JP2007513913A - 三環式インドールヒドロキシエチルアミン誘導体およびアルツハイマー病の治療におけるそれらの使用 - Google Patents
三環式インドールヒドロキシエチルアミン誘導体およびアルツハイマー病の治療におけるそれらの使用 Download PDFInfo
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- JP2007513913A JP2007513913A JP2006543488A JP2006543488A JP2007513913A JP 2007513913 A JP2007513913 A JP 2007513913A JP 2006543488 A JP2006543488 A JP 2006543488A JP 2006543488 A JP2006543488 A JP 2006543488A JP 2007513913 A JP2007513913 A JP 2007513913A
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- alkyl
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- heteroaryl
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- 208000024827 Alzheimer disease Diseases 0.000 title abstract description 11
- RUCHEPWOSATICL-UHFFFAOYSA-N 2-aminoethanol;1h-indole Chemical class NCCO.C1=CC=C2NC=CC2=C1 RUCHEPWOSATICL-UHFFFAOYSA-N 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 103
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims abstract description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 32
- 239000001257 hydrogen Substances 0.000 claims abstract description 32
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- 125000005213 alkyl heteroaryl group Chemical group 0.000 claims abstract description 22
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- 238000000034 method Methods 0.000 claims abstract description 18
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- 125000004367 cycloalkylaryl group Chemical group 0.000 claims abstract description 14
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- 125000005215 cycloalkylheteroaryl group Chemical group 0.000 claims abstract description 12
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 105
- -1 cyano, hydroxy Chemical group 0.000 claims description 80
- 239000002904 solvent Substances 0.000 claims description 35
- 150000002431 hydrogen Chemical class 0.000 claims description 24
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- 125000003545 alkoxy group Chemical group 0.000 claims description 21
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 208000037259 Amyloid Plaque Diseases 0.000 claims description 5
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- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 3
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
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- 230000002401 inhibitory effect Effects 0.000 abstract description 2
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
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- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
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- 238000010992 reflux Methods 0.000 description 11
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- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 10
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 125000005843 halogen group Chemical group 0.000 description 7
- 125000002950 monocyclic group Chemical group 0.000 description 7
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 7
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- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
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- 125000002098 pyridazinyl group Chemical group 0.000 description 1
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- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
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- 125000000168 pyrrolyl group Chemical group 0.000 description 1
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- 229960001404 quinidine Drugs 0.000 description 1
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- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
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- 239000002994 raw material Substances 0.000 description 1
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- 230000002829 reductive effect Effects 0.000 description 1
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- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 1
- 229960000311 ritonavir Drugs 0.000 description 1
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- 235000020374 simple syrup Nutrition 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
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- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229960001685 tacrine Drugs 0.000 description 1
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- HWXGLDLEGKBTEN-ZWKOTPCHSA-N tert-butyl-[(2S,3R)-3-hydroxy-4-(oxan-4-ylamino)-1-phenylbutan-2-yl]carbamic acid Chemical compound C([C@H](N(C(C)(C)C)C(O)=O)[C@H](O)CNC1CCOCC1)C1=CC=CC=C1 HWXGLDLEGKBTEN-ZWKOTPCHSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 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
- 230000000699 topical effect Effects 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- ILJSQTXMGCGYMG-UHFFFAOYSA-N triacetic acid Chemical compound CC(=O)CC(=O)CC(O)=O ILJSQTXMGCGYMG-UHFFFAOYSA-N 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 108010082372 valspodar Proteins 0.000 description 1
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- 229960001722 verapamil Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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- 235000013343 vitamin Nutrition 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/06—Peri-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
- A61P25/28—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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0328900.6A GB0328900D0 (en) | 2003-12-12 | 2003-12-12 | Novel compounds |
| PCT/EP2004/014076 WO2005058915A1 (en) | 2003-12-12 | 2004-12-09 | Tricyclic indole hydroxyethylamine derivatives and their use in the treatment of alzheimer's disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007513913A true JP2007513913A (ja) | 2007-05-31 |
| JP2007513913A5 JP2007513913A5 (https=) | 2008-01-17 |
Family
ID=30130158
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006543488A Withdrawn JP2007513913A (ja) | 2003-12-12 | 2004-12-09 | 三環式インドールヒドロキシエチルアミン誘導体およびアルツハイマー病の治療におけるそれらの使用 |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US20070073060A1 (https=) |
| EP (1) | EP1692143B1 (https=) |
| JP (1) | JP2007513913A (https=) |
| KR (1) | KR20060121164A (https=) |
| CN (1) | CN1914214A (https=) |
| AT (1) | ATE414090T1 (https=) |
| AU (1) | AU2004299231A1 (https=) |
| BR (1) | BRPI0417476A (https=) |
| CA (1) | CA2549072A1 (https=) |
| DE (1) | DE602004017777D1 (https=) |
| GB (1) | GB0328900D0 (https=) |
| IL (1) | IL175819A0 (https=) |
| IS (1) | IS8521A (https=) |
| MA (1) | MA28241A1 (https=) |
| NO (1) | NO20063137L (https=) |
| RU (1) | RU2006124863A (https=) |
| WO (1) | WO2005058915A1 (https=) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050239836A1 (en) | 2004-03-09 | 2005-10-27 | Varghese John | Substituted hydroxyethylamine aspartyl protease inhibitors |
| EP1773756A2 (en) | 2004-07-09 | 2007-04-18 | Elan Pharmaceuticals, Inc. | Oxime derivative substituted hydroxyethylamine aspartyl protease inhibitors |
| BRPI0515383A (pt) * | 2004-09-21 | 2008-07-22 | Pfizer Prod Inc | n-etil hidroxietilamina útil no tratamento de condições do snc |
| GB0422765D0 (en) * | 2004-10-13 | 2004-11-17 | Glaxo Group Ltd | Novel compounds |
| GB0422766D0 (en) * | 2004-10-13 | 2004-11-17 | Glaxo Group Ltd | Novel compounds |
| WO2007047305A1 (en) * | 2005-10-12 | 2007-04-26 | Elan Pharmaceuticals, Inc. | Methods of treating amyloidosis using cyclopropyl derivative aspartyl protease inhibitors |
| US7872009B2 (en) | 2005-11-21 | 2011-01-18 | Amgen Inc. | Beta-Secretase modulators and methods of use |
| US7838676B2 (en) * | 2005-11-21 | 2010-11-23 | Amgen Inc. | Beta-secretase modulators and methods of use |
| PT2185561E (pt) * | 2007-07-27 | 2011-09-07 | Sanofi Aventis | Derivados de 1,2,3,4-tetra-hidropirrolo(1,2-a)pirazina-6- carboxamidas e de 2,3,4,5-tetra-hidropirrolo(1,2-a)-diazepina-7- carboxamidas, sua preparação e sua aplicação em terapia |
| FR2919289B1 (fr) * | 2007-07-27 | 2009-09-04 | Sanofi Aventis Sa | Derives de 2,3,4,5-tetrahydropyrrolo[1,2-a][1,4]- diazepine-7-carboxamides, leur preparation et leur application en therapeutique. |
| FR2919288B1 (fr) * | 2007-07-27 | 2009-09-04 | Sanofi Aventis Sa | Derives de 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-6- carboxamides, leur preparation et leur application en therapeutique. |
| FR2919286A1 (fr) | 2007-07-27 | 2009-01-30 | Sanofi Aventis Sa | Derives de derives de 1-oxo-1,2-dihydroisoquinoleine-5- carboxamides et de 4-oxo-3,4-dihydroquinazoline-8- carboxamides,leur preparation et leur application en therapeutique. |
| FR2919285B1 (fr) | 2007-07-27 | 2012-08-31 | Sanofi Aventis | Derives de 1-oxo-isoindoline-4-carboxamides et de 1-oxo- 1,2,3,4-tetrahydroisoquinoleine-5-carboxamides, leur preparation et leur application en therapeutique. |
| EP2310019A4 (en) * | 2008-05-29 | 2011-06-01 | Albany Molecular Res Inc | 5-HT3 RECEPTOR MODULATORS, MANUFACTURING METHOD AND ITS USE |
| FR2960876B1 (fr) | 2010-06-03 | 2012-07-27 | Sanofi Aventis | Derives de 3,4-dihydropyrrolo[1,2-a]pyrazine-2,8(1h)-dicarboxamide leur preparation et leur application en therapeutique. |
| AU2011261375B2 (en) | 2010-06-04 | 2016-09-22 | Albany Molecular Research, Inc. | Glycine transporter-1 inhibitors, methods of making them, and uses thereof |
| CN104768949A (zh) * | 2012-08-24 | 2015-07-08 | 特温蒂斯公司 | 苯并呋咱抗淀粉样蛋白化合物和方法 |
| US12043631B2 (en) | 2017-10-13 | 2024-07-23 | Purdue Research Foundation | BACE1 inhibitors for the treatment of Alzheimer's disease |
| WO2019075358A1 (en) * | 2017-10-13 | 2019-04-18 | Ghosh Arun K | BACE1 INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2280096A1 (en) * | 1997-02-04 | 1998-08-06 | The Regents Of The University Of California | Nanomolar, non-peptide inhibitors of cathepsin d |
| US6207664B1 (en) * | 1998-11-25 | 2001-03-27 | Pfizer Inc. | Squalene synthetase inhibitor agents |
| DE60124080T2 (de) * | 2000-03-23 | 2007-03-01 | Elan Pharmaceuticals, Inc., San Francisco | Verbindungen und verfahren zur behandlung der alzheimerschen krankheit |
| EP1299352B1 (en) * | 2000-06-30 | 2005-12-28 | Elan Pharmaceuticals, Inc. | Compounds to treat alzheimer's disease |
| NZ533107A (en) * | 2001-11-08 | 2007-04-27 | Upjohn Co | N, N'-substituted-1,3-diamino-2-hydroxypropane derivatives |
| GB0228410D0 (en) * | 2002-12-05 | 2003-01-08 | Glaxo Group Ltd | Novel Compounds |
| GB0309221D0 (en) * | 2003-04-23 | 2003-06-04 | Glaxo Group Ltd | Novel compounds |
-
2003
- 2003-12-12 GB GBGB0328900.6A patent/GB0328900D0/en not_active Ceased
-
2004
- 2004-12-09 DE DE602004017777T patent/DE602004017777D1/de not_active Expired - Fee Related
- 2004-12-09 EP EP04803724A patent/EP1692143B1/en not_active Expired - Lifetime
- 2004-12-09 AT AT04803724T patent/ATE414090T1/de not_active IP Right Cessation
- 2004-12-09 JP JP2006543488A patent/JP2007513913A/ja not_active Withdrawn
- 2004-12-09 US US10/596,296 patent/US20070073060A1/en not_active Abandoned
- 2004-12-09 CA CA002549072A patent/CA2549072A1/en not_active Abandoned
- 2004-12-09 AU AU2004299231A patent/AU2004299231A1/en not_active Abandoned
- 2004-12-09 RU RU2006124863/04A patent/RU2006124863A/ru not_active Application Discontinuation
- 2004-12-09 BR BRPI0417476-3A patent/BRPI0417476A/pt not_active IP Right Cessation
- 2004-12-09 WO PCT/EP2004/014076 patent/WO2005058915A1/en not_active Ceased
- 2004-12-09 CN CNA2004800416435A patent/CN1914214A/zh active Pending
- 2004-12-09 KR KR1020067011376A patent/KR20060121164A/ko not_active Withdrawn
-
2006
- 2006-05-22 IL IL175819A patent/IL175819A0/en unknown
- 2006-06-26 MA MA29143A patent/MA28241A1/fr unknown
- 2006-06-26 IS IS8521A patent/IS8521A/xx unknown
- 2006-07-06 NO NO20063137A patent/NO20063137L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| IL175819A0 (en) | 2006-10-05 |
| KR20060121164A (ko) | 2006-11-28 |
| BRPI0417476A (pt) | 2007-05-08 |
| AU2004299231A1 (en) | 2005-06-30 |
| EP1692143A1 (en) | 2006-08-23 |
| IS8521A (is) | 2006-06-26 |
| DE602004017777D1 (de) | 2008-12-24 |
| CA2549072A1 (en) | 2005-06-30 |
| EP1692143B1 (en) | 2008-11-12 |
| NO20063137L (no) | 2006-08-31 |
| RU2006124863A (ru) | 2008-01-20 |
| WO2005058915A1 (en) | 2005-06-30 |
| ATE414090T1 (de) | 2008-11-15 |
| US20070073060A1 (en) | 2007-03-29 |
| CN1914214A (zh) | 2007-02-14 |
| GB0328900D0 (en) | 2004-01-14 |
| MA28241A1 (fr) | 2006-10-02 |
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