JP2010529143A - 治療用ピラゾロキノリン誘導体 - Google Patents
治療用ピラゾロキノリン誘導体 Download PDFInfo
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- JP2010529143A JP2010529143A JP2010511387A JP2010511387A JP2010529143A JP 2010529143 A JP2010529143 A JP 2010529143A JP 2010511387 A JP2010511387 A JP 2010511387A JP 2010511387 A JP2010511387 A JP 2010511387A JP 2010529143 A JP2010529143 A JP 2010529143A
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- JP
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- Prior art keywords
- formula
- alkyl
- pharmaceutically acceptable
- tautomer
- acceptable salt
- 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.)
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- UXYHZIYEDDINQH-UHFFFAOYSA-N C1=CNC2=C3C=NN=C3C=CC2=C1 Chemical class C1=CNC2=C3C=NN=C3C=CC2=C1 UXYHZIYEDDINQH-UHFFFAOYSA-N 0.000 title description 6
- 230000001225 therapeutic effect Effects 0.000 title description 3
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- 238000000034 method Methods 0.000 claims abstract description 150
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- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims abstract description 54
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims abstract description 52
- 239000003814 drug Substances 0.000 claims abstract description 19
- 238000004519 manufacturing process Methods 0.000 claims abstract description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 5
- 150000003839 salts Chemical class 0.000 claims description 100
- 125000003118 aryl group Chemical group 0.000 claims description 95
- 229910052757 nitrogen Inorganic materials 0.000 claims description 80
- 125000000217 alkyl group Chemical group 0.000 claims description 67
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 56
- -1 -NR a R b Chemical group 0.000 claims description 48
- 125000001153 fluoro group Chemical group F* 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 39
- 239000001257 hydrogen Substances 0.000 claims description 38
- 239000000203 mixture Substances 0.000 claims description 36
- 125000000623 heterocyclic group Chemical group 0.000 claims description 32
- 125000001072 heteroaryl group Chemical group 0.000 claims description 29
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 28
- 230000015654 memory Effects 0.000 claims description 25
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
- 125000005843 halogen group Chemical group 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
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- 125000004193 piperazinyl group Chemical group 0.000 description 1
- LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 description 1
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
- BRRMEKWBTRNYBF-UHFFFAOYSA-N piperidine;1h-quinolin-2-one Chemical compound C1CCNCC1.C1=CC=CC2=NC(O)=CC=C21 BRRMEKWBTRNYBF-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000651 prodrug Chemical class 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- HREHOXSRYOZKNT-UHFFFAOYSA-N quinolin-2-ylmethanol Chemical compound C1=CC=CC2=NC(CO)=CC=C21 HREHOXSRYOZKNT-UHFFFAOYSA-N 0.000 description 1
- PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
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- 125000006413 ring segment Chemical group 0.000 description 1
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- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
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- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- FNXKBSAUKFCXIK-UHFFFAOYSA-M sodium;hydrogen carbonate;8-hydroxy-7-iodoquinoline-5-sulfonic acid Chemical class [Na+].OC([O-])=O.C1=CN=C2C(O)=C(I)C=C(S(O)(=O)=O)C2=C1 FNXKBSAUKFCXIK-UHFFFAOYSA-M 0.000 description 1
- 239000007892 solid unit dosage form Substances 0.000 description 1
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- 235000010199 sorbic acid Nutrition 0.000 description 1
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- 229940075582 sorbic acid Drugs 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 229940072040 tricaine Drugs 0.000 description 1
- FQZJYWMRQDKBQN-UHFFFAOYSA-N tricaine methanesulfonate Chemical compound CS([O-])(=O)=O.CCOC(=O)C1=CC=CC([NH3+])=C1 FQZJYWMRQDKBQN-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
- 229960001475 zolpidem Drugs 0.000 description 1
- ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 description 1
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
-
- 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
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)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US94300507P | 2007-06-08 | 2007-06-08 | |
| PCT/US2008/066201 WO2008154438A1 (en) | 2007-06-08 | 2008-06-06 | Therapeutic pyrazoloquinoline derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010529143A true JP2010529143A (ja) | 2010-08-26 |
| JP2010529143A5 JP2010529143A5 (enExample) | 2011-07-14 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010511387A Pending JP2010529143A (ja) | 2007-06-08 | 2008-06-06 | 治療用ピラゾロキノリン誘導体 |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US7872002B2 (enExample) |
| EP (1) | EP2166852B1 (enExample) |
| JP (1) | JP2010529143A (enExample) |
| KR (1) | KR20100039331A (enExample) |
| CN (1) | CN101742908A (enExample) |
| AT (1) | ATE544344T1 (enExample) |
| AU (1) | AU2008261884A1 (enExample) |
| BR (1) | BRPI0812366A2 (enExample) |
| CA (1) | CA2688395A1 (enExample) |
| ES (1) | ES2386168T3 (enExample) |
| IL (1) | IL202270A0 (enExample) |
| MX (1) | MX2009013202A (enExample) |
| WO (1) | WO2008154438A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010529144A (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尿素誘導体 |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2483728T3 (es) * | 2007-06-08 | 2014-08-07 | Dart Neuroscience (Cayman) Ltd | Derivados terapéuticos de pirazolonafatiridina |
| ES2386168T3 (es) * | 2007-06-08 | 2012-08-10 | Helicon Therapeutics, Inc. | Derivados de pirazoloquinolina terapéuticos |
| US20150374705A1 (en) | 2012-02-14 | 2015-12-31 | Shanghai Institues for Biological Sciences | Substances for treatment or relief of pain |
| WO2017085053A1 (en) | 2015-11-16 | 2017-05-26 | Fundación Para La Investigación Médica Aplicada | Novel compounds as inhibitors of dna methyltransferases |
| CN105294648B (zh) * | 2015-11-30 | 2017-11-28 | 山东罗欣药业集团股份有限公司 | 一种西他沙星的制备方法 |
| CN116390923B (zh) * | 2020-08-21 | 2025-08-29 | 浙江海正药业股份有限公司 | 杂环类衍生物及其制备方法和用途 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| WO1999006401A1 (en) * | 1997-08-01 | 1999-02-11 | Merck Sharp & Dohme Limited | 2-ARYL-2,5-DIHYDRO-PYRAZOLO[4,3-c]QUINOLIN-3-ONES AS GABA ALPHA 5 RECEPTOR INVERSE AGONISTS |
| WO2002081474A1 (en) * | 2001-04-04 | 2002-10-17 | Merck Sharp & Dohme Limited | Triazolophthalazine / quinoline / isoquinoline derivatives which are ligands for gaba-a receptors containing the alpha 5 subtype |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3204126A1 (de) * | 1982-02-06 | 1983-08-11 | Bayer Ag, 5090 Leverkusen | Pyrazoloxazine, -thiazine, -chinoline, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| US4814450A (en) | 1984-07-09 | 1989-03-21 | Ciba-Geigy Corporation | Certain ring-fused pyrazolo[3,4-d]-pyridin-3-one derivatives |
| 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 |
| US5334595A (en) * | 1992-10-23 | 1994-08-02 | Sterling Winthrop Inc. | Pyrazoloquinolones as anticancer agents |
| 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 |
| 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 |
| ATE425164T1 (de) | 2002-12-16 | 2009-03-15 | Active Biotech Ab | Tetrazyklische immunmodulierende verbindungen |
| AR045689A1 (es) | 2003-05-29 | 2005-11-09 | Millennium Pharm Inc | Compuestos derivados de 2,5-dihidro-pirazolo[4,3-c]quinolin-4-ona como inhibidores de chk-1 y composiciones farmaceuticas que los contienen |
| US7544697B2 (en) | 2003-10-03 | 2009-06-09 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridines and analogs thereof |
| AU2006287378A1 (en) | 2005-09-07 | 2007-03-15 | Braincells, Inc. | Modulation of neurogenesis by HDac inhibition |
| JP2008047893A (ja) * | 2006-08-11 | 2008-02-28 | Samsung Electronics Co Ltd | 薄膜トランジスタ表示板及びその製造方法 |
| ES2386168T3 (es) * | 2007-06-08 | 2012-08-10 | Helicon Therapeutics, Inc. | Derivados de pirazoloquinolina terapéuticos |
-
2008
- 2008-06-06 ES ES08770402T patent/ES2386168T3/es active Active
- 2008-06-06 KR KR1020107000330A patent/KR20100039331A/ko not_active Withdrawn
- 2008-06-06 CN CN200880024823A patent/CN101742908A/zh active Pending
- 2008-06-06 US US12/135,036 patent/US7872002B2/en not_active Expired - Fee Related
- 2008-06-06 EP EP08770402A patent/EP2166852B1/en not_active Not-in-force
- 2008-06-06 MX MX2009013202A patent/MX2009013202A/es active IP Right Grant
- 2008-06-06 AT AT08770402T patent/ATE544344T1/de active
- 2008-06-06 CA CA002688395A patent/CA2688395A1/en not_active Abandoned
- 2008-06-06 AU AU2008261884A patent/AU2008261884A1/en not_active Abandoned
- 2008-06-06 BR BRPI0812366A patent/BRPI0812366A2/pt not_active IP Right Cessation
- 2008-06-06 WO PCT/US2008/066201 patent/WO2008154438A1/en not_active Ceased
- 2008-06-06 JP JP2010511387A patent/JP2010529143A/ja active Pending
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2009
- 2009-11-22 IL IL202270A patent/IL202270A0/en unknown
-
2010
- 2010-11-18 US US12/949,655 patent/US8598159B2/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| WO1999006401A1 (en) * | 1997-08-01 | 1999-02-11 | Merck Sharp & Dohme Limited | 2-ARYL-2,5-DIHYDRO-PYRAZOLO[4,3-c]QUINOLIN-3-ONES AS GABA ALPHA 5 RECEPTOR INVERSE AGONISTS |
| WO2002081474A1 (en) * | 2001-04-04 | 2002-10-17 | Merck Sharp & Dohme Limited | Triazolophthalazine / quinoline / isoquinoline derivatives which are ligands for gaba-a receptors containing the alpha 5 subtype |
Non-Patent Citations (1)
| Title |
|---|
| JPN6013028844; Ｃａｒｏｔｔｉ Ａ． ｅｔ ａｌ: Ｂｉｏｏｒｇａｎｉｃ ＆ Ｍｅｄｉｃｉｎａｌ Ｃｈｅｍｉｓｔｒｙ ｖｏｌ．１１, 2003, ｐｐ．５２５９-５２７２ * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2010529144A (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尿素誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101742908A (zh) | 2010-06-16 |
| ATE544344T1 (de) | 2012-02-15 |
| AU2008261884A1 (en) | 2008-12-18 |
| EP2166852A1 (en) | 2010-03-31 |
| ES2386168T3 (es) | 2012-08-10 |
| IL202270A0 (en) | 2010-06-16 |
| BRPI0812366A2 (pt) | 2016-08-02 |
| EP2166852B1 (en) | 2012-02-08 |
| US20110065693A1 (en) | 2011-03-17 |
| HK1142775A1 (en) | 2010-12-17 |
| US8598159B2 (en) | 2013-12-03 |
| US7872002B2 (en) | 2011-01-18 |
| MX2009013202A (es) | 2010-04-09 |
| US20080306049A1 (en) | 2008-12-11 |
| EP2166852A4 (en) | 2010-07-07 |
| WO2008154438A1 (en) | 2008-12-18 |
| CA2688395A1 (en) | 2008-12-18 |
| KR20100039331A (ko) | 2010-04-15 |
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