JP2010500999A - ベータ−セクレターゼの阻害剤としてのイミダゾールアミン - Google Patents
ベータ−セクレターゼの阻害剤としてのイミダゾールアミン Download PDFInfo
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- JP2010500999A JP2010500999A JP2009524746A JP2009524746A JP2010500999A JP 2010500999 A JP2010500999 A JP 2010500999A JP 2009524746 A JP2009524746 A JP 2009524746A JP 2009524746 A JP2009524746 A JP 2009524746A JP 2010500999 A JP2010500999 A JP 2010500999A
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- compound
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- phenyl
- alkyl
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- 108010043324 Amyloid Precursor Protein Secretases Proteins 0.000 title description 12
- 102000002659 Amyloid Precursor Protein Secretases Human genes 0.000 title description 12
- 239000003112 inhibitor Substances 0.000 title description 12
- DEPDDPLQZYCHOH-UHFFFAOYSA-N 1h-imidazol-2-amine Chemical compound NC1=NC=CN1 DEPDDPLQZYCHOH-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 100
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 30
- 102000013455 Amyloid beta-Peptides Human genes 0.000 claims abstract description 19
- 108010090849 Amyloid beta-Peptides Proteins 0.000 claims abstract description 19
- 208000035475 disorder Diseases 0.000 claims abstract description 16
- 201000010099 disease Diseases 0.000 claims abstract description 14
- 230000002265 prevention Effects 0.000 claims abstract description 9
- 230000006933 amyloid-beta aggregation Effects 0.000 claims abstract description 7
- -1 cycloheteroalkyl Chemical group 0.000 claims description 45
- 229910052760 oxygen Inorganic materials 0.000 claims description 28
- 238000002360 preparation method Methods 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000001072 heteroaryl group Chemical group 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 22
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 16
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- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 13
- 101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 claims description 13
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 12
- 102100021257 Beta-secretase 1 Human genes 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
- MWIWQVPHIMOAEB-UHFFFAOYSA-N 2h-oxadiazin-6-amine Chemical compound NC1=CC=NNO1 MWIWQVPHIMOAEB-UHFFFAOYSA-N 0.000 claims description 7
- 208000037259 Amyloid Plaque Diseases 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 5
- SIFXKACBEOUPOD-UHFFFAOYSA-N 8-[3-(2-fluoropyridin-3-yl)phenyl]-8-pyridin-4-yl-3,4-dihydro-2h-imidazo[1,5-a]pyrimidin-6-amine Chemical compound C12=NCCCN2C(N)=NC1(C=1C=C(C=CC=1)C=1C(=NC=CC=1)F)C1=CC=NC=C1 SIFXKACBEOUPOD-UHFFFAOYSA-N 0.000 claims description 4
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000003107 substituted aryl group Chemical group 0.000 claims description 4
- BTKIVAGPTLXEER-UHFFFAOYSA-N 8-[3-(2-fluoropyridin-3-yl)phenyl]-8-[1-(2,2,2-trifluoroethyl)pyrazol-4-yl]-3,4-dihydro-2h-imidazo[1,5-a]pyrimidin-6-amine Chemical compound C12=NCCCN2C(N)=NC1(C=1C=C(C=CC=1)C=1C(=NC=CC=1)F)C=1C=NN(CC(F)(F)F)C=1 BTKIVAGPTLXEER-UHFFFAOYSA-N 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 229910052763 palladium Inorganic materials 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- ARUUYPWKFNUVFQ-UHFFFAOYSA-N 8-(1-ethylpyrazol-4-yl)-8-[3-(2-fluoropyridin-3-yl)phenyl]-3,4-dihydro-2h-imidazo[1,5-a]pyrimidin-6-amine Chemical compound C1=NN(CC)C=C1C1(C=2C=C(C=CC=2)C=2C(=NC=CC=2)F)C2=NCCCN2C(N)=N1 ARUUYPWKFNUVFQ-UHFFFAOYSA-N 0.000 claims description 2
- RRDVLXWUXDSNDZ-UHFFFAOYSA-N 8-(2,6-diethylpyridin-4-yl)-8-[3-(2-fluoropyridin-3-yl)phenyl]-3,4-dihydro-2h-imidazo[1,5-a]pyrimidin-6-amine Chemical compound CCC1=NC(CC)=CC(C2(C3=NCCCN3C(N)=N2)C=2C=C(C=CC=2)C=2C(=NC=CC=2)F)=C1 RRDVLXWUXDSNDZ-UHFFFAOYSA-N 0.000 claims description 2
- 206010044688 Trisomy 21 Diseases 0.000 claims description 2
- 230000006999 cognitive decline Effects 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 208000024667 ABeta amyloidosis, Dutch type Diseases 0.000 claims 1
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims 1
- 208000028698 Cognitive impairment Diseases 0.000 claims 1
- 206010039966 Senile dementia Diseases 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 208000036536 dutch type ABeta amyloidosis Diseases 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 32
- 239000000203 mixture Substances 0.000 description 32
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
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- 238000005481 NMR spectroscopy Methods 0.000 description 23
- 239000000758 substrate Substances 0.000 description 23
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 18
- 239000000908 ammonium hydroxide Substances 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 238000003818 flash chromatography Methods 0.000 description 16
- 239000000377 silicon dioxide Substances 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 239000012267 brine Substances 0.000 description 12
- 238000010586 diagram Methods 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 12
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
- 102000004190 Enzymes Human genes 0.000 description 11
- 108090000790 Enzymes Proteins 0.000 description 11
- 101800001718 Amyloid-beta protein Proteins 0.000 description 10
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 229940125904 compound 1 Drugs 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
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- 229940125782 compound 2 Drugs 0.000 description 9
- 230000007017 scission Effects 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 8
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 8
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 8
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 8
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 8
- 210000004556 brain Anatomy 0.000 description 8
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- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- 239000000872 buffer Substances 0.000 description 7
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 7
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- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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- 125000004438 haloalkoxy group Chemical group 0.000 description 3
- 125000001188 haloalkyl group Chemical group 0.000 description 3
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 3
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—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
- A61P25/28—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
-
- 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
- C07D471/12—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 three hetero rings
- C07D471/20—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/20—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical 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)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US83835706P | 2006-08-17 | 2006-08-17 | |
| PCT/US2007/075690 WO2008022024A2 (en) | 2006-08-17 | 2007-08-10 | Imidazole amines as inhibitors of beta-secretase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2010500999A true JP2010500999A (ja) | 2010-01-14 |
Family
ID=38988046
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009524746A Withdrawn JP2010500999A (ja) | 2006-08-17 | 2007-08-10 | ベータ−セクレターゼの阻害剤としてのイミダゾールアミン |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP2054414A2 (es) |
| JP (1) | JP2010500999A (es) |
| AR (1) | AR062409A1 (es) |
| CA (1) | CA2660441A1 (es) |
| CL (1) | CL2007002288A1 (es) |
| MX (1) | MX2009001699A (es) |
| PE (1) | PE20080744A1 (es) |
| TW (1) | TW200817406A (es) |
| WO (1) | WO2008022024A2 (es) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7763609B2 (en) | 2003-12-15 | 2010-07-27 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| US7592348B2 (en) | 2003-12-15 | 2009-09-22 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| US7700603B2 (en) | 2003-12-15 | 2010-04-20 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| KR20080029965A (ko) | 2005-06-14 | 2008-04-03 | 쉐링 코포레이션 | 아스파르틸 프로테아제 억제제 |
| BRPI0612545A2 (pt) | 2005-06-14 | 2010-11-23 | Schering Corp | compostos inibidores de protease, composições farmacêuticas e uso dos mesmos |
| ES2572263T3 (es) | 2005-10-25 | 2016-05-31 | Shionogi & Co | Derivados de dihidrooxazina y tetrahidropirimidina como inhibidores de BACE 1 |
| CA2653650A1 (en) | 2006-06-12 | 2007-12-21 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
| EP2147914B1 (en) | 2007-04-24 | 2014-06-04 | Shionogi&Co., Ltd. | Aminodihydrothiazine derivatives substituted with cyclic groups |
| EP2151435A4 (en) | 2007-04-24 | 2011-09-14 | Shionogi & Co | PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF ALZHEIMER'S DISEASE |
| EP2283016B1 (en) | 2008-04-22 | 2014-09-24 | Merck Sharp & Dohme Corp. | Thiophenyl-substituted 2-imino-3-methyl pyrrolo pyrimidinone compounds as bace-1 inhibitors, compositions, and their use |
| KR101324426B1 (ko) | 2008-06-13 | 2013-10-31 | 시오노기세야쿠 가부시키가이샤 | β 세크레타제 저해 작용을 갖는 황 함유 복소환 유도체 |
| EP2360155A4 (en) | 2008-10-22 | 2012-06-20 | Shionogi & Co | 2-AMINOPYRIDIN-4-ON AND 2-AMINOPYRIDINE DERIVATIVE WITH BACE1-HEMDERING EFFECT |
| UA108363C2 (uk) | 2009-10-08 | 2015-04-27 | Похідні імінотіадіазиндіоксиду як інгібітори bace, композиція на їх основі і їх застосування | |
| CN102834384A (zh) | 2009-12-11 | 2012-12-19 | 盐野义制药株式会社 | *嗪衍生物 |
| US9018219B2 (en) | 2010-10-29 | 2015-04-28 | Shionogi & Co., Ltd. | Fused aminodihydropyrimidine derivative |
| WO2012057248A1 (ja) | 2010-10-29 | 2012-05-03 | 塩野義製薬株式会社 | ナフチリジン誘導体 |
| EP2694521B1 (en) | 2011-04-07 | 2015-11-25 | Merck Sharp & Dohme Corp. | Pyrrolidine-fused thiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| EP2694489B1 (en) | 2011-04-07 | 2017-09-06 | Merck Sharp & Dohme Corp. | C5-c6 oxacyclic-fused thiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
| EP2703399A4 (en) | 2011-04-26 | 2014-10-15 | Shionogi & Co | OXAZINE DERIVATIVE AND BACE-1 HEMMER THEREOF |
| JP2014524472A (ja) | 2011-08-22 | 2014-09-22 | メルク・シャープ・アンド・ドーム・コーポレーション | Ｂａｃｅ阻害剤としての２−スピロ置換イミノチアジンならびにそのモノオキシドおよびジオキシド、組成物、ならびにそれらの使用 |
| WO2014065434A1 (en) | 2012-10-24 | 2014-05-01 | Shionogi & Co., Ltd. | Dihydrooxazine or oxazepine derivatives having bace1 inhibitory activity |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MXPA06014792A (es) * | 2004-06-16 | 2007-02-16 | Wyeth Corp | Difenilimidazopirimidina y aminas imidazol como inhibidores de ??-secretasa. |
| ATE444962T1 (de) * | 2004-06-16 | 2009-10-15 | Wyeth Corp | Amino-5,5-diphenylimidazolon-derivate zur beta- sekretase-hemmung |
| BRPI0606690A2 (pt) * | 2005-01-14 | 2009-07-14 | Wyeth Corp | composto; uso do composto para o tratamento de uma doença ou distúrbio associado com uma atividade excessiva de bace; e composição farmacêutica |
| AU2006266167A1 (en) * | 2005-06-30 | 2007-01-11 | Wyeth | Amino-5-(6-membered)heteroarylimidazolone compounds and the use thereof for beta-secretase modulation |
| TW200738683A (en) * | 2005-06-30 | 2007-10-16 | Wyeth Corp | Amino-5-(5-membered)heteroarylimidazolone compounds and the use thereof for β-secretase modulation |
-
2007
- 2007-07-24 TW TW096126963A patent/TW200817406A/zh unknown
- 2007-08-07 CL CL200702288A patent/CL2007002288A1/es unknown
- 2007-08-07 PE PE2007001049A patent/PE20080744A1/es not_active Application Discontinuation
- 2007-08-10 CA CA002660441A patent/CA2660441A1/en not_active Abandoned
- 2007-08-10 JP JP2009524746A patent/JP2010500999A/ja not_active Withdrawn
- 2007-08-10 EP EP07840855A patent/EP2054414A2/en not_active Withdrawn
- 2007-08-10 MX MX2009001699A patent/MX2009001699A/es not_active Application Discontinuation
- 2007-08-10 WO PCT/US2007/075690 patent/WO2008022024A2/en active Application Filing
- 2007-08-16 AR ARP070103654A patent/AR062409A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| TW200817406A (en) | 2008-04-16 |
| EP2054414A2 (en) | 2009-05-06 |
| WO2008022024A2 (en) | 2008-02-21 |
| MX2009001699A (es) | 2009-02-25 |
| CL2007002288A1 (es) | 2008-02-08 |
| PE20080744A1 (es) | 2008-05-24 |
| AR062409A1 (es) | 2008-11-05 |
| WO2008022024A3 (en) | 2008-05-22 |
| CA2660441A1 (en) | 2008-02-21 |
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