WO1992012149A1 - Derives azabicydiques et azatricydiques, leurs procedes et intermediaires de preparation et compositions pharmaceutiques les contenant - Google Patents

Derives azabicydiques et azatricydiques, leurs procedes et intermediaires de preparation et compositions pharmaceutiques les contenant Download PDF

Info

Publication number
WO1992012149A1
WO1992012149A1 PCT/GB1992/000050 GB9200050W WO9212149A1 WO 1992012149 A1 WO1992012149 A1 WO 1992012149A1 GB 9200050 W GB9200050 W GB 9200050W WO 9212149 A1 WO9212149 A1 WO 9212149A1
Authority
WO
WIPO (PCT)
Prior art keywords
hydrogen
alkyl
compound according
formula
alkoxy
Prior art date
Application number
PCT/GB1992/000050
Other languages
English (en)
Inventor
Francis David King
Original Assignee
Smithkline Beecham Plc
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
Priority claimed from GB919100370A external-priority patent/GB9100370D0/en
Priority claimed from GB919100580A external-priority patent/GB9100580D0/en
Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc
Priority to JP4502573A priority Critical patent/JPH06506443A/ja
Publication of WO1992012149A1 publication Critical patent/WO1992012149A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
    • C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems

Definitions

  • This invention relates to novel compounds having useful pharmacological properties, to a process for their
  • EP-A-337547 (Merck Sharp and Dohme Limited), EP-A-329932
  • Patents 4920219 and 4920227 disclose classes of compounds which have a saturated azabicyclic moiety, such as tropanyl, granatyl or quinuclidinyl, and are 5-HT 3 receptor antagonists.
  • X is a phenyl group or a monocyclic 5 or 6 membered
  • heteroaryl group either of which group is optionally fused to a saturated or unsaturated 5-7 membered carbocyclic or heterocyclic ring;
  • A is a linking moiety
  • R is hydrogen or methyl
  • X may be unsubstituted or substituted, usually by one or more substituents selected from halogen, C 1 - 6 alkoxy, C 1-6 alkylthic, C 1- 6 alkyl, hydroxy, amino, C 1-6 alkylamino, C 1 -7 alkanoylamino, or two substituents on X (when fused), may be linked to form a saturated or unsaturated optionally
  • Heteroatoms for heteroaryl and heterocyclic groups are selected from oxygen, nitrogen and sulphur.
  • Halo includes bromo, chloro and fluoro.
  • X may be joined to A by an aromatic carbon atom, or (when X is fused), by a carbocyclic ring carbon atom, or by a heterocyclic ring carbon or nitrogen atom. When X is fused, and A is attached at an aromatic carbon atom, it is
  • Suitable examples of X are as described in the
  • Suitable examples of A include CONH (amide), COO (ester), NHCONH (ureide), CONHCONH (extended ureide), or a group of structure (j):
  • the present invention provides a compound of formula (IA), or a pharmaceutically acceptable salt thereof:
  • Y is NH or O (or is joined to R 10 as defined below);
  • X 1 is a group of formula (a), (b), (c), (d), (e), (f), (g)
  • R a to R e and R g to R h are selected from hydrogen, halogen or hydroxy
  • R 1 is hydrogen and R 2 is hydrogen or C 1 -4 alkyl
  • R 1 and R 2 together are a bond
  • R 3 to R 7 are independently hydrogen or C 1 -6 alkyl
  • R 4 together with R 2 may be C 2-7 polymethylene or C 2 - 6
  • R 8 and R 9 are independently selected from hydrogen or
  • R 11 is hydrogen, halo, C 1-6 alkoxy or C 1-6 alkyl
  • R 10 and R 1 1 are joined to form -OCH (R 15 R 16 )-E- wherein E is
  • R 12 is
  • R 13 is halo, C 1-6 alkyl, C 1-6 alkoxy or C 1-6 alkylthio
  • R 14 is hydrogen or C 1-6 alkyl
  • CO-Y- is in the 1-position and either R 15 is in the
  • R 15 is in the 4-position and is hydrogen, halogen, CF 3 , C 1- 6 alkyl , C 1-7 acyl , C 1- 7 acylamino , phenyl optionally substituted by one or two C 1-6 alkyl, C 1-6 alkoxy or halogen groups, or amino, aminocarbonyl or aminosulphonyl, optionally substituted by one or two C 1-6 alkyl or C 3-8 cycloalkyl groups or by C 4-5 polymethylene or by phenyl, C 1-6 alkylsulphonyl, C 1-6 alkylsulphinyl , C 1- 6 alkoxy, C 1 -6 alkylthio, hydroxy or nitro; or
  • CO-Y- is in the 3-position and either R 15 is in the
  • R 15 is in the 4-position and is hydrogen or C 1-6 alkoxy;
  • L is CH or N
  • moieties in alkyl or alkyl containing groups in Z or in R 1 to R 15 include methyl, ethyl, n- and iso-propyl, n-, iso-, sec- and tert-butyl, preferably methyl.
  • Cycloalkyl moieties include C 3 , C 4 , C 5 , C 6 , C 7 and C 8 cycloalkyl.
  • Halo moieties include fluoro, chloro, bromo and iodo.
  • R 2 and R 4 or R 8 and R 9 when joined include C 2 , C 3 , C 4 , C 5 or C 6 polymethylene, preferably C 2 , C 3 , C 4 or C 5 Polymethylene .
  • R a to R e and R g to R h are preferably selected from hydrogen, fluoro, chloro and hydroxy, most preferably hydrogen.
  • R b may be 5-, 6- or 7-chloro or fluoro.
  • R 1 and R 3 is preferably hydrogen and one or both of R 2 and R 4 (most preferably both) are alkyl groups, such as methyl, or are joined to form C 2-7 polymethylene; or when one of R 2 and R 4 is hydrogen, the other is preferably ethyl or n- or iso- propyl.
  • R 5 is preferably hydrogen or a methyl or ethyl group.
  • R 7 is preferably methyl.
  • R 8 and R 9 are preferably both methyl groups.
  • R 10 is C 1-6 alkoxy or is joined to Y
  • R 12 is preferably amino and R 13 is preferably chloro or bromo, most preferably chloro.
  • R 10 is preferably methoxy when C 1-6 alkoxy.
  • R 11 and R 13 are preferably chloro or methyl and R 10 is preferably hydrogen.
  • R 14 is preferably hydrogen or methyl.
  • R 15 when in the 4-position, include the following: hydrogen, chloro, bromo, methyl, ethyl, amino, methylamino, dimethylamino, phenyl, C 1 _ 4 alkanoylamino such as formylamino, acetylamino, propionylamino, n- and
  • aminosulphonyl optionally substituted by one or two methyl, ethyl, n- or iso-propyl, n-, sec-, iso- or tert-butyl or phenyl groups; nitro, n- and iso-propoxy, methylthio, ethylthio, n- and iso-propylthio, hydroxy, methylsulphonyl and ethylsulphonyl or when R 15 is in the 3-position suitable examples, include the following groups, hydrogen, methyl, ethyl, n- or iso-propyl, methoxy, and ethoxy.
  • R 15 when in the 1-position include hydrogen, methyl, ethyl, n- or iso- propyl, or when R 15 is in the 4-position, suitable examples include the following: hydrogen, methoxy and ethoxy.
  • Preferred R 15 groups, in any of the positions specified above, include hydrogen, methyl and methoxy.
  • CO-Y- is preferably in the 1-position.
  • Y is preferably NH.
  • the pharmaceutically acceptable salts of the compounds of the formula (I) include acid addition salts with
  • Examples of pharmaceutically acceptable salts include quaternary derivatives of the compounds of formula (I) such as the compounds quaternised by compounds R x -T wherein R x is C 1-6 alkyl, phenyl-C 1-6 alkyl or C 5 -7 cycloalkyl, and T is a radical corresponding to an anion of an acid.
  • R ⁇ include methyl, ethyl and n- and iso-propyl; and benzyl and phenethyl.
  • Suitable examples of T include halide such as chloride, bromide and iodide.
  • Examples of pharmaceutically acceptable salts also include internal salts such as N-oxides.
  • the compounds of the formula (I), their pharmaceutically acceptable salts, (including quaternary derivatives and N-oxides) may also form pharmaceutically acceptable
  • X-CO-Y- in compounds of formula (I) may adopt an ⁇ or ⁇ or configuration with respect to Z.
  • the compounds of formula (I) are prepared by linking
  • azabicyclic side chain intermediates may be prepared from the corresponding ketones of formula (II) and (III):
  • the ketones of the formula (II) may be prepared according to the method described by G. H. Dewar, R.T. Parfitt, L. Sheh; Eur. J. Med. Chem., 1985, 20 , 228, and the ketone of formula (III) may be prepared according to the method described in the Description 2 hereinafter.
  • the compounds of the present invention are 5-HT 3 receptor antagonists and it is thus believed may generally be used in the treatment or prophylaxis of pain, emesis, CNS disorders and gastrointestinal disorders. Pain includes migraine, cluster headache, trigeminal neuralgia and visceral pain; emesis, includes, in particular, that of preventing vomiting and nausea associated with cancer therapy, post-operative emesis, and nausea associated with migraine.
  • cancer therapy examples include that using cytotoxic agents, such as platinum complexes including cisplatin, and also doxorubicin and cyclophosphamide, particularly cisplatin; and also radiation treatment.
  • CNS disorders include anxiety, psychosis, cognitive disorders such as senile dementia and age associated memory impairment (AAMI), and drug dependence.
  • Gastrointestinal disorders include irritable bowel syndrome and diarrohea.
  • 5-HT 3 receptor antagonists may also be of potential use in the treatment of obesity, arrhythmia, and/or disorders associated with myocardial instability.
  • the invention also provides a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
  • compositions are prepared by admixture and are usually adapted for oral or parenteral administration, and as such may be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable and infusable solutions or suspensions or suppositories .
  • Orally administrable compositions are preferred, since they are more convenient for general use.
  • Tablets and capsules for oral administration are usually presented in a unit dose, and contain conventional
  • excipients such as binding agents, fillers, diluents, tabletting agents, lubricants, disintegrants, colourants, flavourings, and wetting agents.
  • the tablets may be coated according to well known methods in the art, for example with an enteric coating.
  • Suitable fillers for use include cellulose, mannitol, lactose and other similar agents.
  • Suitable disintegrants include starch, polyvinylpolypyrrolidone and starch
  • Suitable lubricants include, for example, magnesium stearate.
  • Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulphate.
  • Oral liquid preparations may be in the form of, for example, aqueous or oily suspensions, solutions, emulsions, syrups, or elixirs, or may be
  • Such liquid preparations may contain conventional additives such as suspending agents, for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminium stearate gel or hydrogenated edible fats,
  • suspending agents for example sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminium stearate gel or hydrogenated edible fats,
  • emulsifying agents for example lecithin, sorbitan
  • non-aqueous vehicles which may include edible oils, for example, almond oil, fractionated coconut oil, oily esters such as esters of glycerine, propylene glycol, or ethyl alcohol; preservatives, for example methyl or propyl p-hydroxybenzoate or sorbic acid, and if desired conventional flavouring or colouring agents.
  • Oral liquid preparations are usually in the form of aqueous or oily suspensions, solutions, emulsions, syrups, or elixirs or are presented as a dry product for reconstitution with water or other suitable vehicle before use.
  • Such liquid preparations may contain conventional additives such as suspending agents, emulsifying agents, non-aqueous vehicles (which may include edible oils), preservatives, and flavouring or colouring agents.
  • the oral compositions may be prepared by conventional methods of blending, filling or tabletting. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large
  • fluid unit dose forms are prepared containing a compound of the present invention and a sterile vehicle.
  • the compound depending on the vehicle and the concentration, can be either suspended or dissolved.
  • Parenteral solutions are normally prepared by dissolving the compound in a vehicle and filter sterilising before filling into a suitable vial or ampoule and sealing.
  • adjuvants such as a local anaesthetic, preservatives and buffering agents are also dissolved in the vehicle.
  • the composition can be frozen after filling into the vial and the water removed under vacuum.
  • Parenteral suspensions are prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilised by
  • a surfactant or wetting agent is included in the composition to facilitate uniform
  • the invention further provides a method of treatment or prophylaxis of pain, emesis, CNS disorders and/or
  • gastrointestinal disorders in mammals such as humans, which comprises the administration of an effective amount of a compound of the formula (I) or a pharmaceutically acceptable salt thereof.
  • a unit dose for a 70kg adult will normally contain 0.05 to 1000mg for example 0.5 to 500mg, of the compound of the invention.
  • Unit doses may be administered once or more than once a day, for example, 2, 3 or 4 times a day, more usually 1 to 3 times a day, that is in the range of approximately 0.0001 to 50mg/kg/day, more usually 0.0002 to 25 mg/kg/day.
  • the invention also provides a compound of formula (I) or a pharmaceutically acceptable salt thereof for use as an active therapeutic substance, in particular for use in the treatment of pain, emesis, CNS disorders and/or
  • the oxime (1.97g, 0.012mol) was dissolved in amyl alcohol (80ml) and heated to reflux under N 2 .
  • Sodium metal (6.5g, 0.28mol) was added portionwise over a 20 minute period and heating was continued for a further 1.5h.
  • the solution was allowed to cool slightly and water (20ml) was added
  • Compounds are given intravenously and the concentration required to reduce the 5-HT-evoked response to 50% of the control response (ED 50 ) is then determined.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Composés correspondant à la formule (I): X-A-Z, et leur sel acceptable pharmaceutiquement dans laquelle Z présente la structure (a) ou (b), dans laquelle X représente un groupe phényle ou un groupe hétéroaryle monocyclique à 5 ou 6 éléments, l'un ou l'autre de ces groupes étant éventuellement fusionné avec un noyau hétérocyclique ou carbocyclique saturé ou insaturé et comportant entre 5 et 7 éléments; A représente une fraction de liaison; et R représente hydrogène ou méthyle. Lesdits composés présentent une activité antagoniste au récepteur de 5-HT3.
PCT/GB1992/000050 1991-01-09 1992-01-09 Derives azabicydiques et azatricydiques, leurs procedes et intermediaires de preparation et compositions pharmaceutiques les contenant WO1992012149A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP4502573A JPH06506443A (ja) 1991-01-09 1992-01-09 アザ二環式およびアザ三環式誘導体、その製法および中間体ならびに該化合物含有の医薬組成物

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB919100370A GB9100370D0 (en) 1991-01-09 1991-01-09 Pharmaceuticals
GB9100370.7 1991-01-09
GB919100580A GB9100580D0 (en) 1991-01-10 1991-01-10 Pharmaceuticals
GB9100580.1 1991-01-10

Publications (1)

Publication Number Publication Date
WO1992012149A1 true WO1992012149A1 (fr) 1992-07-23

Family

ID=26298233

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1992/000050 WO1992012149A1 (fr) 1991-01-09 1992-01-09 Derives azabicydiques et azatricydiques, leurs procedes et intermediaires de preparation et compositions pharmaceutiques les contenant

Country Status (4)

Country Link
EP (1) EP0566609A1 (fr)
JP (1) JPH06506443A (fr)
AU (1) AU1161292A (fr)
WO (1) WO1992012149A1 (fr)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994001095A2 (fr) * 1992-07-03 1994-01-20 Smithkline Beecham Plc Medicaments pour le traitement de douleurs viscerales et de migraines
EP0645391A2 (fr) * 1993-07-30 1995-03-29 Eisai Co., Ltd. Dérivés d'acide aminobenzoique
WO1999017755A2 (fr) * 1997-10-07 1999-04-15 Glaxo Group Limited Medicaments
EP1018512A1 (fr) * 1998-10-13 2000-07-12 Rotta Research Laboratorium S.P.A. Nouveaux dérivés basiques des benz(e)isoindol-1-ones et pyrrolo(3,4-c)quinolin-1-ones ayant une activité antagoniste 5-HT3, leur préparation and leur utilisation thérapeutique
WO2003080046A1 (fr) * 2002-03-21 2003-10-02 Merz Pharma Gmbh & Co. Kgaa Derives azabicycliques, azatricycliques et azaspirocycliques d'aminocyclohexanes comme antagonistes des recepteurs de nmda, des recepteurs de 5ht3 et des recepteurs nicotiniques neuronaux
US6984652B2 (en) 2003-09-05 2006-01-10 Warner-Lambert Company Llc Gyrase inhibitors
US7396833B2 (en) 2003-12-22 2008-07-08 Memory Pharmaceuticals Corporation Indoles, 1H-indazoles, 1,2-benzisoxazoles, and 1,2-benzisothiazoles, and preparation and uses thereof
US7429664B2 (en) 2002-09-25 2008-09-30 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof
US7488737B2 (en) 2004-04-22 2009-02-10 Memory Pharmaceutical Corporation Indoles, 1H-indazoles, 1,2-benzisoxazoles, 1,2-benzoisothiazoles, and preparation and uses thereof
US7589109B2 (en) 2005-02-22 2009-09-15 Pfizer Inc Oxyindole derivatives
US7595329B2 (en) 2004-06-15 2009-09-29 Pfizer Inc Benzimidazolone carboxylic acid derivatives
US7625924B2 (en) 2004-12-22 2009-12-01 Memory Pharmaceuticals Corporation Nicotinic alpha-7 receptor ligands and preparation and uses thereof
US7632831B2 (en) 2004-05-07 2009-12-15 Memory Pharmaceuticals Corporation 1H-indazoles, benzothiazoles, 1,2-benzoisoxazoles, 1,2-benzoisothiazoles, and chromones and preparation and uses thereof
US7737163B2 (en) 2004-06-15 2010-06-15 Pfizer Inc. Benzimidazolone carboxylic acid derivatives
US8106066B2 (en) 2005-09-23 2012-01-31 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof
US8263619B2 (en) 2004-03-25 2012-09-11 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and uses thereof
WO2022175402A1 (fr) 2021-02-18 2022-08-25 Aprea Therapeutics Ab Dérivés de quinuclidine-3-one

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101106517B1 (ko) 2006-10-11 2012-01-20 닛뽕소다 가부시키가이샤 피페리딘-4-온 유도체의 제조 방법

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0013138A1 (fr) * 1978-12-30 1980-07-09 Beecham Group Plc Dérivés azabicycloalcoyle, procédé pour leur préparation et compositions pharmaceutiques les contenant

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0013138A1 (fr) * 1978-12-30 1980-07-09 Beecham Group Plc Dérivés azabicycloalcoyle, procédé pour leur préparation et compositions pharmaceutiques les contenant

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Chemical Abstracts, vol. 114, 1991, (Columbus, Ohio, US), see Abstract and Chemical Substance Index, page 700, column 1, lines 62,77-79, J. FENG et al.: "A screening test for Boajiasu derivatives", see page 22, abstract no. 220761m, & SHANGHAI DIER YIKE DAXUE XUEBAO 1990, 10(4), 324-6 *

Cited By (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994001095A2 (fr) * 1992-07-03 1994-01-20 Smithkline Beecham Plc Medicaments pour le traitement de douleurs viscerales et de migraines
WO1994001095A3 (fr) * 1992-07-03 1994-04-14 Smithkline Beecham Plc Medicaments pour le traitement de douleurs viscerales et de migraines
EP0645391A2 (fr) * 1993-07-30 1995-03-29 Eisai Co., Ltd. Dérivés d'acide aminobenzoique
EP0645391A3 (fr) * 1993-07-30 1995-05-24 Eisai Co Ltd Dérivés d'acide aminobenzoique.
US5512579A (en) * 1993-07-30 1996-04-30 Eisai Co., Ltd. Aminobenzoic acid derivatives
US5658925A (en) * 1993-07-30 1997-08-19 Eisai Co., Ltd. Aminobenzoic acid derivatives
US5677311A (en) * 1993-07-30 1997-10-14 Eisai Co., Ltd. Aminobenzoic acid derivatives
US5723472A (en) * 1993-07-30 1998-03-03 Eisai Co., Ltd. Aminobenzoic acid derivatives
US5861418A (en) * 1993-07-30 1999-01-19 Eisai Co., Ltd. Aminobenzoic acid derivatives
WO1999017755A3 (fr) * 1997-10-07 1999-09-23 Glaxo Group Ltd Medicaments
US6284770B1 (en) 1997-10-07 2001-09-04 Glaxo Wellcome Inc. Medicaments for the treatment of non-constipated female irritable bowel syndrome
AU750818B2 (en) * 1997-10-07 2002-07-25 Glaxo Group Limited Medicaments
US6429209B2 (en) 1997-10-07 2002-08-06 Smithkline Beecham Corporation Methods for treating irritable bowel syndrome
US6593336B2 (en) 1997-10-07 2003-07-15 Smithkline Beecham Corporation Methods for treating irritable bowel syndrome
WO1999017755A2 (fr) * 1997-10-07 1999-04-15 Glaxo Group Limited Medicaments
EP1018512A1 (fr) * 1998-10-13 2000-07-12 Rotta Research Laboratorium S.P.A. Nouveaux dérivés basiques des benz(e)isoindol-1-ones et pyrrolo(3,4-c)quinolin-1-ones ayant une activité antagoniste 5-HT3, leur préparation and leur utilisation thérapeutique
US6323216B1 (en) 1998-10-13 2001-11-27 Rotta Research Laboratorium S.P.A Basic derivatives of benz[E]isoindol-1-ones and pyrrolo[3,4-c]quinolin-1-ones with 5-HT3-antagonistic activity, their preparation and their therapeutic use
US6413978B1 (en) 1998-10-13 2002-07-02 Rotta Research Laboratorium S.P.A. Basic derivatives of benz[e] isoindol-1-ones and pyrrolo[3,4-c] quinolin-1-ones with 5-HT3-antagonistic activity, their preparation and their therapeutic use
US7238703B2 (en) 2002-03-21 2007-07-03 Merz Pharma Gmbh & Co. Kgaa Azabicyclic, azatricyclic and azaspirocyclic derivatives of aminocyclohexane NMDA, 5HT3, and neuronal nicotinic receptor antagonists
WO2003080046A1 (fr) * 2002-03-21 2003-10-02 Merz Pharma Gmbh & Co. Kgaa Derives azabicycliques, azatricycliques et azaspirocycliques d'aminocyclohexanes comme antagonistes des recepteurs de nmda, des recepteurs de 5ht3 et des recepteurs nicotiniques neuronaux
US7022729B2 (en) 2002-03-21 2006-04-04 Merz Pharma Gmbh & Co. Kgaa Azabicyclic, azatricyclic and azaspirocyclic derivatives of aminocyclohexane NMDA, 5HT3, and neuronal nicotinic receptor antagonists
US7943773B2 (en) 2002-09-25 2011-05-17 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof
US7429664B2 (en) 2002-09-25 2008-09-30 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof
US8252811B2 (en) 2002-09-25 2012-08-28 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof
US8134003B2 (en) 2002-09-25 2012-03-13 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof
US6984652B2 (en) 2003-09-05 2006-01-10 Warner-Lambert Company Llc Gyrase inhibitors
US8158629B2 (en) 2003-12-22 2012-04-17 Memory Pharmaceuticals Corporation Indoles, 1H-indazoles, 1,2-benzisoxazoles, and 1,2-benzisothiazoles, and preparation and uses thereof
US7964600B2 (en) 2003-12-22 2011-06-21 Memory Pharmaceuticals Corporation Indoles, 1H-indazoles, 1,2-benzisoxazoles, and 1,2-benzisothiazoles, and preparation and uses thereof
US7790722B2 (en) 2003-12-22 2010-09-07 Memory Pharmaceuticals Corporation Indoles, 1H-indazoles, 1,2-benzisoxazoles, and 1,2-benzisothiazoles, and preparation and uses thereof
US7396833B2 (en) 2003-12-22 2008-07-08 Memory Pharmaceuticals Corporation Indoles, 1H-indazoles, 1,2-benzisoxazoles, and 1,2-benzisothiazoles, and preparation and uses thereof
US8691841B2 (en) 2004-03-25 2014-04-08 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and use thereof
US8486937B2 (en) 2004-03-25 2013-07-16 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and use thereof
US8263619B2 (en) 2004-03-25 2012-09-11 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and uses thereof
US7902217B2 (en) 2004-04-22 2011-03-08 Memory Pharmaceuticals Corporation Indoles, 1H-indazoles, 1,2-benzisoxazoles, 1,2-benzoisothiazoles, and preparation and uses thereof
US7488737B2 (en) 2004-04-22 2009-02-10 Memory Pharmaceutical Corporation Indoles, 1H-indazoles, 1,2-benzisoxazoles, 1,2-benzoisothiazoles, and preparation and uses thereof
US7632831B2 (en) 2004-05-07 2009-12-15 Memory Pharmaceuticals Corporation 1H-indazoles, benzothiazoles, 1,2-benzoisoxazoles, 1,2-benzoisothiazoles, and chromones and preparation and uses thereof
US7737163B2 (en) 2004-06-15 2010-06-15 Pfizer Inc. Benzimidazolone carboxylic acid derivatives
US7705020B2 (en) 2004-06-15 2010-04-27 Pfizer Inc. Benzimidazolone carboxylic acid derivatives
US7595329B2 (en) 2004-06-15 2009-09-29 Pfizer Inc Benzimidazolone carboxylic acid derivatives
US7625924B2 (en) 2004-12-22 2009-12-01 Memory Pharmaceuticals Corporation Nicotinic alpha-7 receptor ligands and preparation and uses thereof
US7589109B2 (en) 2005-02-22 2009-09-15 Pfizer Inc Oxyindole derivatives
US8106066B2 (en) 2005-09-23 2012-01-31 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof
US8273891B2 (en) 2006-09-22 2012-09-25 Memory Pharmaceuticals Corporation Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof
WO2022175402A1 (fr) 2021-02-18 2022-08-25 Aprea Therapeutics Ab Dérivés de quinuclidine-3-one

Also Published As

Publication number Publication date
EP0566609A1 (fr) 1993-10-27
JPH06506443A (ja) 1994-07-21
AU1161292A (en) 1992-08-17

Similar Documents

Publication Publication Date Title
WO1992012149A1 (fr) Derives azabicydiques et azatricydiques, leurs procedes et intermediaires de preparation et compositions pharmaceutiques les contenant
AU626614B2 (en) 9-aza-3(oxa or thio)bicyclo(3.3.1)nonane derivatives
US4789673A (en) Heterocyclic carboxylic acid amides and esters
EP0315390B1 (fr) Composés nouveaux de 4-oxobenzotriazine et 4-oxoquinazoline
WO1992014733A1 (fr) Produits pharmaceutiques
EP0254584B1 (fr) Composés azabicycliques, procédé pour leur préparation et leur utilisation pharmaceutique
AU7753991A (en) Isoquinoline amides and esters as 5 ht3 receptor antagonists
US4882327A (en) Certain heterocyclic N-substituted carboxamides
IE58313B1 (en) Azabicyclononyl-indazole-carboxamide having 5-ht antagonist activity
GB2166726A (en) Substituted benzoic acid alkylene bridged piperidyl amides
KR20030009376A (ko) 3-(디아릴메틸렌)-8-아자비사이클로[3.2.1]옥탄 유도체
JP2643274B2 (ja) イミダゾ〔１，２−ａ〕ピリジン誘導体
AU652187B2 (en) 3,9-diazabicyclo (3.3.1) nonan-7-YL derivatives, process and intermediates for their preparation and pharmaceutical compositions containing them
EP0459568A2 (fr) Oxadiazoles et thiadiazoles substitués comme médicaments dans le traitement du glaucome et nouveaux composés à cet usage
EP0560604B1 (fr) Dérivés d&#39;acide cinnoline-3-carboxyliques comme 5-HT3 antagonistes
WO1993008185A1 (fr) N-aryle-n1-azabicyclo-urees utilisees comme antagonistes de 5-ht3
WO1993007147A1 (fr) Derives de 3,9-diazobicyclo(3.3.1)nonane presentant une activite antagoniste du recepteur 5-ht¿3?
US6727249B2 (en) Azabicyclic ether derivatives and their use as therapeutic agents
EP0611370A1 (fr) Amides ou esters d&#39;acide pyridine-3-carboxylique utilises comme antagonistes de 5-ht 3?

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU CA JP KR US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IT LU MC NL SE

WWE Wipo information: entry into national phase

Ref document number: 1992902098

Country of ref document: EP

ENP Entry into the national phase

Ref country code: US

Ref document number: 1993 87702

Date of ref document: 19930709

Kind code of ref document: A

Format of ref document f/p: F

WWP Wipo information: published in national office

Ref document number: 1992902098

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: CA

WWW Wipo information: withdrawn in national office

Ref document number: 1992902098

Country of ref document: EP