EP0724580A1 - Derives de benzanilide en tant qu'antagonistes du recepteur de 5ht-1d - Google Patents

Derives de benzanilide en tant qu'antagonistes du recepteur de 5ht-1d

Info

Publication number
EP0724580A1
EP0724580A1 EP94930171A EP94930171A EP0724580A1 EP 0724580 A1 EP0724580 A1 EP 0724580A1 EP 94930171 A EP94930171 A EP 94930171A EP 94930171 A EP94930171 A EP 94930171A EP 0724580 A1 EP0724580 A1 EP 0724580A1
Authority
EP
European Patent Office
Prior art keywords
formula
methyl
compound
dihydro
methylpiperazin
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP94930171A
Other languages
German (de)
English (en)
Inventor
Graham Francis Joiner
Laramie Mary Gaster
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.)
SmithKline Beecham Ltd
Original Assignee
SmithKline Beecham Ltd
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 GB939321490A external-priority patent/GB9321490D0/en
Priority claimed from GB939325866A external-priority patent/GB9325866D0/en
Application filed by SmithKline Beecham Ltd filed Critical SmithKline Beecham Ltd
Publication of EP0724580A1 publication Critical patent/EP0724580A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
    • C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • 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
    • A61P25/24—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
    • A61P25/26—Psychostimulants, e.g. nicotine, cocaine
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
    • C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
    • C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D319/18—Ethylenedioxybenzenes, not substituted on the hetero ring
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

  • the present invention relates to novel amide derivatives, processes for their preparation, and pharmaceutical compositions containing them.
  • EPA 0533 266/7/8 disclose a series of benzanilide derivatives which are said to possess 5HTID receptor antagonist activity. These compounds are said to be of use in the treatment of various CNS disorders.
  • the present invention therefore provides a compound of formula (I) or a salt thereof:
  • R.1 is halogen, C3_6cycloalkyl, optionally substituted phenyl or an optionally substituted 5-7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur;
  • R2 is hydrogen, halogen, C ⁇ galkyl, C ⁇ .g-alkoxy, acyl, nitro, trifluoromethyl or cyano;
  • R3 is hydrogen or Ci.galkyl;
  • A is -(CR 4 R 5 ) m - or -O(CR 4 R 5 ) n - where R 4 and R 5 are independently hydrogen or Ci.galkyl, m is 2, or 3; n is 1, 2 or 3 and B is CONH or NHCO.
  • the group R can be an aromatic or saturated heterocyclic ring. When R is an aromatic heterocyclic ring, examples of such rings include thienyl, furyl, pyrrolyl, triazolyl, diazolyl, imidazolyl, oxadiazolyl, isothiazolyl, isoxazolyl, thiadiazolyl, pyrimidyl and pyrazinyl.
  • R* is a saturated ring examples include piperidine, morpholine and piperazine rings.
  • the group R ⁇ can be linked to the remainder of the molecule via a carbon atom or, when present, a nitrogen atom.
  • R C3_6cycloalkyl groups include cyclohexyl.
  • the group R is attached to the 4-position of the phenyl ring, that is to say, para to the amide group.
  • Optional substituents for R include halogen, Ci.galkyl, C ⁇ _6alkoxy, hydroxy, cyano, nitro, amino, CO2R"
  • the group R can also be an optionally substituted phenyl group, in particular a phenyl group disubstituted by Ci.galkyl and an optionally substituted 5 to 7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur.
  • Preferred 5 to 7-membered heterocyclic rings include those listed above.
  • Preferred substituents for such rings include Ci.galkyl, in particular methyl.
  • R is halogen, pyridyl or a phenyl group disubstituted by a C .galkyl group and an optionally substituted 5-7 membered heterocyclic ring containing 1 to 3 heteroatoms selected from oxygen, nitrogen or sulphur. More preferably R* is a phenyl group disubstituted by methyl and an optionally substituted oxadiazolyl group, in particular an oxadiazolyl group substituted by Ci.galkyl. Most preferably R* is a group of formula:
  • R ⁇ is hydrogen, halogen, Ci.galkyl, Ci.galkoxy or nitro.
  • R ⁇ is hydrogen, methyl or nitro, most preferably hydrogen.
  • R ⁇ is hydrogen or Ci.galkyl.
  • R ⁇ is hydrogen or methyl.
  • A is CH2CH2 or OCH2CH2.
  • B is CONH.
  • Particularly preferred compounds include:
  • Ci.galkyl groups may be straight chain or branched.
  • Preferred salts of the compounds of formula (I) are pharmaceutically acceptable salts. These include acid addition salts such as hydrochlorides, hydrobromides, phosphates, acetates, fumarates, maleates, tartrates, citrates, oxalates, methanesulphonates and p-toluenesulphonates.
  • acid addition salts such as hydrochlorides, hydrobromides, phosphates, acetates, fumarates, maleates, tartrates, citrates, oxalates, methanesulphonates and p-toluenesulphonates.
  • Certain compounds of formula (I) are capable of existing in stereoisomeric forms. It will be understood that the invention encompasses all geometric and optical isomers of the compounds of formula (I) and the mixtures thereof including racemates. Tautomeric forms of compounds of formula (I) and mixtures thereof also form an aspect of the invention.
  • the present invention provides a process for the preparation of a compound of formula (I) which comprises.
  • R 1 , R 2 , R 3 and A are as defined in formula (I) and R 9 and R 10 contain the appropriate functional group(s) necessary to form the B moiety;
  • R 3 is as defined in formula (I) and Hal is halogen, or
  • R 2 , R 3 , A and B are as defined in formula (I) and Y is halogen or a group -OSO2CF3 with a compound of formula (VIII):
  • R 9 or R 1 ⁇ i an activated carboxylic acid derivative, such as an acyl halide or acid anhydride, and the other is an amine group.
  • Activated compounds of formulae (II) or (El) can also be prepared by reaction of the corresponding carboxylic acid with a coupling reagent such as carbonyldiimidazole, dicyclohexylcarbodiimide or diphenylphosphorylazole.
  • R 9 or RlO is a group COL where L is halo, particularly chloro.
  • a compound of formulae (II) and (HI) are typically reacted together in an inert organic solvent such as DMF, THF or dichloromethane at ambient or elevated temperature in the presence of a base such as triethylamine, pyridine or aqueous sodium hydroxide.
  • Compounds of formulae (II) and (III) can be prepared from the corresponding carboxylic acids using standard procedures.
  • acid chlorides can be prepared by reaction with phosphorous pentachloride, oxalyl chloride or thionyl chloride.
  • Acid anhydrides can be prepared by reaction with a suitable acid anhydride, for example trifluoroacetic anhydride.
  • Reaction of a compound of formula (IV) with a nucleophile R ⁇ is preferably carried out in a suitable solvent such as dimethylformamide in the presence of a strong base such as sodium hydride.
  • a strong base such as sodium hydride.
  • the leaving group X is halo, in particular fluoro.
  • the group R 2 is an electron withdrawing group, for example nitro, COCH3 or cyano, in the ortho or para-positions relative to the group X.
  • Reaction of a compound of formula (V) with a compound of formula (VI) is suitably carried out in an alcohol or nitrile solvent with an optional base or, alternatively, in a non-polar solvent such as chlorobenzene in the absence of base.
  • reaction of compounds of formula (VII) and (VIII) and reaction of compounds of formulae (IX) and (X) can be carried out in the presence of a transition metal catalyst such as Pd(PPh3)4 in a solvent such as an ether in the presence of a base such as an alkali metal carbonate or bicarbonate, for example sodium carbonate or bicarbonate, at ambient or elevated temperature.
  • a transition metal catalyst such as Pd(PPh3)4
  • a solvent such as an ether
  • a base such as an alkali metal carbonate or bicarbonate, for example sodium carbonate or bicarbonate
  • (X) are commercially available or can be prepared using standard procedures. For example certain compounds can be prepared using similar procedures to those outlined in EPA 533266/7/8.
  • Carboxylic acid groups can be protected as esters.
  • Aldehyde or ketone groups can be protected as acetals, ketals, thioacetals or thioketals. Deprotection is achieved using standard conditions.
  • 5HTID Antagonists, and in particular the compounds of the present invention are expected to be of use in the treatment of CNS disorders such as mood disorders, including depression, seasonal effective disorder and dysthymia; anxiety disorders, including generalised anxiety, panic disorder, agoraphobia, social phobia, obsessive compulsive disorder and post-traumatic stress disorder; memory disorders, including dementia, amnestic disorders and age-associated memory impairment; and disorders of eating behaviours, including anorexia nervosa and bulimia nervosa.
  • Other CNS disorders include Parkinson's disease, dementia in Parkinson's disease, neuroleptic-induced Parkinsonism and tardive dyskinesias, as well as other psychiatric disorders.
  • 5HTID Antagonists may also be of use in the treatment of endocrine disorders such as hyperprolactinaemia, in the treatment of vasospasm (particularly in the cerebral vasculature) and hypertension, as well as disorders in the gastrointestinal tract where changes in motility and secretion are involved. They may also be of use in the treatment of sexual dysfunction.
  • the present invention provides a compound of general formula (I) or a physiologically acceptable salt or solvate thereof for use in therapy.
  • the present invention also provides a compound of general formula (I) or a physiologically acceptable salt or solvate thereof for use in the treatment of the aforementioned disorders.
  • the invention provides the use of a compound of general formula (I) or a pharmaceutically acceptable salt or solvate thereof for the manufacture of a medicament for the treatment of the aforementioned disorders.
  • the invention provides a method of treating the aforementioned disorders which comprises administering an effective amount to a patient in need of such treatment of a compound of general formula (I) or a pharmaceutically acceptable salt or solvate thereof.
  • the invention provides a compound of general formula (I) or a physiologically acceptable salt or solvate thereof for use in the treatment or prophylaxis of depression.
  • the compounds according to the invention may advantageously be used in conjunction with one or more other therapeutic agents, for instance, different antidepressant agents.
  • the present invention also provides a pharmaceutical composition, which comprises a compound of formula (I) or a pharmaceutically acceptable salt thereof, and a
  • SUBS ⁇ TUTE SHEET (RULE 26) pharmaceutically acceptable carrier.
  • a pharmaceutical composition of the invention which may be prepared by admixture, suitably at ambient temperature and atmospheric pressure, is usually adapted for oral, parenteral or rectal administration and, as such, may be in the form of tablets, capsules, oral liquid preparations, powders, granules, lozenges, reconstitutable powders, injectable or infusible solutions or suspensions or suppositories. Orally administrable compositions are generally preferred.
  • Tablets and capsules for oral administration may be in unit dose form, and may contain conventional excipients, such as binding agents, fillers, tabletting lubricants, disintegrants and acceptable wetting agents.
  • the tablets may be coated according to methods well known in normal pharmaceutical practice.
  • Oral liquid preparations may be in the form of, for example, aqueous or oily suspension, solutions, emulsions, syrups or elixirs, or may be in the form of 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, if desired, conventional flavourings or colorants.
  • fluid unit dosage forms are prepared utilising a compound of the invention or pharmaceutically acceptable salt thereof and a sterile vehicle.
  • the compound depending on the vehicle and concentration used, can be either suspended or dissolved in the vehicle.
  • the compound can be dissolved for injection and filter sterilised before filling into a suitable vial or ampoule and sealing.
  • adjuvants such as a local anaesthetic, preservatives and buffering agents are 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 sterilisation cannot be accomplished by filtration.
  • the compound can be sterilised by exposure to ethylene oxide before suspension in a sterile vehicle.
  • a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound.
  • composition may contain from 0.1% to 99% by weight, preferably from 10 to 60% by weight, of the active material, depending on the method of administration.
  • suitable unit doses may be 0.05 to 1000 mg, more suitably 1.0 to 200 mg, and such unit doses may be administered more than once a day, for example two or three a day. Such therapy may extend for a number of weeks or months. When administered in accordance with the invention, no unacceptable toxicological effects are expected with the compounds of the invention.
  • Benzodioxan-5-carboxylic acid (prepared as described by E.A.Watts, in Azabicycloalkylbenzamides and pharmaceutical compositions containing them, EP 82-303057 June 1982) (15 g) was dissolved in a mixture of glacial acetic acid (67 ml) and acetic anhydride (67 ml). The solution was heated to 40° C and treated with a solution of fuming nitric acid (13 ml) in acetic acid (13 ml) at a rate such that the temperature was maintained at 45-50° C with occasional ice/water cooling. The mixture was stirred at 50°-53° C for 2 days, then cooled and filtered to give the title compound as a white powder (4.09 g, 22%).
  • the mixture was refluxed for 3h, cooled and filtered through a short neutral alumina column eluting widi dichloromethane, tiien ethyl acetate.
  • the solvent was evaporated under reduced pressure, and the residual carbamate dissolved in methanol (10 ml) and stood overnight The solvent was evaporated under reduced pressure to leave the tide compound as a white powder (38 mg, 22%) Mp 175-180° C.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Dérivés d'amides représentés par la formule (I) ou sel desdits dérivés, dans laquelle R1 représente halogène, cyclaolkyle C¿3-6?, phényle éventuellement substitué ou un noyau hétérocyclique à 5-7 constituants éventuellement substitué et contenant de 1 à 3 hétéroatomes sélectionnés à partir d'oxygène, azote ou soufre; R?2¿ représente hydrogène, halogène, alkyle C¿1-6? alkoxy C1-6, acyle, nitro, trifluorométhyle ou cyano; R?3¿ représente hydrogène ou alkyle C¿1-6?; A représente -(CR?4R5)¿m- ou -O(CR4R5)n- oú R4 et R5 représentent indépendamment hydrogène ou alkyle C¿1-6?, m est 2 ou 3; n est 1, 2 ou 3 et B représente CONH ou NHCO. L'invention concerne également des procédés de préparation desdits dérivés, ainsi que des compositions pharmaceutiques contenant lesdits dérivés.
EP94930171A 1993-10-19 1994-10-13 Derives de benzanilide en tant qu'antagonistes du recepteur de 5ht-1d Withdrawn EP0724580A1 (fr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
GB939321490A GB9321490D0 (en) 1993-10-19 1993-10-19 Novel compounds
GB9321490 1993-10-19
GB939325866A GB9325866D0 (en) 1993-12-17 1993-12-17 Novel compounds
GB9325866 1993-12-17
PCT/EP1994/003387 WO1995011243A1 (fr) 1993-10-19 1994-10-13 Derives de benzanilide en tant qu'antagonistes du recepteur de 5ht-1d

Publications (1)

Publication Number Publication Date
EP0724580A1 true EP0724580A1 (fr) 1996-08-07

Family

ID=26303698

Family Applications (1)

Application Number Title Priority Date Filing Date
EP94930171A Withdrawn EP0724580A1 (fr) 1993-10-19 1994-10-13 Derives de benzanilide en tant qu'antagonistes du recepteur de 5ht-1d

Country Status (3)

Country Link
EP (1) EP0724580A1 (fr)
JP (1) JPH09503773A (fr)
WO (1) WO1995011243A1 (fr)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9519033D0 (en) * 1995-09-18 1995-11-15 Smithkline Beecham Plc Treatment
SE9601110D0 (sv) 1996-03-22 1996-03-22 Astra Ab Substituted 1,2,3,4-tetrahydronaphthalene derivatives
WO1998027058A2 (fr) * 1996-12-19 1998-06-25 Smithkline Beecham Plc Nouveaux composes
DZ2376A1 (fr) * 1996-12-19 2002-12-28 Smithkline Beecham Plc Dérivés de sulfonamides nouveaux procédé pour leurpréparation et compositions pharmaceutiques les c ontenant.
SE9900190D0 (sv) 1999-01-22 1999-01-22 Astra Ab New compounds
SE9702799D0 (sv) 1997-07-25 1997-07-25 Astra Ab New compounds
EP1204658B1 (fr) * 1999-07-29 2003-05-07 Eli Lilly And Company Agonistes de la serotonine benzofurylpiperazine
PT1204654E (pt) 1999-07-29 2003-11-28 Lilly Co Eli Benzofurilpiperazinas agonistas do receptor 5-ht2c da serotonina
PE20020506A1 (es) 2000-08-22 2002-07-09 Glaxo Group Ltd Derivados de pirazol fusionados como inhibidores de la proteina cinasa
US6858592B2 (en) 2001-06-29 2005-02-22 Genzyme Corporation Aryl boronic acids for treating obesity
US7041280B2 (en) 2001-06-29 2006-05-09 Genzyme Corporation Aryl boronate functionalized polymers for treating obesity
US7504395B2 (en) 2001-07-20 2009-03-17 Psychogenics, Inc. Treatment for attention-deficit hyperactivity disorder
GB0124934D0 (en) 2001-10-17 2001-12-05 Glaxo Group Ltd Chemical compounds
GB0124941D0 (en) 2001-10-17 2001-12-05 Glaxo Group Ltd Chemical compounds
GB0124931D0 (en) 2001-10-17 2001-12-05 Glaxo Group Ltd Chemical compounds
GB0124939D0 (en) 2001-10-17 2001-12-05 Glaxo Group Ltd Chemical compounds
GB0124936D0 (en) 2001-10-17 2001-12-05 Glaxo Group Ltd Chemical compounds
GB0124933D0 (en) 2001-10-17 2001-12-05 Glaxo Group Ltd Chemical compounds
GB0124938D0 (en) 2001-10-17 2001-12-05 Glaxo Group Ltd Chemical compounds
EP1474395B1 (fr) 2002-02-12 2007-10-17 Smithkline Beecham Corporation Derives de nicotinamide utiles comme inhibiteurs de p38
GB0217757D0 (en) 2002-07-31 2002-09-11 Glaxo Group Ltd Novel compounds
GB0308185D0 (en) 2003-04-09 2003-05-14 Smithkline Beecham Corp Novel compounds
GB0308201D0 (en) 2003-04-09 2003-05-14 Smithkline Beecham Corp Novel compounds
GB0308186D0 (en) 2003-04-09 2003-05-14 Smithkline Beecham Corp Novel compounds
GB0318814D0 (en) 2003-08-11 2003-09-10 Smithkline Beecham Corp Novel compounds
WO2006062481A1 (fr) * 2004-12-09 2006-06-15 Biovitrum Ab Nouveaux derives de benzofurane et leur utilisation dans le traitement de l'obesite, du diabete de type 2 et des troubles du systeme nerveux central
CN103896831A (zh) * 2007-08-27 2014-07-02 Abbvie德国有限责任两合公司 4-(4-吡啶基)-苯甲酰胺及其作为rock活性调节剂的应用
GB201002563D0 (en) 2010-02-15 2010-03-31 Cambridge Entpr Ltd Compounds
ES2838573T3 (es) * 2014-08-21 2021-07-02 Bristol Myers Squibb Co Derivados de benzamida ligados como inhibidores potentes de ROCK
US11498903B2 (en) 2017-08-17 2022-11-15 Bristol-Myers Squibb Company 2-(1,1′-biphenyl)-1H-benzodimidazole derivatives and related compounds as apelin and APJ agonists for treating cardiovascular diseases
WO2020183011A1 (fr) 2019-03-14 2020-09-17 Institut Curie Inhibiteurs de htr1d et leurs utilisations dans le traitement du cancer

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Publication number Priority date Publication date Assignee Title
GB9119920D0 (en) * 1991-09-18 1991-10-30 Glaxo Group Ltd Chemical compounds
ATE204262T1 (de) * 1991-09-18 2001-09-15 Glaxo Group Ltd Benzanilidderivate als 5-ht1d-antagonisten
GB9119932D0 (en) * 1991-09-18 1991-10-30 Glaxo Group Ltd Chemical compounds

Non-Patent Citations (1)

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Title
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Also Published As

Publication number Publication date
WO1995011243A1 (fr) 1995-04-27
JPH09503773A (ja) 1997-04-15

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