHARM. (IJPHDE,03785173);88; VOL.42 (1-3); PP.135-43, BEECHAM PHARM.;BIOSCI. RES. CENT.; EPSOM SURREY; KT18 5XQ; UK (GB), XP000572028 *

Cited By (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999052901A1 (en) * 1998-04-09 1999-10-21 Smithkline Beecham Plc Paroxetine maleate
GB2336364B (en) * 1998-07-02 2000-05-10 Smithkline Beecham Plc Paroxetine salt
EP0970955A1 (en) * 1998-07-02 2000-01-12 Smithkline Beecham Plc Paroxetine methanesulfonate
GB2352395B (en) * 1998-07-02 2004-02-11 Smithkline Beecham Plc Paroxetine methanesulfonate
WO2000001692A1 (en) * 1998-07-02 2000-01-13 Smithkline Beecham Plc Salts of paroxetine
WO2000001694A1 (en) * 1998-07-02 2000-01-13 Smithkline Beecham Plc Paroxetine methanesulfonate
AT3185U3 (de) * 1998-07-02 2000-01-25 Smithkline Beecham Plc Paroxetinmethansulfonat
GB2339428A (en) * 1998-07-02 2000-01-26 Smithkline Beecham Plc Paroxetine methanesulfonate
ES2158778A1 (es) * 1998-07-02 2001-09-01 Smithkline Beecham Plc Compuestos de sales de paroxetina, su preparacion y uso, y composiciones farmaceuticas que los contienen.
GB2336364A (en) * 1998-07-02 1999-10-20 Smithkline Beecham Plc Paroxetine methanesulfonate
GB2352395A (en) * 1998-07-02 2001-01-31 Smithkline Beecham Plc Paroxetine methanesulfonate
FR2802098A1 (fr) * 1998-07-02 2001-06-15 Smithkline Beecham Plc Compositions pharmaceutiques comprenant un sel de paroxetine
FR2780728A1 (fr) * 1998-07-02 2000-01-07 Smithkline Beecham Plc Sel de paroxetine nouveau, procede pour sa preparation et compositions pharmaceutiques le contenant
GR990100140A (el) * 1998-07-02 2000-03-31 Smithkline Beecham P.L.C. Νεες ενωσεις
EP1288214A1 (en) * 1998-07-02 2003-03-05 Smithkline Beecham Plc Paroxetine methanesulfonate
EP1020463A1 (en) * 1998-07-02 2000-07-19 Smithkline Beecham Plc Paroxetine methanesulfonate
EP1020464A1 (en) * 1998-07-02 2000-07-19 Smithkline Beecham Plc Paroxetine methansulfonate
BE1012403A5 (fr) * 1998-07-02 2000-10-03 Smithkline Beecham Plc Sel de paroxetine nouveau, procede pour sa preparation et compositions pharmaceutiques le contenant.
GB2377637A (en) * 1998-07-02 2003-01-22 Smithkline Beecham Plc Paroxetine methanesulphonate composition
JP2002519422A (ja) * 1998-07-02 2002-07-02 スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー パロキセチンメタンスルホネート
GB2367003A (en) * 1998-07-02 2002-03-27 Smithkline Beecham Plc Paroxetine methansulphonate compositions
WO2000008016A1 (en) * 1998-08-08 2000-02-17 Smithkline Beecham Plc Paroxetine salts
WO2000035910A1 (en) * 1998-12-11 2000-06-22 Smithkline Beecham Plc Derivative of paroxetine
WO2000039122A1 (en) * 1998-12-29 2000-07-06 Smithkline Beecham Plc Process for the preparation of an acetate salt of paroxetine or paroxetine analogues
WO2000039123A1 (en) * 1998-12-29 2000-07-06 Smithkline Beecham Plc Process for the preparation of an acetate salt of paroxetine or paroxetine analogues
WO2000039121A1 (en) * 1998-12-29 2000-07-06 Smithkline Beecham P.L.C. Process for the preparation of an acetate salt of paroxetine or paroxetine analogues
GR1003490B (el) * 1999-06-22 2000-11-30 Smithkline Beecham P.L.C. Νεες φαρμακευτικες συνθεσεις που περιεχουν αλας παροξετινης
FR2795327A1 (fr) * 1999-06-22 2000-12-29 Smithkline Beecham Plc Compositions pharmaceutiques nouvellles de methanesulfonate de paroxetine
WO2000078290A3 (en) * 1999-06-22 2001-05-25 Smithkline Beecham Plc Pharmaceutical composition comprising a salt of paroxetine
WO2000078291A1 (en) * 1999-06-22 2000-12-28 Smithkline Beecham P.L.C. Composition of paroxetine methanesulfonate
WO2000078290A2 (en) * 1999-06-22 2000-12-28 Smithkline Beecham P.L.C. Pharmaceutical composition comprising a salt of paroxetine
ES2159260A1 (es) * 1999-06-22 2001-09-16 Smithkline Beechan Plc Nueva composicion de metanosulfonato de paroxetina
BE1012806A3 (fr) * 1999-06-22 2001-03-06 Smithkline Beecham Plc Compositions nouvelles de methanesulfonate de paroxetine.
WO2000078752A1 (en) * 1999-06-22 2000-12-28 Smithkline Beecham P.L.C. Process for the production of paroxetine hydrochloride
GB2351233A (en) * 1999-06-22 2000-12-27 Smithkline Beecham Plc Compositions comprising paroxetine methanesulfonate
NL1013749C2 (nl) * 1999-06-22 2001-01-08 Smithkline Beecham Plc Nieuwe samenstelling.
EP1064936A1 (en) * 1999-06-22 2001-01-03 Smithkline Beecham Plc Novel composition of paroxetine methanesulfonate
WO2001012624A1 (en) * 1999-08-12 2001-02-22 Smithkline Beecham P.L.C. Paroxetine
USRE46117E1 (en) 1999-12-22 2016-08-23 Teva Pharmaceuticals International Gmbh Modulators of dopamine neurotransmission
WO2002017921A3 (en) * 2000-08-28 2002-10-03 Synthon Bv Paroxetine compositions and processes for making the same
WO2002017921A2 (en) * 2000-08-28 2002-03-07 Synthon B.V. Paroxetine compositions and processes for making the same
WO2002022609A1 (fr) * 2000-09-14 2002-03-21 Asahi Glass Company, Limited Procede de production de sel de paroxetine sensiblement exempt de solvant organique
WO2003020717A1 (en) * 2001-08-02 2003-03-13 Spurcourt Limited Paroxetine isethionate salt, process of preparation and use in the treatment of depression
US9925174B2 (en) 2002-03-07 2018-03-27 Boehringer Ingelheim International Gmbh Administration form for the oral application of 3-[(2-{[4-(hexyloxycarbonyl-amino-imino-methyl)-phenylamino]-methyl}-1-methyl-1 H-benzimidazol acid ethyl ester and the salts thereof
WO2003082804A1 (en) * 2002-03-28 2003-10-09 Synthon B.V. Venlafaxine besylate
US8501777B2 (en) 2005-10-13 2013-08-06 Nsab, Filial Af Neurosearch Sweden Ab, Sverige 3,5-disubstituted phenyl-piperidines as modulators of dopamine neurotransmission
US11598776B2 (en) 2011-06-03 2023-03-07 Eisai R&D Management Co., Ltd. Biomarkers for predicting and assessing responsiveness of thyroid and kidney cancer subjects to lenvatinib compounds
RU2616610C2 (ru) * 2012-01-31 2017-04-18 Эйсай Ар Энд Ди Менеджмент Ко., Лтд. Производное пароксетина
US8933100B2 (en) 2012-01-31 2015-01-13 Eisai R&D Management Co., Ltd. Paroxetine derivative
CN104039777A (zh) * 2012-01-31 2014-09-10 卫材R&D管理有限公司 帕罗西汀衍生物
WO2013115163A1 (ja) * 2012-01-31 2013-08-08 エーザイ・アール・アンド・ディー・マネジメント株式会社 パロキセチン誘導体
US11207308B2 (en) 2012-04-04 2021-12-28 Prilenia Neurotherapeutics Ltd. Pharmaceutical compositions for combination therapy
US10259791B2 (en) 2014-08-28 2019-04-16 Eisai R&D Management Co., Ltd. High-purity quinoline derivative and method for manufacturing same
US11090386B2 (en) 2015-02-25 2021-08-17 Eisai R&D Management Co., Ltd. Method for suppressing bitterness of quinoline derivative
US11369623B2 (en) 2015-06-16 2022-06-28 Prism Pharma Co., Ltd. Anticancer combination of a CBP/catenin inhibitor and an immune checkpoint inhibitor

Also Published As

Publication number Publication date
NO20033765L (no) 2000-02-09
IS7098A (is) 2004-01-08
IS1927B (is) 2004-04-15
NO20033766L (no) 2000-02-09
BR9714787A (pt) 2000-07-18
KR100543614B1 (ko) 2006-01-20
BG103980A (en) 2000-07-31
EE9900570A (et) 2000-08-15
DE69704679D1 (de) 2001-05-31
CA2293247C (en) 2005-04-12
NO20033766D0 (no) 2003-08-25
US5874447A (en) 1999-02-23
AU3108097A (en) 1998-12-30
HUP0003141A3 (en) 2001-04-28
PL336895A1 (en) 2000-07-17
GR3035784T3 (en) 2001-07-31
US20010031767A1 (en) 2001-10-18
BG64315B1 (bg) 2004-09-30
NO995455L (no) 2000-02-09
DE69704679T2 (de) 2001-09-13
ES2155995T3 (es) 2001-06-01
US20090326233A1 (en) 2009-12-31
JP2002503248A (ja) 2002-01-29
SI0994872T1 (is) 2001-08-31
IL133366A0 (en) 2001-04-30
CA2293247A1 (en) 1998-12-17
PL188450B1 (pl) 2005-02-28
EE200200633A (et) 2003-02-17
NO995455D0 (no) 1999-11-08
SK161999A3 (en) 2000-08-14
US7598271B1 (en) 2009-10-06
EP0994872A1 (en) 2000-04-26
TR199903025T2 (xx) 2000-07-21
DE29724281U1 (de) 2000-08-10
PT994872E (pt) 2001-09-28
NO317371B1 (no) 2004-10-18
US6900327B2 (en) 2005-05-31
CZ429599A3 (cs) 2000-04-12
TR200201156T2 (tr) 2002-07-22
IS5249A (is) 1999-11-16
CZ295301B6 (cs) 2005-07-13
SK283394B6 (sk) 2003-07-01
EP0994872B1 (en) 2001-04-25
EE03970B1 (et) 2003-02-17
HUP0003141A2 (en) 2001-03-28
DK0994872T3 (da) 2001-05-28
IL133366A (en) 2005-11-20
EP0994872B9 (en) 2001-12-05
KR20010013615A (ko) 2001-02-26
ATE200781T1 (de) 2001-05-15
HK1027352A1 (en) 2001-01-12
EP1078925A1 (en) 2001-02-28
NO20033765D0 (no) 2003-08-25

Similar Documents

Publication Publication Date Title
EP0994872B9 (en) 4-phenylpiperidine compounds
CA1287060C (en) Crystalline paroxetine hcl
JP3022951B2 (ja) アロイル−ピペリジン誘導体
WO1997028141A1 (fr) Nouvelles piperazines aromatiques derivees de cycloazanes substitues, ainsi que leur procede de preparation, les compositions pharmaceutiques et leur utilisation comme medicaments
JP2003517013A (ja) フェノキシプロパノールアミン類、それらの製造方法およびそれらを含む医薬組成物
KR20010006120A (ko) 혈관 수축제로써의 인다졸 아마이드 화합물
CZ289752B6 (cs) 1-Fenylalkanonové ligandy 5-HT4 receptoru, farmaceutický prostředek, který je obsahuje, způsob jejich přípravy a pouľití
EP0106462A2 (en) Dihydropyridines
HU206677B (en) Process for producing new 4,4-disubstituted piperidine derivatives and pharmaceutical compositions containing them
IE912456A1 (en) New heterocyclic chemistry
AU705427B2 (en) Alpha-(substituted alkylphenyl) -4-(hydroxydiphenylmethyl)-1-piperidine butanol derivatives, their preparation and their use as anti-histamines, anti-allergy agents and bronchodilators
FR2549058A1 (fr) Nouveaux derives de la 1,4-dihydropyridine, leur preparation et leur utilisation comme medicaments
JPH0135822B2 (is)
AU2002301956B2 (en) 4-phenylpiperidine compounds
CA2455954A1 (en) 4-phenylpiperidine compounds
MXPA99011355A (en) 4-phenylpiperidine compounds
JPH0588222B2 (is)
DK200000380U1 (da) 4-phenyl-piperidin-forbindelser
WO2001025201A1 (en) Process for the preparation of paroxetin intermediate
WO2001025202A1 (en) Process for the preparation of paroxetine intermediate
UA53707C2 (uk) Похідні 4-фенілпіперидину, спосіб їх отримання (варіанти) і фармацевтична композиція

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 97182237.9

Country of ref document: CN

AK Designated states

Kind code of ref document: A1

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE HU IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK TJ TM TR TT UA UG UZ VN

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH KE LS MW SD SZ UG AM AZ BY KG KZ MD RU TJ TM AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 1997926276

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 161999

Country of ref document: SK

WWE Wipo information: entry into national phase

Ref document number: PV1999-4295

Country of ref document: CZ

WWE Wipo information: entry into national phase

Ref document number: 1999/03025

Country of ref document: TR

WWE Wipo information: entry into national phase

Ref document number: 501604

Country of ref document: NZ

WWE Wipo information: entry into national phase

Ref document number: PA/a/1999/011355

Country of ref document: MX

ENP Entry into the national phase

Ref document number: 2293247

Country of ref document: CA

Ref document number: 2293247

Country of ref document: CA

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 1019997011625

Country of ref document: KR

ENP Entry into the national phase

Ref document number: 1999 502126

Country of ref document: JP

Kind code of ref document: A

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWP Wipo information: published in national office

Ref document number: PV1999-4295

Country of ref document: CZ

WWP Wipo information: published in national office

Ref document number: 1997926276

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1019997011625

Country of ref document: KR

WWG Wipo information: grant in national office

Ref document number: 1997926276

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2002/01156

Country of ref document: TR

WWE Wipo information: entry into national phase

Ref document number: 332003

Country of ref document: SK

ENP Entry into the national phase

Ref document number: 10868597

Country of ref document: BG

Kind code of ref document: A

Ref document number: 10868497

Country of ref document: BG

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 108684

Country of ref document: BG

Ref document number: 108685

Country of ref document: BG

WWE Wipo information: entry into national phase

Ref document number: PV2004-1165

Country of ref document: CZ

WWG Wipo information: grant in national office

Ref document number: PV1999-4295

Country of ref document: CZ

WWG Wipo information: grant in national office

Ref document number: 1019997011625

Country of ref document: KR