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NO20004271L - Benzylpiperazinyl and benzylpiperidinylethanone derivatives, their preparation and their use as dopamine D4 receptor antagonists - Google Patents

Benzylpiperazinyl and benzylpiperidinylethanone derivatives, their preparation and their use as dopamine D4 receptor antagonists

Info

Publication number
NO20004271L
NO20004271L NO20004271A NO20004271A NO20004271L NO 20004271 L NO20004271 L NO 20004271L NO 20004271 A NO20004271 A NO 20004271A NO 20004271 A NO20004271 A NO 20004271A NO 20004271 L NO20004271 L NO 20004271L
Authority
NO
Norway
Prior art keywords
alkyl
represents hydrogen
rog
benzylpiperidinylethanone
benzylpiperazinyl
Prior art date
Application number
NO20004271A
Other languages
Norwegian (no)
Other versions
NO20004271D0 (en
Inventor
Renata X Kover
Silva Terdjanian
Jennifer Tran
Andrew Thurkauf
Original Assignee
Neurogen 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 Neurogen Corp filed Critical Neurogen Corp
Publication of NO20004271D0 publication Critical patent/NO20004271D0/en
Publication of NO20004271L publication Critical patent/NO20004271L/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D295/00Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/14Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/145Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/15Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/18Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/30Drugs for disorders of the nervous system for treating abuse or dependence
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04Indoles; Hydrogenated indoles
    • C07D209/08Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D209/00Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/54Spiro-condensed
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D215/00Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/04Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms
    • C07D215/08Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to the ring carbon atoms with acylated ring nitrogen atom
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D265/00Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/281,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/341,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
    • C07D265/361,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D279/00Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D279/101,4-Thiazines; Hydrogenated 1,4-thiazines
    • C07D279/141,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
    • C07D279/161,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/06Heterocyclic 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 carbon chain containing only aliphatic carbon atoms

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  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Psychiatry (AREA)
  • Psychology (AREA)
  • Addiction (AREA)
  • Pain & Pain Management (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Indole Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)

Abstract

Forbindelser med formel (I) eller farmasøytisk akseptable syreaddisjonssalter derav der Y betyr oksygen eller svovel, Z betyr nitrogen eller CH, Ri, Rog Rbetyr hydrogen, halogen, hydroksy, alkoksy, alkyl, trifluormetyl eller trifluormetoksy, Rog Rbetyr hydrogen, alkyl eller danner en ring med det atom hvortil de er bundet, Rbetyr hydrogen, alkyl, alkoksy eller alkyltio, og Rbetyr hydrogen eller alkyl, eller Rog Re sammen med atomet hvortil de er bundet danner en ring, og R, R, Rg, Rio og Rn betyr hydrogen eller alkyl.Forbindelsene som beskrevet ovenfor er brukbare ved terapi og/eller prevensjon av neuropsykologiske mangler inkludert schizofreni, mani, demens, depresjon, angst, kompulsiv oppførsel, stoffmisbruk, Parkinson-lignende motormangler og mosjonsmangler relatert bruken av neuroleptiske midler.Videre beskrives mellomprodukter med formlene (VII-a) og (VII-b) der X betyr oksygen eller svovel eller CH, m er null eller et helt tall fra 1-4 og L er en avgangsgruppe.Compounds of formula (I) or pharmaceutically acceptable acid addition salts thereof wherein Y represents oxygen or sulfur, Z represents nitrogen or CH, R 1, Rog R represents hydrogen, halogen, hydroxy, alkoxy, alkyl, trifluoromethyl or trifluoromethoxy, Rog R represents hydrogen, alkyl or ring with the atom to which they are attached, R represents hydrogen, alkyl, alkoxy or alkylthio, and R represents hydrogen or alkyl, or Rog Re together with the atom to which they are attached form a ring, and R, R, Rg, Rio and R or alkyl.The compounds described above are useful in the therapy and / or prevention of neuropsychological deficits including schizophrenia, mania, dementia, depression, anxiety, compulsive behavior, substance abuse, Parkinson-like motor deficiencies and exercise deficiencies related to the use of neuroleptics. formulas (VII-a) and (VII-b) where X represents oxygen or sulfur or CH, m is zero or an integer from 1-4 and L is a leaving group.

NO20004271A 1998-02-26 2000-08-25 Benzylpiperazinyl and benzylpiperidinylethanone derivatives, their preparation and their use as dopamine D4 receptor antagonists NO20004271L (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US3098798A 1998-02-26 1998-02-26
PCT/US1999/004309 WO1999043670A1 (en) 1998-02-26 1999-02-26 Benzylpiperazinyl- and benzylpiperidinyl ethanone derivatives, their preparation and their use as dopamine d4 receptor antagonists

Publications (2)

Publication Number Publication Date
NO20004271D0 NO20004271D0 (en) 2000-08-25
NO20004271L true NO20004271L (en) 2000-10-25

Family

ID=21857045

Family Applications (1)

Application Number Title Priority Date Filing Date
NO20004271A NO20004271L (en) 1998-02-26 2000-08-25 Benzylpiperazinyl and benzylpiperidinylethanone derivatives, their preparation and their use as dopamine D4 receptor antagonists

Country Status (11)

Country Link
EP (1) EP1068193A1 (en)
JP (1) JP2002504549A (en)
KR (1) KR20010041341A (en)
CN (1) CN1293669A (en)
AU (1) AU2881499A (en)
CA (1) CA2321830A1 (en)
HU (1) HUP0100926A3 (en)
IL (1) IL137930A0 (en)
NO (1) NO20004271L (en)
PL (1) PL342597A1 (en)
WO (1) WO1999043670A1 (en)

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US6084098A (en) 1999-02-26 2000-07-04 Neurogen Corporation Benzylpiperazinyl and piperidinyl ethanone derivatives: dopamine receptor subtype specific ligands
WO2000076967A1 (en) * 1999-06-14 2000-12-21 Neurogen Corporation Benzylpiperazinyl-indolinylethanones
US6355644B1 (en) 1999-06-14 2002-03-12 Neurogen Corporation Benzylpiperazinyl-indolinylethanones
EP1177792A3 (en) 2000-07-27 2002-10-23 Pfizer Products Inc. Dopamine D4 Ligands for the treatment of novelty-seeking disorders
KR100394086B1 (en) 2000-12-04 2003-08-06 한국과학기술연구원 Novel isoxazolylalkylpiperazine derivatives having selective biological activity at dopamine D3 and D4 receptors, and preparation thereof
KR100394083B1 (en) 2000-12-04 2003-08-06 학교법인 성신학원 Novel 4,5-dihydroisoxazolylalkylpiperazine derivatives having selective biological activity at dopamine D3 and D4 receptors, and preparation thereof
CN1181065C (en) 2002-05-08 2004-12-22 上海医药工业研究院 Arylcarboxyalkylpiperazine Derivatives and Their Application as Neuroprotective Agents
DE102004027358A1 (en) * 2004-06-04 2005-12-29 Abbott Gmbh & Co. Kg Pyrimidine compounds and their use
WO2006065686A2 (en) 2004-12-13 2006-06-22 Galileo Pharmaceuticals, Inc. Spiro derivatives as lipoxygenase inhibitors
GB201106817D0 (en) 2011-04-21 2011-06-01 Astex Therapeutics Ltd New compound
DK3071203T3 (en) 2013-11-18 2021-03-15 Forma Therapeutics Inc TETRAHYDROQUINOLINE COMPOSITIONS AS BET-BROMDOMAIN INHIBITORS
RU2720237C2 (en) 2013-11-18 2020-04-28 Форма Терапеутикс, Инк. Compositions containing benzopiperazine as bromodomain bet inhibitors
LT3083616T (en) 2013-12-20 2021-09-10 Astex Therapeutics Limited BICYCLIC HETEROCYCL COMPOUNDS AND THEIR USE IN THERAPY
CN103966340B (en) * 2014-05-26 2015-09-16 宁波大学 A kind of detection kit for auxiliary diagnosis alzheimer's disease and application thereof

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Also Published As

Publication number Publication date
CN1293669A (en) 2001-05-02
KR20010041341A (en) 2001-05-15
AU2881499A (en) 1999-09-15
CA2321830A1 (en) 1999-09-02
NO20004271D0 (en) 2000-08-25
HUP0100926A2 (en) 2001-09-28
JP2002504549A (en) 2002-02-12
HUP0100926A3 (en) 2003-03-28
WO1999043670A1 (en) 1999-09-02
IL137930A0 (en) 2001-10-31
PL342597A1 (en) 2001-06-18
EP1068193A1 (en) 2001-01-17

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