WO1998035947A1 - Derives de 4-aminoalcoxy-1,3-dihydrobenzoimidazol-2-thiones, leur preparation et leur utilisation en tant qu'agonistes d'autorecepteur de la dopamine (d2) - Google Patents

Derives de 4-aminoalcoxy-1,3-dihydrobenzoimidazol-2-thiones, leur preparation et leur utilisation en tant qu'agonistes d'autorecepteur de la dopamine (d2) Download PDF

Info

Publication number
WO1998035947A1
WO1998035947A1 PCT/US1998/000612 US9800612W WO9835947A1 WO 1998035947 A1 WO1998035947 A1 WO 1998035947A1 US 9800612 W US9800612 W US 9800612W WO 9835947 A1 WO9835947 A1 WO 9835947A1
Authority
WO
WIPO (PCT)
Prior art keywords
dihydro
ethoxy
pharmaceutically acceptable
acceptable salt
alkyl
Prior art date
Application number
PCT/US1998/000612
Other languages
English (en)
Inventor
James Albert Nelson
Richard Eric Mewshaw
Uresh Shantilal Shah
Original Assignee
American Home Products Corporation
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 American Home Products Corporation filed Critical American Home Products Corporation
Priority to HU0001942A priority Critical patent/HUP0001942A2/hu
Priority to JP53572698A priority patent/JP2001511803A/ja
Priority to CA002278718A priority patent/CA2278718A1/fr
Priority to EP98902512A priority patent/EP0964854A1/fr
Priority to BR9807840-2A priority patent/BR9807840A/pt
Priority to IL13115798A priority patent/IL131157A0/xx
Priority to AU59152/98A priority patent/AU5915298A/en
Publication of WO1998035947A1 publication Critical patent/WO1998035947A1/fr

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
    • C07D401/12—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 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
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C07D235/28—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N19/00—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
    • H04N19/10—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding
    • H04N19/102—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding characterised by the element, parameter or selection affected or controlled by the adaptive coding
    • H04N19/124—Quantisation
    • H04N19/126—Details of normalisation or weighting functions, e.g. normalisation matrices or variable uniform quantisers
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N19/00—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
    • H04N19/10—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding
    • H04N19/134—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding characterised by the element, parameter or criterion affecting or controlling the adaptive coding
    • H04N19/154—Measured or subjectively estimated visual quality after decoding, e.g. measurement of distortion
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N19/00—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
    • H04N19/10—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding
    • H04N19/169—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding characterised by the coding unit, i.e. the structural portion or semantic portion of the video signal being the object or the subject of the adaptive coding
    • H04N19/17—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding characterised by the coding unit, i.e. the structural portion or semantic portion of the video signal being the object or the subject of the adaptive coding the unit being an image region, e.g. an object
    • H04N19/172—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding characterised by the coding unit, i.e. the structural portion or semantic portion of the video signal being the object or the subject of the adaptive coding the unit being an image region, e.g. an object the region being a picture, frame or field
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N19/00—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
    • H04N19/10—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding
    • H04N19/169—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding characterised by the coding unit, i.e. the structural portion or semantic portion of the video signal being the object or the subject of the adaptive coding
    • H04N19/182—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding characterised by the coding unit, i.e. the structural portion or semantic portion of the video signal being the object or the subject of the adaptive coding the unit being a pixel
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N19/00—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
    • H04N19/60—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using transform coding
    • H04N19/61—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using transform coding in combination with predictive coding
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N19/00—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
    • H04N19/85—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using pre-processing or post-processing specially adapted for video compression
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N19/00—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
    • H04N19/10—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding
    • H04N19/102—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding characterised by the element, parameter or selection affected or controlled by the adaptive coding
    • H04N19/124—Quantisation
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N19/00—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
    • H04N19/10—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding
    • H04N19/102—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding characterised by the element, parameter or selection affected or controlled by the adaptive coding
    • H04N19/132—Sampling, masking or truncation of coding units, e.g. adaptive resampling, frame skipping, frame interpolation or high-frequency transform coefficient masking
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N19/00—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
    • H04N19/10—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding
    • H04N19/134—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding characterised by the element, parameter or criterion affecting or controlling the adaptive coding
    • H04N19/146—Data rate or code amount at the encoder output
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N19/00—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
    • H04N19/10—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding
    • H04N19/134—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding characterised by the element, parameter or criterion affecting or controlling the adaptive coding
    • H04N19/146—Data rate or code amount at the encoder output
    • H04N19/149—Data rate or code amount at the encoder output by estimating the code amount by means of a model, e.g. mathematical model or statistical model
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N19/00—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
    • H04N19/10—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding
    • H04N19/134—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding characterised by the element, parameter or criterion affecting or controlling the adaptive coding
    • H04N19/146—Data rate or code amount at the encoder output
    • H04N19/15—Data rate or code amount at the encoder output by monitoring actual compressed data size at the memory before deciding storage at the transmission buffer
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N19/00—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
    • H04N19/10—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding
    • H04N19/134—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using adaptive coding characterised by the element, parameter or criterion affecting or controlling the adaptive coding
    • H04N19/146—Data rate or code amount at the encoder output
    • H04N19/152—Data rate or code amount at the encoder output by measuring the fullness of the transmission buffer
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N19/00—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals
    • H04N19/60—Methods or arrangements for coding, decoding, compressing or decompressing digital video signals using transform coding

Definitions

  • This invention relates to a novel series of compounds having potency at the dopamine D 2 receptor which are illustrated by the following Formula I:
  • Intrinsic activity is predicted using the ratio of the "low-affinity agonist" (LowAg) state of the receptor and the "high-affinity agonist” (HighAg) state of the receptor, i.e. LowAg HighAg. These ratios correlate with the agonist, partial agonist, and antagonist activities of a given compound, which activities characterize a compounds ability to elicit an antipsychotic effect.
  • EPS extrapyramidal side effects
  • the compounds of this invention are dopamine agonists with various degrees of intrinsic activity some of which are selective autoreceptor agonists, and therefore partial agonist (i.e. activate only autoreceptors versus postsynaptic D 2 dopamine receptors).
  • partial agonist i.e. activate only autoreceptors versus postsynaptic D 2 dopamine receptors.
  • they provide functional modulation of the dopamine systems of the brain without the excessive blockade of the postsynaptic dopamine receptors which have been observed to be responsible for the serious side effects frequently exhibited by agents found otherwise clinically effective for the treatment of schizophrenia.
  • dopamine autoreceptors results in reduced neuronal firing a well as inhibition of dopamine synthesis and release and therefore provide a means of controlling hyperactivity of the dopaminergic systems.
  • the compounds of this invention were also found to have high intrinsic activity and therefore they can behave as the natural neurotransmitter, i.e., as full agonists. As such, they are useful in the treatment of diseases having abnormal concentrations of dopamine and could be used as dopamine surrogates possibly in the treatment of Parkinson's disease.
  • CGP-12177 (Ciba Geigy, shown below) was found to be a ⁇ -adrenergic receptor antagonist [J. Biol. Chem., 258, 3496- 3502, 1983].
  • the compounds of this invention are 4-aminoethoxy-l,3-dihydro-benzoimidazol-
  • R 1 is hydrogen or C ⁇ -C 6 alkyl
  • R 2 is hydrogen or Ci-C ⁇ alkyl
  • R 3 is selected from hydrogen, straight-chain and branched alkyl group having up to 10 carbon atoms, cyclohexylmethyl or
  • -CEL mAr where Ar is phenyl, naphthyl, thienyl, furanyl or pyridinyl, each optionally substituted by one or two substituents selected independently from -C 6 alkyl, halogen, -Cg alkoxide and trifluoromethyl; or NR 2 R 3 is 1, 2, 3, 4-tetrahydroquinolin-l-yl or 1, 2, 3, 4- tetrahydroisoquinolin-2-yl; m is 1-5; n is 1 or 2;
  • Y is halogen, C,-C 6 alkyl, and - alkoxy; and the pharmaceutically acceptable salts thereof.
  • Pharmaceutically acceptable acid addition salts have the utility of the free base.
  • Such salts are prepared by methods well known to the art are formed with both inorganic or organic acids including but not Umited to fumaric, maleic, benzoic, ascorbic, pamoic, succinic, bismethylenesalicylic, methanesulfonic, ethanedisulfonic, acetic, oxalic, propionic, tartaric, salicyclic, citric, gluconic, lactic, malic, mandelic, cinnamic, citraconic, aspartic, stearic, palmitic, itaconic, glycolic, p-aminobenzoic, glutamic, benzene-sulfonic, hydrochloric hydrobromic, sulfuric, cyclohexylsulfamic, phosphoric and nitric acids.
  • inorganic or organic acids including but not Umited to fumaric, maleic, benzoic, ascorbic, pamoic, succinic, bismethylenesalicylic
  • Scheme I depicts the synthesis of invention compounds where one of R 1 or R2 is hydrogen.
  • Scheme HI illustrates a route for obtaining a chlorinated intermediate which is used in the synthesis of a chlorinated invention compound.
  • the hydrochloride salt of the title compound was prepared as a white solid (90.0 %), mp >250 °C; M mle (+)FAB 340 (M+H)+.
  • the hydrochloride salt of the title compound was prepared as a white solid (90.0 %), mp >250 °C; MS mle (+)FAB 340 (M+H)+.
  • the compounds of this invention are dopamine autoreceptor agonists, that is, they serve to modulate the synthesis and release of the neurotransmitter dopamine. They are thus useful for treatment of disorders of the dopaminergic system, such as schizophrenia, Parkinson's disease and Tourette's syndrome. Such agents are partial agonists at the postsynaptic dopamine D 2 receptor and are thereby useful in the treatment of alcohol and drug addiction.
  • the compounds of this invention effect the synthesis of the neurotransmitter dopamine and thus are useful in the treatment of dopaminergic disorders such as schizophrenia, Parkinson's disease, Tourette's Syndrome, alcohol addiction, cocaine addiction, and addiction to analagous drugs.
  • Applicable solid carriers for pharmaceutical compositions containing the compounds of this invention can include one or more substances which may also act as flavoring agents, lubricants, solubilizers, suspending agents, fillers, glidants, compression aids, binders or tablet-disintergrating agents or an encapsulating material.
  • the carrier is a finely divided solid which is in admixture with the finely divided active ingredient.
  • the active ingredient is mixed with a carrier having the necessary compression properties in suitable proportions and compacted in the shape and size desired.
  • the powders and tablets preferably contain up to 99% of the active ingredient.
  • Suitable solid carriers include, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidine, low melting waxes and ion exchange resins.
  • Liquid carriers may be used in preparing solutions, suspensions, emulsions, syrups and elixirs.
  • the active ingredient of this invention can be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fat.
  • the liquid carrier can contain other suitable pharmaceutical additives such as solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending agents, thickening agents, colors, viscosity regulators, stabilizers or osmo-regulators.
  • suitable examples of liquid carriers for oral and parenteral administration include water (particularly containing additives as above e.g.
  • cellulose derivatives preferably sodium carboxymethyl cellulose solution
  • alcohols including monohydric alcohols and polyhydric alcohols e.g. glycols
  • oils e.g. fractionated coconut oil and arachis oil
  • the carrier can also be an oily ester such as ethyl oleate and isopropyl myristate.
  • Sterile liquid carriers are used in sterile liquid form compositions for parenteral administration.
  • Liquid pharmaceutical compositions which are sterile solutions or suspensions can be utilized by, for example, intramuscular, intraperitoneal or subcutaneous injection. Sterile solutions can also be administered intravenously. Oral administration may be either liquid or solid composition form.
  • the pharmaceutical composition is in unit dosage form, e.g. as tablets or capsules.
  • the composition is sub-divided in unit dose containing appropriate quantities of the active ingredient;
  • the unit dosage forms can be packaged compositions, for example packeted powders, vials, ampoules, prefilled syringes or sachets containing liquids.
  • the unit dosage form can be, for example, a capsule or tablet itself, or it can be the appropriate number of any such compositions in package form.
  • the dosage to be used in the treatment of a specific psychosis must be subjectively determined by the attending physician.
  • the variables involved include the specific psychosis and the size, age and response pattern of the patient.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Signal Processing (AREA)
  • Multimedia (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Psychiatry (AREA)
  • Psychology (AREA)
  • Addiction (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une nouvelle série de composés présentant une activité au niveau du récepteur de la dopamine D2, qui sont illustrés par la formule (I), ou bien un sel pharmaceutiquement acceptable de ceux-ci. Dans cette formule, R1 est hydrogène ou alkyle C¿1?-C6; R?2¿ est hydrogène ou alkyle C¿1?-C6; R?3¿ est choisi parmi hydrogène, un groupe alkyle à chaîne droite et ramifié possédant jusqu'à dix atomes de carbone, cyclohexylméthyle ou bien -(CH¿2?)mAr où Ar est phényle, naphtyle, thiényle, furanyle ou pyridinyle, éventuellement substitués par un ou deux substituants choisis indépendamment parmi alkyle C1-C6, halogène, alcoxy C1-C6 et trifluorométhyle; ou bien NR?2R3¿ est 1,2,3,4-tétrahydroquinoléin-1-yle ou 1,2,3,4-tétrahydroisoquinoléin-2-yle; m vaut 1-5; n vaut 1 ou 2; Y est halogène, alcyle C¿1?-C6 et alcoxy C1-C6.
PCT/US1998/000612 1997-02-18 1998-01-13 Derives de 4-aminoalcoxy-1,3-dihydrobenzoimidazol-2-thiones, leur preparation et leur utilisation en tant qu'agonistes d'autorecepteur de la dopamine (d2) WO1998035947A1 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
HU0001942A HUP0001942A2 (hu) 1997-02-18 1998-01-13 4-Amino-alkoxi-1,3-dihidro-benzimidazol-2-tion-származékok, alkalmazásuk és az ezeket tartalmazó gyógyszerkészítmények
JP53572698A JP2001511803A (ja) 1997-02-18 1998-01-13 ４−アミノアルコキシ−１，３−ジヒドロベンゾイミダゾール−２−チオン誘導体、それらの調製およびそれらのドパミン自己受容体（ｄ▲下２▼）作動薬としての使用
CA002278718A CA2278718A1 (fr) 1997-02-18 1998-01-13 Derives de 4-aminoalcoxy-1,3-dihydrobenzoimidazol-2-thiones, leur preparation et leur utilisation en tant qu'agonistes d'autorecepteur de la dopamine (d2)
EP98902512A EP0964854A1 (fr) 1997-02-18 1998-01-13 Derives de 4-aminoalcoxy-1,3-dihydrobenzoimidazol-2-thiones, leur preparation et leur utilisation en tant qu'agonistes d'autorecepteur de la dopamine (d2)
BR9807840-2A BR9807840A (pt) 1997-02-18 1998-01-13 Derivados de 4-aminoalcóxi-1,3-dihidrobenzoimidazol-2-tionas, sua preparação e seu uso como agonistas de auto-receptor de dopamina (d2)
IL13115798A IL131157A0 (en) 1997-02-18 1998-01-13 4-Aminoalkoxy-1,3-dihydrobenzoimidazol-2-thione derivatives their preparation and their use as dopamine autoreceptor (d2) agonists
AU59152/98A AU5915298A (en) 1997-02-18 1998-01-13 4-aminoalkoxy-1,3-dihydrobenzoimidazol-2-thiones derivatives, their preparation and their use as dopamine autoreceptor (d2) agonists

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US80265197A 1997-02-18 1997-02-18
US08/802,651 1997-02-18

Publications (1)

Publication Number Publication Date
WO1998035947A1 true WO1998035947A1 (fr) 1998-08-20

Family

ID=25184324

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/000612 WO1998035947A1 (fr) 1997-02-18 1998-01-13 Derives de 4-aminoalcoxy-1,3-dihydrobenzoimidazol-2-thiones, leur preparation et leur utilisation en tant qu'agonistes d'autorecepteur de la dopamine (d2)

Country Status (12)

Country Link
EP (1) EP0964854A1 (fr)
JP (1) JP2001511803A (fr)
KR (1) KR20000071124A (fr)
CN (1) CN1252061A (fr)
AR (1) AR011139A1 (fr)
AU (1) AU5915298A (fr)
BR (1) BR9807840A (fr)
CA (1) CA2278718A1 (fr)
HU (1) HUP0001942A2 (fr)
IL (1) IL131157A0 (fr)
WO (1) WO1998035947A1 (fr)
ZA (1) ZA981308B (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1986001204A1 (fr) * 1984-08-15 1986-02-27 Schering Aktiengesellschaft Nouveaux derives de dopamine, procede pour leur production et leur utilisation comme produits medicinaux
EP0707007A1 (fr) * 1994-10-14 1996-04-17 MERCK PATENT GmbH Dérivés d'amino(thio)éther agissant sur le système nerveux central
WO1997023216A1 (fr) * 1995-12-22 1997-07-03 Warner-Lambert Company Analogues de piperidine a substitution en position 4 et utilisation de ces derniers en tant qu'antagonistes selectivement actifs contre les sous-types du recepteur de nmda

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1986001204A1 (fr) * 1984-08-15 1986-02-27 Schering Aktiengesellschaft Nouveaux derives de dopamine, procede pour leur production et leur utilisation comme produits medicinaux
EP0707007A1 (fr) * 1994-10-14 1996-04-17 MERCK PATENT GmbH Dérivés d'amino(thio)éther agissant sur le système nerveux central
WO1997023216A1 (fr) * 1995-12-22 1997-07-03 Warner-Lambert Company Analogues de piperidine a substitution en position 4 et utilisation de ces derniers en tant qu'antagonistes selectivement actifs contre les sous-types du recepteur de nmda

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
JAEN J.C. ET AL.: "Dopamine autoreceptor agonists as potential antipsychotics. 1. (Aminoalkoxy)anilines", JOURNAL OF MEDICINAL CHEMISTRY, vol. 31, no. 8, August 1988 (1988-08-01), pages 1621 - 1625, XP000674393 *

Also Published As

Publication number Publication date
IL131157A0 (en) 2001-01-28
CN1252061A (zh) 2000-05-03
KR20000071124A (ko) 2000-11-25
ZA981308B (en) 1999-08-17
AU5915298A (en) 1998-09-08
EP0964854A1 (fr) 1999-12-22
AR011139A1 (es) 2000-08-02
BR9807840A (pt) 2000-09-19
HUP0001942A2 (hu) 2000-11-28
JP2001511803A (ja) 2001-08-14
CA2278718A1 (fr) 1998-08-20

Similar Documents

Publication Publication Date Title
WO2011061318A1 (fr) Composés hétérocyliques en tant qu'antagonistes des récepteurs d'orexine
WO2006018308A1 (fr) Antagonistes du recepteur 5-ht7
US5972958A (en) 4-aminoalkoxy-1,3-dihydro-benzoimidazol-2-thiones
US6127380A (en) 4-aminoalkoxy-1H-benzoimidazoles
EP0964854A1 (fr) Derives de 4-aminoalcoxy-1,3-dihydrobenzoimidazol-2-thiones, leur preparation et leur utilisation en tant qu'agonistes d'autorecepteur de la dopamine (d2)
EP1630159A1 (fr) Antagonistes des recepteurs 5-HT7
US5990144A (en) 4-aminoalkoxy-1,3-dihydrobenzoimidazol-2-one dopamine autoreceptor agonists
EP0973749A1 (fr) Derives de 4-aminoalcoxy-1h-benzimidazole, leur preparation et leur utilisation comme agonistes des autorecepteurs de la dopamine (d 2?)
US5756521A (en) Chroman-2-ylmethylamino derivatives
AU722616B2 (en) 5-aminoalkoxy-1,4-dihydroquinoxaline-2,3-diones being dopamine agonists
MXPA99007587A (en) 4-aminoalkoxy-1,3-dihydrobenzoimidazol-2-thiones derivatives, their preparation and their use as dopamine autoreceptor (d2) agonists
US5922715A (en) 5-aminoalkoxy-1, 4-dihydroquinoxaline-2, 3-diones
AU744443B2 (en) 4-aminoalkoxy-1,3-dihydrobenzoimidazol-2-one derivatives, their preparation and their use as dopamine autoreceptor (D2) agonists
MXPA99007586A (en) 4-aminoalkoxy-1h-benzimidazole derivatives, their preparation and their use as dopamine autoreceptor (d2
EP0923576B1 (fr) Derives de 4-aminoethoxy-indolone utilises en tant qu'agonistes du recepteur d2 de la dopamine
EP1073636A1 (fr) 4-amino-(ethylamino)-oxindoles utilises comme agonistes des autorecepteurs de la dopamine
US5872144A (en) 4-aminoethoxyindazole derivatives
MXPA99007585A (en) 4-aminoalkoxy-1,3-dihydrobenzoimidazol-2-one derivatives, theirpreparation and their use as dopamine autoreceptor (d2) agonists
MXPA99007593A (en) 5-aminoalkoxy-1,4-dihydroquinoxaline-2,3-diones being dopamine agonists
WO1998035942A1 (fr) Derives de 4-aminoethoxyindazole
MXPA01006351A (en) Diphenylurea compounds

Legal Events

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

Ref document number: 131157

Country of ref document: IL

Ref document number: 98804120.0

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 GH 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 SL TJ TM TR TT UA UG UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SZ UG ZW 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

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

Ref document number: 2278718

Country of ref document: CA

Ref document number: 2278718

Country of ref document: CA

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 1998 535726

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 1998902512

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 337270

Country of ref document: NZ

Ref document number: 59152/98

Country of ref document: AU

Ref document number: 1019997007412

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: PA/a/1999/007587

Country of ref document: MX

WWP Wipo information: published in national office

Ref document number: 1998902512

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWP Wipo information: published in national office

Ref document number: 1019997007412

Country of ref document: KR

WWW Wipo information: withdrawn in national office

Ref document number: 1998902512

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1019997007412

Country of ref document: KR