JP5128956B2 - アミロイドプラークに結合し画像化するためのスチルベン誘導体及びそれらの使用 - Google Patents
アミロイドプラークに結合し画像化するためのスチルベン誘導体及びそれらの使用 Download PDFInfo
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- JP5128956B2 JP5128956B2 JP2007546948A JP2007546948A JP5128956B2 JP 5128956 B2 JP5128956 B2 JP 5128956B2 JP 2007546948 A JP2007546948 A JP 2007546948A JP 2007546948 A JP2007546948 A JP 2007546948A JP 5128956 B2 JP5128956 B2 JP 5128956B2
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- Prior art keywords
- ethoxy
- compound
- phenyl
- alkyl
- hydroxy
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- 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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- 208000037259 Amyloid Plaque Diseases 0.000 title claims description 38
- 238000003384 imaging method Methods 0.000 title claims description 16
- PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical class C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 title description 49
- 230000027455 binding Effects 0.000 title description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 136
- 150000001875 compounds Chemical class 0.000 claims description 120
- 238000000034 method Methods 0.000 claims description 52
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- -1 R 31 Chemical compound 0.000 claims description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 39
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 33
- 150000002431 hydrogen Chemical class 0.000 claims description 28
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
- 125000004104 aryloxy group Chemical class 0.000 claims description 9
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- ONPMSDSSDFXXIH-UHFFFAOYSA-N 2-[2-[2-[2-[2-[4-[2-[4-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]phenyl]ethenyl]phenoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl methanesulfonate Chemical compound C(C)(C)(C)OC(=O)N(C1=CC=C(C=C1)C=CC1=CC=C(OCCOCCOCCOCCOCCOS(=O)(=O)C)C=C1)C ONPMSDSSDFXXIH-UHFFFAOYSA-N 0.000 claims description 5
- SLFUMHVONHXTGT-UHFFFAOYSA-N 2-[2-[4-[2-[4-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]phenyl]ethenyl]phenoxy]ethoxy]ethyl methanesulfonate Chemical compound C1=CC(N(C(=O)OC(C)(C)C)C)=CC=C1C=CC1=CC=C(OCCOCCOS(C)(=O)=O)C=C1 SLFUMHVONHXTGT-UHFFFAOYSA-N 0.000 claims description 5
- 230000002776 aggregation Effects 0.000 claims description 5
- 238000004220 aggregation Methods 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- GQRCCPYYDNJGRB-UHFFFAOYSA-N tert-butyl n-[4-[2-[4-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]phenyl]ethenyl]phenyl]-n-methylcarbamate Chemical compound C1=CC(N(C(=O)OC(C)(C)C)C)=CC=C1C=CC1=CC=C(OCCOCCOCCOCCOCCO)C=C1 GQRCCPYYDNJGRB-UHFFFAOYSA-N 0.000 claims description 5
- OKILIKAZGFFFSO-UHFFFAOYSA-N 2-[2-[2-[2-[4-[2-[4-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]phenyl]ethenyl]phenoxy]ethoxy]ethoxy]ethoxy]ethyl methanesulfonate Chemical compound C1=CC(N(C(=O)OC(C)(C)C)C)=CC=C1C=CC1=CC=C(OCCOCCOCCOCCOS(C)(=O)=O)C=C1 OKILIKAZGFFFSO-UHFFFAOYSA-N 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- UWPGGJPPQYTXTB-UHFFFAOYSA-N tert-butyl n-[4-[2-[4-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]phenyl]ethenyl]phenyl]-n-methylcarbamate Chemical compound C1=CC(N(C(=O)OC(C)(C)C)C)=CC=C1C=CC1=CC=C(OCCOCCOCCO)C=C1 UWPGGJPPQYTXTB-UHFFFAOYSA-N 0.000 claims description 4
- ARPAIIPQVISPDE-UHFFFAOYSA-N tert-butyl n-[4-[2-[4-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]phenyl]ethenyl]phenyl]-n-methylcarbamate Chemical compound C1=CC(N(C(=O)OC(C)(C)C)C)=CC=C1C=CC1=CC=C(OCCOCCOCCOCCO)C=C1 ARPAIIPQVISPDE-UHFFFAOYSA-N 0.000 claims description 4
- AUFVJZSDSXXFOI-UHFFFAOYSA-N 2.2.2-cryptand Chemical compound C1COCCOCCN2CCOCCOCCN1CCOCCOCC2 AUFVJZSDSXXFOI-UHFFFAOYSA-N 0.000 claims description 3
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- LNBJHFMIERDXJJ-UHFFFAOYSA-N 2-[2-[2-[4-[2-[4-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]phenyl]ethenyl]phenoxy]ethoxy]ethoxy]ethyl methanesulfonate Chemical compound C1=CC(N(C(=O)OC(C)(C)C)C)=CC=C1C=CC1=CC=C(OCCOCCOCCOS(C)(=O)=O)C=C1 LNBJHFMIERDXJJ-UHFFFAOYSA-N 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 49
- 208000024827 Alzheimer disease Diseases 0.000 description 40
- 210000004556 brain Anatomy 0.000 description 33
- 239000000243 solution Substances 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- PJANXHGTPQOBST-VAWYXSNFSA-N Stilbene Natural products C=1C=CC=CC=1/C=C/C1=CC=CC=C1 PJANXHGTPQOBST-VAWYXSNFSA-N 0.000 description 19
- 235000021286 stilbenes Nutrition 0.000 description 19
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 18
- 210000001519 tissue Anatomy 0.000 description 17
- 150000003839 salts Chemical class 0.000 description 15
- 229910052731 fluorine Inorganic materials 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000002202 Polyethylene glycol Substances 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 229920001223 polyethylene glycol Polymers 0.000 description 11
- 238000012746 preparative thin layer chromatography Methods 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000002243 precursor Substances 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 239000011737 fluorine Substances 0.000 description 8
- 229910052736 halogen Inorganic materials 0.000 description 8
- 150000002367 halogens Chemical class 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 239000003446 ligand Substances 0.000 description 8
- 230000014759 maintenance of location Effects 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 7
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 238000011888 autopsy Methods 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 125000003282 alkyl amino group Chemical group 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 6
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 5
- ZQAQXZBSGZUUNL-BJUDXGSMSA-N 2-[4-(methylamino)phenyl]-1,3-benzothiazol-6-ol Chemical compound C1=CC(N[11CH3])=CC=C1C1=NC2=CC=C(O)C=C2S1 ZQAQXZBSGZUUNL-BJUDXGSMSA-N 0.000 description 5
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 5
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 5
- HPKJGHVHQWJOOT-ZJOUEHCJSA-N N-[(2S)-3-cyclohexyl-1-oxo-1-({(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl}amino)propan-2-yl]-1H-indole-2-carboxamide Chemical compound C1C(CCCC1)C[C@H](NC(=O)C=1NC2=CC=CC=C2C=1)C(=O)N[C@@H](C[C@H]1C(=O)NCC1)C=O HPKJGHVHQWJOOT-ZJOUEHCJSA-N 0.000 description 5
- 230000003941 amyloidogenesis Effects 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 210000003710 cerebral cortex Anatomy 0.000 description 5
- 238000003745 diagnosis Methods 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 125000000623 heterocyclic group Chemical group 0.000 description 5
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
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- MWDVCHRYCKXEBY-LBPRGKRZSA-N 3-chloro-n-[2-oxo-2-[[(1s)-1-phenylethyl]amino]ethyl]benzamide Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(=O)CNC(=O)C1=CC=CC(Cl)=C1 MWDVCHRYCKXEBY-LBPRGKRZSA-N 0.000 description 4
- DNXLZTGRZRGRQX-UHFFFAOYSA-N 4-[2-[4-[2-(2-fluoroethoxy)ethoxy]phenyl]ethenyl]-n-methylaniline Chemical compound C1=CC(NC)=CC=C1C=CC1=CC=C(OCCOCCF)C=C1 DNXLZTGRZRGRQX-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- TYYCNSUODPEVQP-UHFFFAOYSA-N 8-[(4-fluorophenyl)sulfonylamino]-4-(3-pyridin-3-ylpropyl)octanoic acid Chemical compound C=1C=CN=CC=1CCCC(CCC(=O)O)CCCCNS(=O)(=O)C1=CC=C(F)C=C1 TYYCNSUODPEVQP-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
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- 239000012359 Methanesulfonyl chloride Substances 0.000 description 4
- XFFSCOOTVXBLCK-QAVVBOBSSA-N OC(=O)c1cc(ccc1O)\N=N\c1ccc(cc1)-c1ccc(cc1)\N=N\c1ccc(O)c(c1)C(O)=O Chemical compound OC(=O)c1cc(ccc1O)\N=N\c1ccc(cc1)-c1ccc(cc1)\N=N\c1ccc(O)c(c1)C(O)=O XFFSCOOTVXBLCK-QAVVBOBSSA-N 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
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- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 4
- 125000001153 fluoro group Chemical group F* 0.000 description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 4
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
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- 230000007170 pathology Effects 0.000 description 4
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- 238000010898 silica gel chromatography Methods 0.000 description 4
- DVWOYOSIEJRHKW-UIRZNSHLSA-M sodium (2S)-2-[[(2S)-2-[[(4,4-difluorocyclohexyl)-phenylmethoxy]carbonylamino]-4-methylpentanoyl]amino]-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonate Chemical compound FC1(CCC(CC1)C(OC(=O)N[C@H](C(=O)N[C@H](C(S(=O)(=O)[O-])O)C[C@H]1C(NCC1)=O)CC(C)C)C1=CC=CC=C1)F.[Na+] DVWOYOSIEJRHKW-UIRZNSHLSA-M 0.000 description 4
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- 125000001544 thienyl group Chemical group 0.000 description 4
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- C07C15/02—Monocyclic hydrocarbons
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- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/78—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C217/80—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
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- 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
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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- C07B59/001—Acyclic or carbocyclic compounds
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| US63669604P | 2004-12-17 | 2004-12-17 | |
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| US68639505P | 2005-06-02 | 2005-06-02 | |
| US60/686,395 | 2005-06-02 | ||
| PCT/US2005/045682 WO2006066104A2 (en) | 2004-12-17 | 2005-12-19 | Stilbene derivatives and their use for binding and imaging amyloid plaques |
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| JP2008524243A JP2008524243A (ja) | 2008-07-10 |
| JP5128956B2 true JP5128956B2 (ja) | 2013-01-23 |
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| CA2456411C (en) * | 2001-08-27 | 2011-02-15 | The Trustees Of The University Of Pennsylvania | Stilbene derivatives and their use for binding and imaging amyloid plaques |
| CA2591534C (en) * | 2004-12-17 | 2013-08-06 | The Trustees Of The University Of Pennsylvania | Stilbene derivatives and their use for binding and imaging amyloid plaques |
| WO2006078384A2 (en) * | 2004-12-17 | 2006-07-27 | The Trustees Of The University Of Pennsylvania | Stilbene derivatives and their use |
| EP1893245A4 (en) * | 2005-06-24 | 2009-06-24 | Univ Pennsylvania | RADIOMARQUE PEGYLATION OF LIGANDS FOR USE AS IMAGING AGENTS |
| DK1999109T3 (da) * | 2006-03-30 | 2012-04-02 | Univ Pennsylvania | Styrylpyridinderivater og anvendelse heraf til binding og billeddannelse af amyloidplaques |
| US20080253967A1 (en) * | 2007-04-13 | 2008-10-16 | Kung Hank F | Halo-Stilbene Derivatives And Their Use For Binding And Imaging Of Amyloid Plaques |
| WO2009001046A2 (en) * | 2007-06-22 | 2008-12-31 | The University Court Of The University Of Aberdeen | [11c]methoxy-radiolabelled 2,3',4,5'-tetramethylstilbene (tms) and its preparation and use |
| US20100272642A1 (en) * | 2007-07-04 | 2010-10-28 | Tohoku University | Pet probe having an alkoxy group substituted by fluorine and hydroxy group |
| ES2552764T3 (es) * | 2007-10-15 | 2015-12-02 | The Salk Institute For Biological Studies | Métodos para el tratamiento de varias enfermedades y afecciones, y compuestos útiles para los mismos |
| US8932557B2 (en) | 2008-02-14 | 2015-01-13 | Eli Lilly And Company | Imaging agents for detecting neurological dysfunction |
| US20110046378A1 (en) * | 2008-02-14 | 2011-02-24 | Siemens Medical Solutions Usa, Inc. | Novel Imaging Agents for Detecting Neurological Dysfunction |
| EP2247944A1 (en) * | 2008-02-27 | 2010-11-10 | Avid Radiopharmaceuticals, Inc. | Gamma probe detection of amyloid plaque using radiolabeled a-beta binding compounds |
| JP5603855B2 (ja) | 2008-04-04 | 2014-10-08 | アビッド レディオファーマシューティカルズ、インク． | 神経変成疾患の放射性薬剤による画像化 |
| JP2012508889A (ja) * | 2008-11-13 | 2012-04-12 | アビッド レディオファーマシューティカルズ、インク． | 神経変性疾患の検出と診断のためのヒストグラムに基づいた分析方法 |
| EP2379757A2 (en) * | 2008-12-22 | 2011-10-26 | Bayer Pharma Aktiengesellschaft | A method for the synthesis of a radionuclide-labeled compound |
| US20100172836A1 (en) * | 2008-12-31 | 2010-07-08 | Avid Radiopharmaceuticals, Inc. | Synthesis of 18f-radiolabeled styrylpyridines from tosylate precursors and stable pharmaceutical compositions thereof |
| CU23844B1 (es) | 2009-04-17 | 2012-10-15 | Ct De Neurociencias De Cuba | Procedimiento de obtención de nuevos derivados de naftaleno para el diagnóstico in vivo de la enfermedad de alzheimer |
| CA2767475A1 (en) * | 2009-07-10 | 2011-01-13 | Bayer Pharma Aktiengesellschaft | Usage of low to medium-pressure liquid chromatography for the purification of radiotracers |
| KR20120098914A (ko) * | 2009-12-23 | 2012-09-05 | 피라말 이미징 에스에이 | 소수성 ｐｅｔ 작용제를 갖는 ｐｅｔ 영상화에 적합한 제제 |
| MX2012014115A (es) | 2010-06-04 | 2013-07-03 | Piramal Imaging Sa | Metodo para la produccion de ligandos beta amiloide marcados con 18f. |
| TWI504414B (zh) | 2010-06-04 | 2015-10-21 | Bayer Schering Pharma Ag | 生產Ｆ－１８標記之Ａβ配位體之方法 |
| EA201201647A1 (ru) | 2010-06-04 | 2013-05-30 | Пирамаль Имэджинг Са | Способ получения f-18 меченных лигандов бета-амилоида |
| LT2579902T (lt) * | 2010-06-04 | 2017-09-25 | Piramal Imaging Sa | Gamybos būdas amiloido beta ligandų, žymėtų f-18 |
| WO2012051170A2 (en) * | 2010-10-12 | 2012-04-19 | Mayo Foundation For Medical Education And Research | Imaging of meningiomas using phingylbenzothiazole, stilbene, or biphenylalkyne derivatives |
| KR20140012732A (ko) * | 2011-04-21 | 2014-02-03 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | 작용화된 자성 나노입자, 그리고 아밀로이드 침착물 및 신경섬유매듭의 영상화에서의 용도 |
| WO2012175641A1 (en) * | 2011-06-21 | 2012-12-27 | Piramal Imaging Sa | Formulations of fluorinated stilbene suitable for pet imaging |
| KR101291037B1 (ko) * | 2011-10-12 | 2013-08-01 | 사회복지법인 삼성생명공익재단 | 레스베라트롤 유도체와 스티릴-오각형 방향족 화합물 및 이들의 베타-아밀로이드 플라그에 대한 결합제 및 진단영상제의 용도 |
| RU2477726C1 (ru) * | 2011-10-18 | 2013-03-20 | Общество С Ограниченной Ответственностью "Ньювак" (Ооо "Ньювак") | Замещенные феноксиуксусные кислоты, их эфиры и амиды, включающие 2,6-диоксо-2,3,6,7-тетрагидро-1н-пурин-8-иловый фрагмент, - антагонисты аденозинового a2a рецептора и их применение |
| IN2014MN00875A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2011-10-19 | 2015-04-17 | Piramal Imaging Sa | |
| KR101930124B1 (ko) | 2012-04-10 | 2018-12-17 | 랜티우스 메디컬 이메징, 인크. | 방사성제약 합성 방법 |
| US9180212B2 (en) * | 2012-05-22 | 2015-11-10 | The Regents Of The University Of California | β-amyloid plaque imaging agents |
| CU20130027A7 (es) | 2013-02-28 | 2014-10-30 | Ct De Neurociencias De Cuba | Chaperoninas químicas como nuevos moduladores moleculares de la beta agregación proteica presente en las enfermedades conformacionales |
| JP2014218454A (ja) * | 2013-05-07 | 2014-11-20 | 日本メジフィジックス株式会社 | スチリルピリジン誘導体化合物 |
| JP6041751B2 (ja) * | 2013-05-07 | 2016-12-14 | 日本メジフィジックス株式会社 | スチリルピリジン誘導体化合物 |
| KR101891404B1 (ko) * | 2015-12-18 | 2018-08-24 | 주식회사 엘지화학 | 변성 단량체, 이를 포함하는 변성 중합체 및 이들의 제조방법 |
| US10675365B2 (en) | 2016-09-29 | 2020-06-09 | Korea Atomic Energy Research Institute | Curcumin derivative, method for producing same, and photo-acoustic imaging agent comprising same for detecting beta-amyloid plaque |
| JOP20190077A1 (ar) | 2016-10-10 | 2019-04-09 | Array Biopharma Inc | مركبات بيرازولو [1، 5-a]بيريدين بها استبدال كمثبطات كيناز ret |
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| US4500507A (en) * | 1981-10-30 | 1985-02-19 | Wong Dennis W | Diagnostic composition for radiologic imaging of neoplasms in the body and method of preparation |
| JPS60247244A (ja) * | 1984-05-22 | 1985-12-06 | Mitsubishi Paper Mills Ltd | 電子写真感光体 |
| DD234666A1 (de) | 1984-11-01 | 1986-04-09 | Univ Leipzig | Verfahren zur herstellung von einfachen und substituierten 4-dimethylamino-alpha-halogenstilbenen |
| DD231432A1 (de) * | 1984-11-01 | 1985-12-24 | Univ Leipzig | Material zur silberfreien bildaufzeichnung |
| JPH06329566A (ja) | 1993-05-21 | 1994-11-29 | Asahi Glass Co Ltd | ジフルオロスチルベン誘導体化合物およびそれを含有する液晶組成物 |
| TW325458B (en) | 1993-09-08 | 1998-01-21 | Ajinomoto Kk | Stilbene derivatives and pharmaceutical compositions comprising the same for anti-cancer |
| US5601801A (en) | 1994-08-02 | 1997-02-11 | Merck Frosst Canada, Inc. | Radiolabelled angiotensin converting enzyme inhibitors |
| US5521213A (en) | 1994-08-29 | 1996-05-28 | Merck Frosst Canada, Inc. | Diaryl bicyclic heterocycles as inhibitors of cyclooxygenase-2 |
| JP4022951B2 (ja) | 1997-08-06 | 2007-12-19 | 大日本インキ化学工業株式会社 | ジフルオロスチルベン誘導体の製造方法 |
| AU5822301A (en) * | 2000-05-08 | 2001-11-20 | Novozymes A/S | Oxidoreductase mediated antimicrobial activity |
| CA2456411C (en) * | 2001-08-27 | 2011-02-15 | The Trustees Of The University Of Pennsylvania | Stilbene derivatives and their use for binding and imaging amyloid plaques |
| KR100789847B1 (ko) * | 2004-12-15 | 2007-12-28 | (주)퓨쳐켐 | 알코올 용매하에서 유기플루오로 화합물의 제조방법 |
| CA2591534C (en) * | 2004-12-17 | 2013-08-06 | The Trustees Of The University Of Pennsylvania | Stilbene derivatives and their use for binding and imaging amyloid plaques |
| WO2006078384A2 (en) | 2004-12-17 | 2006-07-27 | The Trustees Of The University Of Pennsylvania | Stilbene derivatives and their use |
| EP1893245A4 (en) * | 2005-06-24 | 2009-06-24 | Univ Pennsylvania | RADIOMARQUE PEGYLATION OF LIGANDS FOR USE AS IMAGING AGENTS |
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