WO2008154442A1 - Therapeutic pyrazoloquinoline urea derivatives - Google Patents

Therapeutic pyrazoloquinoline urea derivatives Download PDF

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Publication number
WO2008154442A1
WO2008154442A1 PCT/US2008/066205 US2008066205W WO2008154442A1 WO 2008154442 A1 WO2008154442 A1 WO 2008154442A1 US 2008066205 W US2008066205 W US 2008066205W WO 2008154442 A1 WO2008154442 A1 WO 2008154442A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
alkyl
fluoro
optionally substituted
animal
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/US2008/066205
Other languages
English (en)
French (fr)
Inventor
Alan P. Kaplan
Varsha Gupta
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.)
Helicon Therapeutics Inc
Original Assignee
Helicon Therapeutics Inc
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 to HK10109113.1A priority Critical patent/HK1142496B/en
Priority to ES08770406T priority patent/ES2433566T3/es
Priority to JP2010511389A priority patent/JP2010529144A/ja
Priority to CN200880023876A priority patent/CN101686682A/zh
Priority to EP08770406.0A priority patent/EP2164328B8/en
Priority to CA002688405A priority patent/CA2688405A1/en
Priority to MX2009013205A priority patent/MX2009013205A/es
Priority to AU2008261888A priority patent/AU2008261888A1/en
Priority to BRPI0812347A priority patent/BRPI0812347A2/pt
Application filed by Helicon Therapeutics Inc filed Critical Helicon Therapeutics Inc
Publication of WO2008154442A1 publication Critical patent/WO2008154442A1/en
Priority to IL202286A priority patent/IL202286A0/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • 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
    • A61P25/20—Hypnotics; Sedatives
    • 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
    • A61P25/22—Anxiolytics
    • 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
    • A61P25/28—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
    • 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

Definitions

  • Ri can be hydrogen
  • R 2 can be hydrogen, fluoro, methyl, morpholinyl, or methoxy.
  • the chloro-quinoline of formula 3 can be reacted with aryl or heteroaryl hydrazine to form the tricyclic oxo-pyrazole of formula 4.
  • Organic bases that can be used in step (d) include but are not limited to triethyl amine (TEA), diisopropylethyl amine (DIEA), 1,8- Diazabicyclo[5.4.0]undec-7-ene (DBU), l,5-Diazabicyclo[4.3.0]non-5-ene (DBN), N- methylpiperidine, and the like.
  • the chloro-methylquinoline of formula 3g can be reacted with arylhydrazine or heteroarylhydrazine to form the tricyclic oxo-pyrazole of formula 4i.
  • Organic bases that can be used in step (c) include but are not limited to triethyl amine (TEA), diisopropylethyl amine (DIEA), l,8-Diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5- Diazabicyclo[4.3.0]non-5-ene (DBN), N-methylpiperidine, and the like.
  • the compounds of formula (I) can be formulated as pharmaceutical compositions and administered to a mammalian host, such as a human patient in a variety of forms adapted to the chosen route of administration, i.e., orally or parenterally, by intravenous, intramuscular, topical or subcutaneous routes.
  • I is the control response at the GABA EC 20 and F the response in the presence of modulator (Lippa A, et al. (2005) Proc. Natl. Acad. ScI USA 102(20): 7380-7385 incorporated herein in its entirety).

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Anesthesiology (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
PCT/US2008/066205 2007-06-08 2008-06-06 Therapeutic pyrazoloquinoline urea derivatives Ceased WO2008154442A1 (en)

Priority Applications (10)

Application Number Priority Date Filing Date Title
AU2008261888A AU2008261888A1 (en) 2007-06-08 2008-06-06 Therapeutic pyrazoloquinoline urea derivatives
ES08770406T ES2433566T3 (es) 2007-06-08 2008-06-06 Derivados terapéuticos de pirazoloquinolinurea
JP2010511389A JP2010529144A (ja) 2007-06-08 2008-06-06 治療用ピラゾロキノリン尿素誘導体
CN200880023876A CN101686682A (zh) 2007-06-08 2008-06-06 治疗用吡唑并喹啉脲衍生物
EP08770406.0A EP2164328B8 (en) 2007-06-08 2008-06-06 Therapeutic pyrazoloquinoline urea derivatives
HK10109113.1A HK1142496B (en) 2007-06-08 2008-06-06 Therapeutic pyrazoloquinoline urea derivatives
MX2009013205A MX2009013205A (es) 2007-06-08 2008-06-06 Derivados de pirazoloquinolina urea terapeuticos.
CA002688405A CA2688405A1 (en) 2007-06-08 2008-06-06 Therapeutic pyrazoloquinoline urea derivatives
BRPI0812347A BRPI0812347A2 (pt) 2007-06-08 2008-06-06 composto, composição farmacêutica e métodos de modulação de um ou mais subtipos de gabaa, de aumento da função cognitiva e de tratamento de deficiência orgânica cognitiva em animal e usos do composto
IL202286A IL202286A0 (en) 2007-06-08 2009-11-23 Therapeutic pyrazoloquinoline urea derivatives

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US94299207P 2007-06-08 2007-06-08
US60/942,992 2007-06-08

Publications (1)

Publication Number Publication Date
WO2008154442A1 true WO2008154442A1 (en) 2008-12-18

Family

ID=40096439

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/066205 Ceased WO2008154442A1 (en) 2007-06-08 2008-06-06 Therapeutic pyrazoloquinoline urea derivatives

Country Status (12)

Country Link
US (2) US7863266B2 (enExample)
EP (1) EP2164328B8 (enExample)
JP (1) JP2010529144A (enExample)
KR (1) KR20100038189A (enExample)
CN (1) CN101686682A (enExample)
AU (1) AU2008261888A1 (enExample)
BR (1) BRPI0812347A2 (enExample)
CA (1) CA2688405A1 (enExample)
ES (1) ES2433566T3 (enExample)
IL (1) IL202286A0 (enExample)
MX (1) MX2009013205A (enExample)
WO (1) WO2008154442A1 (enExample)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2490692A4 (en) * 2009-10-21 2013-03-13 Merck Sharp & Dohme CHINOLINONE PYRAZOLON M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
WO2013120438A1 (zh) 2012-02-14 2013-08-22 中国科学院上海生命科学研究院 治疗或缓解疼痛的物质
EP2643000A4 (en) * 2010-09-22 2014-05-21 Dart Neuroscience Cayman Ltd THERAPEUTIC PIPERAZINES

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008154442A1 (en) * 2007-06-08 2008-12-18 Helicon Therapeutics, Inc. Therapeutic pyrazoloquinoline urea derivatives
FR2962335B1 (fr) * 2010-07-12 2013-01-18 Cll Pharma Utilisation du nonapeptide pat dans le traitement et la prevention des maladies neurodegeneratives
US9468662B2 (en) 2010-07-12 2016-10-18 Orphit Use of the PAT nonapeptide in the treatment and prevention of neurodegenerative diseases
CN106187887B (zh) * 2016-07-01 2018-08-14 上海工程技术大学 4-羟基喹啉-3-甲酸的制备方法
DK3538512T3 (da) 2016-11-11 2021-07-05 Bayer Animal Health Gmbh Nye anthelmintiske quinolin-3-carboxamid-derivater

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4814450A (en) * 1984-07-09 1989-03-21 Ciba-Geigy Corporation Certain ring-fused pyrazolo[3,4-d]-pyridin-3-one derivatives
US20050245563A1 (en) * 2003-05-29 2005-11-03 Millennium Pharmaceuticals, Inc. Chk-1 inhibitors
US20060035919A1 (en) * 2002-12-16 2006-02-16 Matthews Lan R Tetracylic immunomodulatory compounds

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ATE8629T1 (de) * 1979-06-21 1984-08-15 Ciba-Geigy Ag Pyrazolochinoline, verfahren zu ihrer herstellung, und pharmazeutische praeparate enthaltend diese verbindungen.
DE3204126A1 (de) 1982-02-06 1983-08-11 Bayer Ag, 5090 Leverkusen Pyrazoloxazine, -thiazine, -chinoline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel
US4524146A (en) * 1982-12-08 1985-06-18 Ciba-Geigy Corporation Certain -2-heterocycle substituted pyrazoloquinolines
JPS61112075A (ja) * 1984-11-05 1986-05-30 Shionogi & Co Ltd チエニルピラゾロキノリン誘導体
EP0214092A1 (en) 1985-08-08 1987-03-11 Ciba-Geigy Ag Enhanced absorption of psychoactive 2-aryl-pyrazolo quinolines as a solid molecular dispersion in polyvinylpyrrolidone
WO1992022552A1 (en) * 1991-06-14 1992-12-23 The Upjohn Company IMIDAZO[1,5-a]QUINOXALINES
US5334595A (en) 1992-10-23 1994-08-02 Sterling Winthrop Inc. Pyrazoloquinolones as anticancer agents
US5792766A (en) * 1996-03-13 1998-08-11 Neurogen Corporation Imidazo 1,5-c! quinazolines; a new class of GABA brain receptor ligands
GB9716344D0 (en) * 1997-08-01 1997-10-08 Merck Sharp & Dohme Therapeutic compounds
GB9716345D0 (en) * 1997-08-01 1997-10-08 Merck Sharp & Dohme Therapeutic compounds
GB9716347D0 (en) * 1997-08-01 1997-10-08 Merck Sharp & Dohme Therapeutic compounds
TWI271406B (en) 1999-12-13 2007-01-21 Eisai Co Ltd Tricyclic condensed heterocyclic compounds, preparation method of the same and pharmaceuticals comprising the same
DE60214138T2 (de) * 2001-02-21 2007-03-29 Janssen Pharmaceutica N.V. Isoxazolin-derivate als antidepressiva
JP3896309B2 (ja) 2001-07-09 2007-03-22 ファイザー株式会社 プロテインキナーゼｃ阻害物質としてのピラゾロキノリノン誘導体
US7544697B2 (en) 2003-10-03 2009-06-09 Coley Pharmaceutical Group, Inc. Pyrazolopyridines and analogs thereof
CA2621560A1 (en) 2005-09-07 2007-03-15 Braincells, Inc. Modulation of neurogenesis by hdac inhibition
KR101052122B1 (ko) * 2005-10-25 2011-07-26 시오노기세야쿠 가부시키가이샤 아미노디히드로티아진 유도체
JP2010529143A (ja) * 2007-06-08 2010-08-26 ヘリコン・セラピューティクス・インコーポレーテッド 治療用ピラゾロキノリン誘導体
WO2008154442A1 (en) * 2007-06-08 2008-12-18 Helicon Therapeutics, Inc. Therapeutic pyrazoloquinoline urea derivatives
JP2010529145A (ja) * 2007-06-08 2010-08-26 ヘリコン・セラピューティクス・インコーポレーテッド 治療用ピラゾロナフチリジン誘導体

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4814450A (en) * 1984-07-09 1989-03-21 Ciba-Geigy Corporation Certain ring-fused pyrazolo[3,4-d]-pyridin-3-one derivatives
US20060035919A1 (en) * 2002-12-16 2006-02-16 Matthews Lan R Tetracylic immunomodulatory compounds
US20050245563A1 (en) * 2003-05-29 2005-11-03 Millennium Pharmaceuticals, Inc. Chk-1 inhibitors

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP2164328A4 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2490692A4 (en) * 2009-10-21 2013-03-13 Merck Sharp & Dohme CHINOLINONE PYRAZOLON M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
US8895580B2 (en) 2009-10-21 2014-11-25 Merck Sharp & Dohme Corp. Quinolinone-pyrazolone M1 receptor positive allosteric modulators
EP2643000A4 (en) * 2010-09-22 2014-05-21 Dart Neuroscience Cayman Ltd THERAPEUTIC PIPERAZINES
WO2013120438A1 (zh) 2012-02-14 2013-08-22 中国科学院上海生命科学研究院 治疗或缓解疼痛的物质

Also Published As

Publication number Publication date
MX2009013205A (es) 2010-04-09
AU2008261888A1 (en) 2008-12-18
BRPI0812347A2 (pt) 2016-08-02
JP2010529144A (ja) 2010-08-26
EP2164328A1 (en) 2010-03-24
HK1142496A1 (en) 2010-12-10
IL202286A0 (en) 2010-06-16
ES2433566T3 (es) 2013-12-11
US7863266B2 (en) 2011-01-04
EP2164328B1 (en) 2013-08-07
CN101686682A (zh) 2010-03-31
EP2164328B8 (en) 2013-09-11
CA2688405A1 (en) 2008-12-18
EP2164328A4 (en) 2010-06-23
KR20100038189A (ko) 2010-04-13
US8343957B2 (en) 2013-01-01
US20080306048A1 (en) 2008-12-11
US20110071140A1 (en) 2011-03-24

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