[go: up one dir, main page]

WO1998035943A1 - Derives du 4-aminoethoxyindazole - Google Patents

Derives du 4-aminoethoxyindazole Download PDF

Info

Publication number
WO1998035943A1
WO1998035943A1 PCT/US1998/002413 US9802413W WO9835943A1 WO 1998035943 A1 WO1998035943 A1 WO 1998035943A1 US 9802413 W US9802413 W US 9802413W WO 9835943 A1 WO9835943 A1 WO 9835943A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutically acceptable
alkoxy
halogen
phenyl
alkyl
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/US1998/002413
Other languages
English (en)
Inventor
Richard Eric Mewshaw
Anthonie Johan Verwijs
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.)
Wyeth LLC
Original Assignee
American Home Products Corp
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 Corp filed Critical American Home Products Corp
Priority to JP53584198A priority Critical patent/JP2001512458A/ja
Priority to AU62733/98A priority patent/AU6273398A/en
Priority to IL13115998A priority patent/IL131159A0/xx
Priority to CA002278746A priority patent/CA2278746A1/fr
Priority to BR9807397-4A priority patent/BR9807397A/pt
Priority to EP98905000A priority patent/EP0960101A1/fr
Publication of WO1998035943A1 publication Critical patent/WO1998035943A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
    • C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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

Definitions

  • This invention relates to 4-aminoethoxyindazole derivatives having dopamine D agonist activity useful for antipsychotic effects and antiparkinsonism.
  • 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.
  • the compounds of this invention are dopamine agonists 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).
  • the compounds of this invention are essentially free from extrapyramidal side effects (EPS).
  • the compounds of this invention are 4-aminoethoxy-benzimidazole derivatives which are illustrated by Formula I below.
  • Y is hydrogen, halogen, or -C 6 alkoxy
  • R 1 is hydrogen or C ⁇ -C 6 alkyl
  • X is methylene, oxygen or carbonyl
  • the compounds of this Formula I also may be used in the form of a pharmaceutically acceptable acid addition salt having the utility of the free base.
  • Such salts prepared by methods well known to the art are formed with both inorganic or organic acids, for example: 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.
  • the compounds of Formula I are generally prepared by the overall sequence indicated in Scheme
  • 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.
  • Affinity for the dopamine autoreceptor was established by a modification of the standard experimental test procedure of Seemen and Schaus, European Journal of Pharmacology 203, 105-109, 1991, wherein homogenized rat striatal brain tissue is incubated with ⁇ H-quinpirole (Quin.) and various concentrations of test compound, filtered and washed and counted in a Betaplate scintillation counter.
  • 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 analogous 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-disintegrating 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 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) and their derivatives, and oils (e.g. fractionated coconut oil and arachis oil).
  • the carrier can also be an oily ester such as ethyl ole
  • 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

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

Abstract

L'invention porte sur des agonistes de la dopamine D2, de formule (I) dans laquelle: Y est H, halogène, ou C1-C6 alkoxy; R1 est H ou C¿1?-C6 alkyle; X est méthylène, O ou carbonyle; Ar est phényle ou triényle, chacun d'eux étant facultativement substitué par des groupes 1-2 choisis indépendamment parmi C1-C6 alkoxy, C1-C6 alkyle, halogène, trifluorométhyle et phényle; n est 0-4, ou sur leurs sels pharmacocompatibles. Les agonistes de la dopamine D2 peuvent être utilisés dans le traitement de la schizophrénie, du syndrome de Tourette, de la toxicomanie ou de l'alcoolisme, et également dans celui de la maladie de Parkinson.
PCT/US1998/002413 1997-02-18 1998-02-13 Derives du 4-aminoethoxyindazole Ceased WO1998035943A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
JP53584198A JP2001512458A (ja) 1997-02-18 1998-02-13 ４−アミノエトキシインダゾール誘導体
AU62733/98A AU6273398A (en) 1997-02-18 1998-02-13 4-aminoethoxyindazole derivatives
IL13115998A IL131159A0 (en) 1997-02-18 1998-02-13 4-Aminoethoxyindazole derivatives
CA002278746A CA2278746A1 (fr) 1997-02-18 1998-02-13 Derives du 4-aminoethoxyindazole
BR9807397-4A BR9807397A (pt) 1997-02-18 1998-02-13 Derivados 4-aminoetoxiindazol
EP98905000A EP0960101A1 (fr) 1997-02-18 1998-02-13 Derives du 4-aminoethoxyindazole

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US80132597A 1997-02-18 1997-02-18
US08/801,325 1997-02-18

Publications (1)

Publication Number Publication Date
WO1998035943A1 true WO1998035943A1 (fr) 1998-08-20

Family

ID=25180801

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/US1998/001167 Ceased WO1998035942A1 (fr) 1997-02-18 1998-01-13 Derives de 4-aminoethoxyindazole
PCT/US1998/002413 Ceased WO1998035943A1 (fr) 1997-02-18 1998-02-13 Derives du 4-aminoethoxyindazole

Family Applications Before (1)

Application Number Title Priority Date Filing Date
PCT/US1998/001167 Ceased WO1998035942A1 (fr) 1997-02-18 1998-01-13 Derives de 4-aminoethoxyindazole

Country Status (11)

Country Link
EP (1) EP0960101A1 (fr)
JP (1) JP2001512458A (fr)
KR (1) KR20000071125A (fr)
CN (1) CN1248246A (fr)
AR (1) AR011137A1 (fr)
AU (2) AU6246198A (fr)
BR (1) BR9807397A (fr)
CA (1) CA2278746A1 (fr)
IL (1) IL131159A0 (fr)
WO (2) WO1998035942A1 (fr)
ZA (1) ZA981307B (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016071293A3 (fr) * 2014-11-03 2016-08-25 Iomet Pharma Ltd Composé pharmaceutique

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA200601985A1 (ru) * 2004-05-26 2007-04-27 Пфайзер Лимитед Новые производные индазола и индолона и их применение в качестве фармацевтических средств

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994021626A1 (fr) * 1993-03-18 1994-09-29 Merck Sharp & Dohme Limited Derives d'indazole
WO1994021630A1 (fr) * 1993-03-18 1994-09-29 Merck Sharp & Dohme Limited Derives d'indazole a action neuroleptique

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994021626A1 (fr) * 1993-03-18 1994-09-29 Merck Sharp & Dohme Limited Derives d'indazole
WO1994021630A1 (fr) * 1993-03-18 1994-09-29 Merck Sharp & Dohme Limited Derives d'indazole a action neuroleptique

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 114, no. 3, 21 January 1991, Columbus, Ohio, US; abstract no. 23858x, MOSTI LUISA ET AL.: "4-substituted 1-phenyl-1H-indazoles with analgetic, antinflammatory, antipyretic and local anesthetic activities." page 697; column 2; XP002063971 *
CHEMICAL ABSTRACTS, vol. 117, no. 23, 7 December 1992, Columbus, Ohio, US; abstract no. 225909n, MOSTI LUISA ET AL.: "4-substituted 1-methyl-1-H-indazoles with analgesic, antiinflammatory and antipyretic activities" page 36; column 2; XP002063970 *
FARMACO, vol. 45, no. 4, 1990, pages 415 - 429 *
FARMACO, vol. 47, no. 5, 1992, pages 567 - 584 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016071293A3 (fr) * 2014-11-03 2016-08-25 Iomet Pharma Ltd Composé pharmaceutique
US10590086B2 (en) 2014-11-03 2020-03-17 Iomet Pharma Ltd. Pharmaceutical compound
RU2719446C2 (ru) * 2014-11-03 2020-04-17 Айомет Фарма Лтд Фармацевтическое соединение
US11130738B2 (en) 2014-11-03 2021-09-28 Iomet Pharma Ltd. Pharmaceutical compound

Also Published As

Publication number Publication date
KR20000071125A (ko) 2000-11-25
AU6246198A (en) 1998-09-08
WO1998035942A1 (fr) 1998-08-20
BR9807397A (pt) 2000-03-14
CN1248246A (zh) 2000-03-22
AR011137A1 (es) 2000-08-02
JP2001512458A (ja) 2001-08-21
CA2278746A1 (fr) 1998-08-20
EP0960101A1 (fr) 1999-12-01
ZA981307B (en) 1999-08-17
IL131159A0 (en) 2001-01-28
AU6273398A (en) 1998-09-08

Similar Documents

Publication Publication Date Title
US5885988A (en) Benzo g!quinoline derivatives
US5663194A (en) Chroman-2-ylmethylamino derivatives
US5750556A (en) 2-(aminomethyl)-3,4,7,9-tetrahydro-2H-pyrano- 2,3-E!indol-8-ones and derivatives
EP0771801B1 (fr) Dérivés de chromanne
US5872144A (en) 4-aminoethoxyindazole derivatives
WO1998035943A1 (fr) Derives du 4-aminoethoxyindazole
US5096900A (en) (4-piperidyl)methyl-2,3-dihydro-1h-isoindole and -2,3,4,5-tetrahydro-1h-benzazepine derivatives, their preparation and their application in therapy
US5756521A (en) Chroman-2-ylmethylamino derivatives
US5684039A (en) Chroman-2-ylmethylamino derivatives
AU722616B2 (en) 5-aminoalkoxy-1,4-dihydroquinoxaline-2,3-diones being dopamine agonists
US5081128A (en) 2,3-dihydro-1h-isoindole derivatives and their application in therapy
US5922715A (en) 5-aminoalkoxy-1, 4-dihydroquinoxaline-2, 3-diones
EP0923576B1 (fr) Derives de 4-aminoethoxy-indolone utilises en tant qu'agonistes du recepteur d2 de la dopamine
US6541502B1 (en) 2-(aminomethyl)-tetrahydro-9-oxa-1,3-diaza-cyclopenta[a]-naphthalenyl derivatives with antipsychotic activity
MXPA99007591A (en) 4-aminoethoxyindazole derivatives
US5760070A (en) 4-Aminoethoxy indolone derivatives
US6541501B2 (en) 2-(aminomethyl)-tetrahydro-9-oxa-1,3-diaza-cyclopenta[a]-naphthalenyl derivatives with antipsychotic activity
EP1073636A1 (fr) 4-amino-(ethylamino)-oxindoles utilises comme agonistes des autorecepteurs de la dopamine
US6743796B2 (en) Piperazinyl-isatins
US5972958A (en) 4-aminoalkoxy-1,3-dihydro-benzoimidazol-2-thiones
AU5915398A (en) 4-aminoalkoxy-1H-benzimidazole derivatives, their preparation and their use as dopamine autoreceptor (D2) agonists
HK1010104B (en) Chromane derivatives
MXPA99007593A (en) 5-aminoalkoxy-1,4-dihydroquinoxaline-2,3-diones being dopamine agonists

Legal Events

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

Ref document number: 131159

Country of ref document: IL

Ref document number: 98802635.X

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: 2278746

Country of ref document: CA

Ref document number: 2278746

Country of ref document: CA

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 62733/98

Country of ref document: AU

ENP Entry into the national phase

Ref document number: 1998 535841

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 337137

Country of ref document: NZ

WWE Wipo information: entry into national phase

Ref document number: 1998905000

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 1019997007413

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: PA/a/1999/007591

Country of ref document: MX

WWP Wipo information: published in national office

Ref document number: 1998905000

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: 1019997007413

Country of ref document: KR

WWW Wipo information: withdrawn in national office

Ref document number: 1998905000

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1019997007413

Country of ref document: KR