ES2615381T3 - Nuevos benzotiofenos y benzofuranos sustituidos en la posición 2 con heteroarilo - Google Patents
Nuevos benzotiofenos y benzofuranos sustituidos en la posición 2 con heteroarilo Download PDFInfo
- Publication number
- ES2615381T3 ES2615381T3 ES08724190.7T ES08724190T ES2615381T3 ES 2615381 T3 ES2615381 T3 ES 2615381T3 ES 08724190 T ES08724190 T ES 08724190T ES 2615381 T3 ES2615381 T3 ES 2615381T3
- Authority
- ES
- Spain
- Prior art keywords
- fluoroalkyl
- benzofuran
- alkyl
- alkylene
- pyridin
- 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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- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 title description 16
- 125000001072 heteroaryl group Chemical group 0.000 title description 16
- MPNFMCAOBNNFJF-UHFFFAOYSA-N 2,3-diphenyl-1-benzofuran Chemical group C1=CC=CC=C1C1=C(C=2C=CC=CC=2)C2=CC=CC=C2O1 MPNFMCAOBNNFJF-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 237
- -1 hydroxy, methoxy Chemical group 0.000 claims abstract description 87
- 125000003709 fluoroalkyl group Chemical group 0.000 claims abstract description 67
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 47
- 125000004429 atom Chemical group 0.000 claims abstract description 44
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 43
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 40
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 33
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims abstract description 31
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 30
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 28
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 26
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 26
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 25
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims abstract description 22
- 125000001424 substituent group Chemical group 0.000 claims abstract description 19
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 16
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 14
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 12
- 229910006074 SO2NH2 Inorganic materials 0.000 claims abstract description 11
- 239000012453 solvate Substances 0.000 claims abstract description 11
- 125000000565 sulfonamide group Chemical group 0.000 claims abstract description 11
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 11
- 125000005843 halogen group Chemical group 0.000 claims abstract description 10
- 239000011630 iodine Substances 0.000 claims abstract description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 7
- 239000012458 free base Substances 0.000 claims abstract description 6
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims abstract description 6
- 239000000470 constituent Substances 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 52
- 239000000203 mixture Substances 0.000 claims description 40
- 239000002243 precursor Substances 0.000 claims description 28
- 208000037259 Amyloid Plaque Diseases 0.000 claims description 25
- 238000001727 in vivo Methods 0.000 claims description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 21
- 230000027455 binding Effects 0.000 claims description 17
- 238000001514 detection method Methods 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
- 206010002022 amyloidosis Diseases 0.000 claims description 9
- MYNQXTDIPMCJCR-UHFFFAOYSA-N 2-[2-fluoro-6-(methylamino)pyridin-3-yl]-1-benzofuran-5-ol Chemical compound FC1=NC(NC)=CC=C1C1=CC2=CC(O)=CC=C2O1 MYNQXTDIPMCJCR-UHFFFAOYSA-N 0.000 claims description 8
- 125000000524 functional group Chemical group 0.000 claims description 8
- PQCXZHFSSVHSPI-UHFFFAOYSA-N 2-[5-fluoro-6-(methylamino)pyridin-3-yl]-1-benzofuran-5-ol Chemical compound C1=C(F)C(NC)=NC=C1C1=CC2=CC(O)=CC=C2O1 PQCXZHFSSVHSPI-UHFFFAOYSA-N 0.000 claims description 7
- FXERARHKNULYEN-UHFFFAOYSA-N 2-[6-fluoro-5-(methylamino)pyridin-2-yl]-1-benzofuran-5-ol Chemical compound N1=C(F)C(NC)=CC=C1C1=CC2=CC(O)=CC=C2O1 FXERARHKNULYEN-UHFFFAOYSA-N 0.000 claims description 7
- PHXURHLWZKMNQW-UHFFFAOYSA-N 5-(5-methoxy-1-benzofuran-2-yl)-n-methylpyridin-2-amine Chemical compound C1=NC(NC)=CC=C1C1=CC2=CC(OC)=CC=C2O1 PHXURHLWZKMNQW-UHFFFAOYSA-N 0.000 claims description 7
- 239000003550 marker Substances 0.000 claims description 7
- 238000004611 spectroscopical analysis Methods 0.000 claims description 7
- IJQFRKSVILYZED-UHFFFAOYSA-N 2-(6-aminopyridazin-3-yl)-1-benzofuran-5-ol Chemical compound N1=NC(N)=CC=C1C1=CC2=CC(O)=CC=C2O1 IJQFRKSVILYZED-UHFFFAOYSA-N 0.000 claims description 6
- YOQRASPYXLBVOK-UHFFFAOYSA-N 2-[6-(methylamino)pyridin-3-yl]-1-benzofuran-5-ol Chemical compound C1=NC(NC)=CC=C1C1=CC2=CC(O)=CC=C2O1 YOQRASPYXLBVOK-UHFFFAOYSA-N 0.000 claims description 6
- PAAHSWQSYPOWCP-UHFFFAOYSA-N 6-(5-methoxy-1-benzofuran-2-yl)pyridazin-3-amine Chemical compound C=1C2=CC(OC)=CC=C2OC=1C1=CC=C(N)N=N1 PAAHSWQSYPOWCP-UHFFFAOYSA-N 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- NXKHCMJNTQJOCQ-UHFFFAOYSA-N 6-fluoro-5-(5-methoxy-1-benzofuran-2-yl)pyridin-2-amine Chemical compound C=1C2=CC(OC)=CC=C2OC=1C1=CC=C(N)N=C1F NXKHCMJNTQJOCQ-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- ATYMSVHLRZYFFH-UHFFFAOYSA-N 2-(1-benzofuran-2-yl)-6-methoxyimidazo[1,2-a]pyridine Chemical compound C1=CC=C2OC(C=3N=C4C=CC(=CN4C=3)OC)=CC2=C1 ATYMSVHLRZYFFH-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- 238000003325 tomography Methods 0.000 claims description 3
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 150000002496 iodine Chemical class 0.000 claims description 2
- 125000001209 o-nitrophenyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])[N+]([O-])=O 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 abstract description 26
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 89
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 40
- 235000019439 ethyl acetate Nutrition 0.000 description 37
- 238000005481 NMR spectroscopy Methods 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- 239000000243 solution Substances 0.000 description 27
- 239000007787 solid Substances 0.000 description 26
- 208000024827 Alzheimer disease Diseases 0.000 description 25
- 229910001868 water Inorganic materials 0.000 description 25
- 239000000543 intermediate Substances 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- 210000004556 brain Anatomy 0.000 description 21
- 238000002360 preparation method Methods 0.000 description 21
- 239000002904 solvent Substances 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- 238000011282 treatment Methods 0.000 description 18
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 17
- 125000006239 protecting group Chemical group 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 14
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 14
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 239000007832 Na2SO4 Substances 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 13
- 229910052938 sodium sulfate Inorganic materials 0.000 description 13
- 235000011152 sodium sulphate Nutrition 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
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- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000011534 wash buffer Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Hospice & Palliative Care (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Furan Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US89314907P | 2007-03-06 | 2007-03-06 | |
| US893149P | 2007-03-06 | ||
| PCT/SE2008/050243 WO2008108730A1 (en) | 2007-03-06 | 2008-03-05 | Novel 2-heteroaryl substituted benzothiophenes and benzofuranes 709 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2615381T3 true ES2615381T3 (es) | 2017-06-06 |
Family
ID=39738510
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES08724190.7T Active ES2615381T3 (es) | 2007-03-06 | 2008-03-05 | Nuevos benzotiofenos y benzofuranos sustituidos en la posición 2 con heteroarilo |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US7772256B2 (https=) |
| EP (1) | EP2132201B1 (https=) |
| JP (1) | JP5631009B2 (https=) |
| KR (1) | KR101530392B1 (https=) |
| CN (2) | CN102617556A (https=) |
| AR (1) | AR065599A1 (https=) |
| AU (1) | AU2008221668B2 (https=) |
| BR (1) | BRPI0808503B8 (https=) |
| CA (1) | CA2680157C (https=) |
| CL (1) | CL2008000645A1 (https=) |
| CO (1) | CO6220965A2 (https=) |
| EC (1) | ECSP099641A (https=) |
| ES (1) | ES2615381T3 (https=) |
| IL (1) | IL200524A0 (https=) |
| MX (1) | MX2009009469A (https=) |
| MY (1) | MY147347A (https=) |
| NZ (1) | NZ579157A (https=) |
| PE (1) | PE20090164A1 (https=) |
| SA (1) | SA08290097B1 (https=) |
| TW (1) | TW200901998A (https=) |
| UA (1) | UA98481C2 (https=) |
| UY (1) | UY30951A1 (https=) |
| WO (1) | WO2008108730A1 (https=) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW200901998A (en) * | 2007-03-06 | 2009-01-16 | Astrazeneca Ab | Novel 2-heteroaryl substituted benzothiophenes and benzofuranes |
| CA2725940A1 (en) | 2008-05-30 | 2009-12-23 | Merck Sharp & Dohme Corp. | Novel substituted azabenzoxazoles |
| NZ590688A (en) | 2008-08-05 | 2012-09-28 | Daiichi Sankyo Co Ltd | imidazo[4,5-b]pyridin-2-one derivatives |
| US8193363B2 (en) * | 2008-08-29 | 2012-06-05 | Astrazeneca Ab | Compounds suitable as precursors to compounds that are useful for imaging amyloid deposits |
| KR101123178B1 (ko) * | 2009-04-09 | 2012-06-13 | (주)에스메디 | 2-아릴벤조싸이오펜 유도체 또는 이의 약학적으로 허용가능한 염, 이의 제조방법 및 이를 유효성분으로 함유하는 퇴행성 뇌질환의 진단 또는 치료용 약학적 조성물 |
| WO2011059080A1 (ja) * | 2009-11-16 | 2011-05-19 | 第一三共株式会社 | 同位体置換されたジアミン誘導体 |
| EP2388255A1 (en) * | 2010-05-11 | 2011-11-23 | Ikerchem, S.L. | Polysubstituted benzofurans and medicinal applications thereof |
| WO2012017891A1 (ja) * | 2010-08-06 | 2012-02-09 | 国立大学法人京都大学 | ピリジルベンゾフラン誘導体 |
| WO2019149965A1 (en) * | 2018-02-05 | 2019-08-08 | Universite De Strasbourg | Compounds and compositions for the treatment of pain |
| KR20220044721A (ko) * | 2019-08-06 | 2022-04-11 | 도메인 테라퓨틱스 | 신경펩타이드 ff 수용체 길항제로서의 5-헤테로아릴-피리딘-2-아민 화합물 |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU523040B2 (en) | 1978-05-15 | 1982-07-08 | Kanebo Limited | Calcium -antagonistic composition |
| GB8305245D0 (en) | 1983-02-25 | 1983-03-30 | Fujisawa Pharmaceutical Co | Imidazo-heterocyclic compounds |
| CA2034309C (en) | 1990-01-22 | 1997-04-01 | Takashi Iwaki | Mesomorphic compound, liquid crystal composition containing same, liquid crystal device using same and display apparatus |
| WO1995017095A1 (en) * | 1993-12-21 | 1995-06-29 | Eli Lilly And Company | Methods for the treatment or prevention of conditions associated with amyloidogenic reptides |
| US5518713A (en) | 1995-02-13 | 1996-05-21 | 3V Inc. | Benzoxazole derivatives, the use thereof as sunscreens and cosmetic compositions containing them |
| JPH11116476A (ja) | 1997-10-16 | 1999-04-27 | Sankyo Co Ltd | 縮合複素環化合物 |
| PT1334091E (pt) | 2000-08-24 | 2013-01-07 | Univ Pittsburgh | Derivados de tioflavina e seu uso no diagnóstico e terapia da doença de alzheimer |
| EP1345914A1 (en) | 2000-12-22 | 2003-09-24 | AstraZeneca AB | Therapeutic compounds |
| WO2002055496A1 (en) * | 2001-01-15 | 2002-07-18 | Glaxo Group Limited | Aryl piperidine and piperazine derivatives as inducers of ldl-receptor expression |
| JP4307001B2 (ja) * | 2001-03-14 | 2009-08-05 | キヤノン株式会社 | 金属配位化合物、電界発光素子及び表示装置 |
| US6596731B2 (en) | 2001-03-27 | 2003-07-22 | Hoffmann-La Roche Inc. | Substituted imidazo[1,2-A] pyridine derivatives |
| WO2002085903A2 (en) | 2001-04-23 | 2002-10-31 | The Trustees Of The University Of Pennsylvania | Amyloid plaque aggregation inhibitors and diagnostic imaging agents |
| AU2002349477A1 (en) | 2001-11-26 | 2003-06-10 | Takeda Chemical Industries, Ltd. | Bicyclic derivative, process for producing the same, and use |
| GB0130305D0 (en) * | 2001-12-19 | 2002-02-06 | Amersham Plc | Compounds for imaging alzheimers disease |
| AU2003242233A1 (en) | 2002-06-12 | 2003-12-31 | Bf Research Institute, Inc. | Probe compound for image diagnosis of disease with amyloid accumulation, compound for staining age spots/diffuse age spots, and remedy for disease with amyloid accumulation |
| TW200401194A (en) | 2002-07-11 | 2004-01-16 | Advanced Micro Devices Inc | Method and apparatus for determining a processor state without interrupting processor operation |
| ATE425753T1 (de) | 2002-08-02 | 2009-04-15 | Genesoft Pharmaceuticals Inc | Biaryl-verbindungen mit antiinfektiver wirkung |
| JP2004250411A (ja) | 2003-02-21 | 2004-09-09 | Bf Kenkyusho:Kk | アミロイドβ蓄積性疾患の診断プローブおよび治療用化合物 |
| CA2438032C (en) | 2003-03-14 | 2013-05-07 | University Of Pittsburgh | Benzothiazole derivative compounds, compositions and uses |
| JPWO2004087641A1 (ja) | 2003-03-31 | 2006-06-29 | 第一製薬株式会社 | ヒドラゾン誘導体 |
| AU2004238508B2 (en) | 2003-05-13 | 2009-11-19 | F. Hoffmann-La Roche Ag | Imidazo-benzothiazoles |
| CA2530389A1 (en) * | 2003-07-02 | 2005-01-13 | Biofocus Discovery Limited | Pyrazine and pyridine derivatives as rho kinase inhibitors |
| GB0420722D0 (en) | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
| EP1893576A4 (en) | 2005-05-27 | 2010-03-17 | Univ Kingston | TREATMENT OF PROTEIN DISORDERING |
| RU2499795C2 (ru) * | 2005-07-04 | 2013-11-27 | Хай Пойнт Фармасьютикалс, ЛЛС | Антагонисты гистаминовых н3-рецепторов |
| WO2007033080A2 (en) | 2005-09-12 | 2007-03-22 | Emory University | Alzheimer's disease imaging agents |
| JP2009508863A (ja) | 2005-09-16 | 2009-03-05 | ユニバーシティー オブ ピッツバーグ | 少なくとも１種のアミロイド形成タンパク質を含むアミロイド沈着物を検出するためのｉｎｖｉｖｏまたはｉｎｖｉｔｒｏ方法 |
| WO2007047204A1 (en) | 2005-10-11 | 2007-04-26 | University Of Pittsburgh | Isotopically-labeled benzofuran compounds as imagingagents foramyloidogenic proteins |
| EP1956013B1 (en) | 2005-11-30 | 2016-04-13 | Fujifilm RI Pharma Co., Ltd. | Diagnostic and remedy for disease caused by amyloid aggregation and/or deposition |
| TW200736252A (en) | 2006-01-27 | 2007-10-01 | Astrazeneca Ab | Novel heteroaryl substituted benzothiazoles |
| US7700616B2 (en) | 2006-05-08 | 2010-04-20 | Molecular Neuroimaging, Llc. | Compounds and amyloid probes thereof for therapeutic and imaging uses |
| TW200813035A (en) | 2006-06-19 | 2008-03-16 | Astrazeneca Ab | Novel heteroaryl substituted benzoxazoles |
| EP2125800A1 (en) | 2007-01-22 | 2009-12-02 | AstraZeneca AB | Novel heteroaryl substituted imidazo ý1,2 -a¨pyridine derivatives |
| TW200901998A (en) * | 2007-03-06 | 2009-01-16 | Astrazeneca Ab | Novel 2-heteroaryl substituted benzothiophenes and benzofuranes |
-
2008
- 2008-03-03 TW TW097107378A patent/TW200901998A/zh unknown
- 2008-03-04 SA SA8290097A patent/SA08290097B1/ar unknown
- 2008-03-04 CL CL200800645A patent/CL2008000645A1/es unknown
- 2008-03-05 NZ NZ579157A patent/NZ579157A/en not_active IP Right Cessation
- 2008-03-05 KR KR1020097018603A patent/KR101530392B1/ko active Active
- 2008-03-05 AR ARP080100905A patent/AR065599A1/es active IP Right Grant
- 2008-03-05 CA CA2680157A patent/CA2680157C/en active Active
- 2008-03-05 MX MX2009009469A patent/MX2009009469A/es active IP Right Grant
- 2008-03-05 JP JP2009552641A patent/JP5631009B2/ja active Active
- 2008-03-05 US US12/042,795 patent/US7772256B2/en active Active
- 2008-03-05 CN CN2012100933476A patent/CN102617556A/zh active Pending
- 2008-03-05 UY UY30951A patent/UY30951A1/es not_active Application Discontinuation
- 2008-03-05 EP EP08724190.7A patent/EP2132201B1/en active Active
- 2008-03-05 MY MYPI20093695A patent/MY147347A/en unknown
- 2008-03-05 AU AU2008221668A patent/AU2008221668B2/en active Active
- 2008-03-05 BR BRPI0808503A patent/BRPI0808503B8/pt active IP Right Grant
- 2008-03-05 PE PE2008000429A patent/PE20090164A1/es not_active Application Discontinuation
- 2008-03-05 WO PCT/SE2008/050243 patent/WO2008108730A1/en not_active Ceased
- 2008-03-05 CN CN2008800149945A patent/CN101675042B/zh active Active
- 2008-03-05 ES ES08724190.7T patent/ES2615381T3/es active Active
- 2008-05-03 UA UAA200908596A patent/UA98481C2/ru unknown
-
2009
- 2009-08-20 IL IL200524A patent/IL200524A0/en unknown
- 2009-09-07 CO CO09095235A patent/CO6220965A2/es not_active Application Discontinuation
- 2009-09-21 EC EC2009009641A patent/ECSP099641A/es unknown
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