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WO1992010494A1 - Composes pharmaceutiques - Google Patents

Composes pharmaceutiques Download PDF

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Publication number
WO1992010494A1
WO1992010494A1 PCT/GB1991/002173 GB9102173W WO9210494A1 WO 1992010494 A1 WO1992010494 A1 WO 1992010494A1 GB 9102173 W GB9102173 W GB 9102173W WO 9210494 A1 WO9210494 A1 WO 9210494A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound according
compound
formula
pharmaceutically acceptable
acceptable salt
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.)
Ceased
Application number
PCT/GB1991/002173
Other languages
English (en)
Inventor
Francis David King
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Beecham Group PLC
Original Assignee
Beecham Group 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
Application filed by Beecham Group PLC filed Critical Beecham Group PLC
Priority to JP4501711A priority Critical patent/JPH06503331A/ja
Priority to AU90783/91A priority patent/AU651645B2/en
Publication of WO1992010494A1 publication Critical patent/WO1992010494A1/fr
Priority to KR1019930701776A priority patent/KR930703307A/ko
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • 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
    • C07D451/04—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 with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • 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
    • C07D451/14—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 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/06—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing isoquinuclidine ring systems

Definitions

  • This invention relates to novel compounds having
  • the present invention provides a compound of formula (I), or a pharmaceutically acceptable salt thereof:
  • R 1 is hydrogen, halo, nitro, amino, C 1-6 alkyl or C 1-6
  • R 2 is halo, C 1-6 alkyl or C 1-6 alkoxy
  • A is (poly)methylene of 1-3 carbon atoms, optionally
  • L is O or NH
  • Z is a di-azacyclic or azabicyclic side chain
  • alkyl moieties in R 1 and R 2 and A include methyl, ethyl, n- and iso-propyl, n-, iso-, sec- an tert-butyl.
  • Suitable examples of halo moieties include fluoro, chloro and bromo, preferably chloro or bromo.
  • R 1 is hydrogen and R 2 is chloro or bromo.
  • A is preferably unsubstituted polymethylene of 1 or 2 carbo atoms (i.e. O-A-O is methylenedioxy or ethylenedioxy).
  • Suitable examples of Z are described in the art relating to 5-HT 3 receptor antagonists, ie. as follows: i) GB 2125398A (Sandoz Limited)
  • EP-A-215545 (Beecham Group p.l.c.)
  • EP-A-214772 (Beecham Group p.I.c.)
  • R is hydrogen or methyl; and X is oxygen, sulphur or
  • cycloalkyl C 3-8 cycloalkyl C 1-4 alkyl, phenyl, naphthyl, phenyl C 1-4 alkyl or naphthyl C 1-4 alkyl wherein a phenyl or naphthyl moiety is optionally substituted by one or more of halo, C 1-6 alkoxy or C 1-6 alkyl.
  • Side chains Z of particular interest include tropane, oxagranatane and azagranatane, where R is methyl.
  • Suitable values for N-substituents when X is N are as described in PCT/GB91/01629, for example, iso-propyl or ethyl.
  • L is preferably NH.
  • COL in formula (I) may be replaced by a bioisostere therefor, for example, 1,2,4-oxadiazole and the other groups of structure h) described in EP-A-377967
  • the pharmaceutically acceptable salts of the compounds of the formula (I) include acid addition salts with
  • the pharmaceutically acceptable salts of the compounds of the formula (I) are usually acid addition salts with acids such as hydrochloric, hydrobromic, phosphoric, sulphuric, citric, tartaric, lactic and acetic acid.
  • the acid addition salt is the hydrochloride salt.
  • 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 x 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
  • the invention also provides a process for the preparation of a compound of formula (I), or a pharmaceutically acceptable salt thereof, which process comprises reacting a compound of formula (II):
  • nucleophile include halogen such as chloro and bromo, C 1-4 alkoxy, such as CH 3 O and C 2 H 5 O-, PhO-, activated
  • hydrocarbyloxy such as Cl 5 C 6 O- or Cl 3 CO-
  • a nitrogen- linked heterocycle such as imidazole.
  • reaction is preferably carried out at non-extreme temperatures in an inert
  • non-hydroxylic solvent such as benzene, dichloromethane, toluene, diethyl ether, tetrahydrofuran (THF) or dimethylformamide (DMF). It is also preferably carried out in the presence of an acid acceptor, such as an organic base, in particular a tertiary amine, such as triethylamine, trimethylamine, pyridine or picoline, some of which can also function as the solvent.
  • the acid acceptor can be inorganic, such as calcium carbonate, sodium
  • reaction is preferably carried out in an inert polar solvent, such as toluene
  • the compound of formula (III) may be in the form of a reactive derivative thereof, which is often a salt, such as the lithium, sodium or potassium salt.
  • Z' when other than Z may be wherein R is replaced by R' which is a hydrogenolysable protecting group which is benzyl optionally substituted by one or two groups selected from halo, C 1-4 alkoxy and C 1-4 alkyl.
  • R' which is a hydrogenolysable protecting group which is benzyl optionally substituted by one or two groups selected from halo, C 1-4 alkoxy and C 1-4 alkyl.
  • Such benzyl groups may, for example, be removed, when R 1 /R 2 is not halogen, by conventional transition metal catalysed hydrogenolysis to give compounds of the formula (I) wherein R is hydrogen.
  • This invention also provides a further process for the preparation of a compound of the formula (I) wherein R is methyl or a pharmaceutically acceptable salt thereof, which comprises N-methylating a compound of formula (I) wherein R is hydrogen, and optionally forming a pharmaceutically acceptable salt of the resulting compound of the formula (I).
  • a further process for the preparation of a compound of the formula (I) wherein R is methyl or a pharmaceutically acceptable salt thereof which comprises N-methylating a compound of formula (I) wherein R is hydrogen, and optionally forming a pharmaceutically acceptable salt of the resulting compound of the formula (I).
  • 'N-methylation' may be achieved by reaction with a compound CH 3 Q 3 wherein Q 3 is a leaving group.
  • Suitable values for Q 3 include groups displaced by
  • nucleophiles such as Cl, Br, I, OSO 2 CH 3 or OSO 2 C 6 H 4 pCH 3 , preferably Cl, Br or I.
  • the reaction may be carried out under conventional
  • alkylation conditions for example in an inert solvent such as dimethylformamide in the presence of an acid acceptor such as potassium carbonate.
  • an acid acceptor such as potassium carbonate.
  • the reaction is carried out at non-extreme temperature such as at ambient slightly above.
  • 'N-methylation' may be effected under
  • Interconverting R in the compound of the formula (III) before coupling with the compound of the formula (II) is also possible. Such interconversions are effected
  • Such compounds may then be reduced using a strong reductant such as lithium aluminium hydride to the corresponding compound of formula (II).
  • the compounds of formula (II) are known or are preparable analogously to, or routinely from, known compounds, such as described in UK 1571278.
  • azabicyclic side chain prepared by condensation methods, often using a substituted piperidine.
  • the -COL- linkage has an endo orientation with respect to the ring of the bicyclic moiety to which it is attached.
  • a mixture of endo and exo isomers of the compound of the formula (I) may be synthesised non-stereospecifically and the desired isomer separated conventionally therefrom e.g. by chromatography; or alternatively the endo isomer may if desired by synthesised from the corresponding endo form of the compound of the formula (II).
  • the salts may be formed for example by reaction of the base compound of formula (I) with a pharmaceutically acceptable organic or inorganic acid.
  • the compounds of the present invention are 5-HT3 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. Examples of such cancer therapy 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
  • Gastrointestinal disorders include depression, anxiety, psychosis, cognitive disorders such as senile dementia and age associated memory impairment (AAMI), and drug dependence. Gastrointestinal disorders include
  • 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
  • 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.
  • 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, a 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 quantities of fillers. Such operations are, of course, conventional in the art.
  • fluid unit dose forms are prepared containing a compound of the present invention an a sterile vehicle.
  • the compound depending on the vehicle and the concentration, can be either suspended or dissolve
  • Parenteral solutions are normally prepared by dissolving th 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 th 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 exposure of ethylene oxide before suspending in the sterile vehicle.
  • 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 acceptabl 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
  • 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 compounds of the Examples are both active at a dose of 10 ⁇ g/kg i.v.

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

Composés de la formule (I) et sels pharmaceutiquement acceptables de ces composés où les groupes variables sont tels qu'ils sont définis dans le descriptif.
PCT/GB1991/002173 1990-12-13 1991-12-06 Composes pharmaceutiques Ceased WO1992010494A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
JP4501711A JPH06503331A (ja) 1990-12-13 1991-12-06 医薬品
AU90783/91A AU651645B2 (en) 1990-12-13 1991-12-06 Pharmaceuticals
KR1019930701776A KR930703307A (ko) 1990-12-13 1993-06-12 제약품

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB909027098A GB9027098D0 (en) 1990-12-13 1990-12-13 Pharmaceuticals
GB9027098.4 1990-12-13

Publications (1)

Publication Number Publication Date
WO1992010494A1 true WO1992010494A1 (fr) 1992-06-25

Family

ID=10686972

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1991/002173 Ceased WO1992010494A1 (fr) 1990-12-13 1991-12-06 Composes pharmaceutiques

Country Status (12)

Country Link
EP (1) EP0561910A1 (fr)
JP (1) JPH06503331A (fr)
KR (1) KR930703307A (fr)
AU (1) AU651645B2 (fr)
CA (1) CA2098309A1 (fr)
GB (1) GB9027098D0 (fr)
IE (1) IE914315A1 (fr)
MX (1) MX9102499A (fr)
NZ (1) NZ240938A (fr)
PT (1) PT99771A (fr)
WO (1) WO1992010494A1 (fr)
ZA (1) ZA919756B (fr)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5620992A (en) * 1992-09-10 1997-04-15 Smithkline Beecham Plc Heteroaryl compounds used as pharmaceuticals
WO1999017755A3 (fr) * 1997-10-07 1999-09-23 Glaxo Group Ltd Medicaments
US6376535B2 (en) 1998-09-03 2002-04-23 Kyowa Hakko Kogyo Co., Ltd. Oxygen-containing heterocyclic compounds
US6828330B2 (en) 2001-06-12 2004-12-07 Pharmacia & Upjohn Company Quinuclidine-substituted hetero-bicyclic aromatic compounds for the treatment of disease
US6849620B2 (en) 2001-10-26 2005-02-01 Pfizer Inc N-(azabicyclo moieties)-substituted hetero-bicyclic aromatic compounds for the treatment of disease
US6858613B2 (en) 2002-02-19 2005-02-22 Pfizer Inc. Fused bicyclic-N-bridged-heteroaromatic carboxamides for the treatment of disease
US6894042B2 (en) 2002-02-19 2005-05-17 Pharmacia & Upjohn Company Azabicyclic compounds for the treatment of disease
US6911543B2 (en) 2001-10-02 2005-06-28 Pfizer Inc. Azabicyclic-substituted fused-heteroaryl compounds for the treatment of disease
US6951868B2 (en) 2001-11-09 2005-10-04 Pfizer Inc. Azabicyclic-phenyl-fused-heterocyclic compounds for treatment of disease
US7067515B2 (en) 2001-06-12 2006-06-27 Pfizer Inc. Quinuclidines-substituted-multi-cyclic-heteroaryls for the treatment of disease

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1571447A (en) * 1976-08-04 1980-07-16 Ile De France Substituted 2,3-alkyleneduoxybenzamides
EP0041817A1 (fr) * 1980-06-10 1981-12-16 Beecham Group Plc Dérivés de la benzamide, procédé pour leur préparation et compositions pharmaceutiques les contenant
EP0083737A1 (fr) * 1981-12-15 1983-07-20 Beecham Group Plc N-azabicycloalcan benzamides, procédé de préparation et les compositions pharmaceutiques les contenant
CH651561A5 (fr) * 1980-11-07 1985-09-30 Delalande Sa Derives des nor-tropane et granatane et leur procede de preparation.
EP0226267A1 (fr) * 1985-07-19 1987-06-24 Beecham Group Plc Dérivés d'oxa-, thia- et diazabicycloalcane, leur procédé de préparation et leur utilisation comme médicaments
EP0377967A2 (fr) * 1988-12-13 1990-07-18 Beecham Group Plc Dérivés du 9-aza-3-(oxa/thia)-bicyclo[3,2,1]nonane, procédé et intermédiaires pour leur préparation et compositions pharmaceutiques les contenant

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MC1154A1 (fr) * 1976-08-04 1978-04-17 Ile De France Nouveaux 2,3-alkylene bis(oxy)benzamides substitues,leurs derives et leurs procedes de preparation

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1571447A (en) * 1976-08-04 1980-07-16 Ile De France Substituted 2,3-alkyleneduoxybenzamides
EP0041817A1 (fr) * 1980-06-10 1981-12-16 Beecham Group Plc Dérivés de la benzamide, procédé pour leur préparation et compositions pharmaceutiques les contenant
CH651561A5 (fr) * 1980-11-07 1985-09-30 Delalande Sa Derives des nor-tropane et granatane et leur procede de preparation.
EP0083737A1 (fr) * 1981-12-15 1983-07-20 Beecham Group Plc N-azabicycloalcan benzamides, procédé de préparation et les compositions pharmaceutiques les contenant
EP0226267A1 (fr) * 1985-07-19 1987-06-24 Beecham Group Plc Dérivés d'oxa-, thia- et diazabicycloalcane, leur procédé de préparation et leur utilisation comme médicaments
EP0377967A2 (fr) * 1988-12-13 1990-07-18 Beecham Group Plc Dérivés du 9-aza-3-(oxa/thia)-bicyclo[3,2,1]nonane, procédé et intermédiaires pour leur préparation et compositions pharmaceutiques les contenant

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5620992A (en) * 1992-09-10 1997-04-15 Smithkline Beecham Plc Heteroaryl compounds used as pharmaceuticals
US5786372A (en) * 1992-09-10 1998-07-28 Smithkline Beecham P.L.C. Heteroaryl compounds used as pharmaceuticals
US6593336B2 (en) 1997-10-07 2003-07-15 Smithkline Beecham Corporation Methods for treating irritable bowel syndrome
US6284770B1 (en) 1997-10-07 2001-09-04 Glaxo Wellcome Inc. Medicaments for the treatment of non-constipated female irritable bowel syndrome
US6429209B2 (en) 1997-10-07 2002-08-06 Smithkline Beecham Corporation Methods for treating irritable bowel syndrome
WO1999017755A3 (fr) * 1997-10-07 1999-09-23 Glaxo Group Ltd Medicaments
US6376535B2 (en) 1998-09-03 2002-04-23 Kyowa Hakko Kogyo Co., Ltd. Oxygen-containing heterocyclic compounds
US6828330B2 (en) 2001-06-12 2004-12-07 Pharmacia & Upjohn Company Quinuclidine-substituted hetero-bicyclic aromatic compounds for the treatment of disease
US7067515B2 (en) 2001-06-12 2006-06-27 Pfizer Inc. Quinuclidines-substituted-multi-cyclic-heteroaryls for the treatment of disease
US6911543B2 (en) 2001-10-02 2005-06-28 Pfizer Inc. Azabicyclic-substituted fused-heteroaryl compounds for the treatment of disease
US6849620B2 (en) 2001-10-26 2005-02-01 Pfizer Inc N-(azabicyclo moieties)-substituted hetero-bicyclic aromatic compounds for the treatment of disease
US6951868B2 (en) 2001-11-09 2005-10-04 Pfizer Inc. Azabicyclic-phenyl-fused-heterocyclic compounds for treatment of disease
US6858613B2 (en) 2002-02-19 2005-02-22 Pfizer Inc. Fused bicyclic-N-bridged-heteroaromatic carboxamides for the treatment of disease
US6894042B2 (en) 2002-02-19 2005-05-17 Pharmacia & Upjohn Company Azabicyclic compounds for the treatment of disease

Also Published As

Publication number Publication date
EP0561910A1 (fr) 1993-09-29
NZ240938A (en) 1994-08-26
KR930703307A (ko) 1993-11-29
CA2098309A1 (fr) 1992-06-14
AU9078391A (en) 1992-07-08
GB9027098D0 (en) 1991-02-06
PT99771A (pt) 1992-11-30
AU651645B2 (en) 1994-07-28
ZA919756B (en) 1992-10-28
MX9102499A (es) 1992-06-01
JPH06503331A (ja) 1994-04-14
IE914315A1 (en) 1992-06-17

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