HUE032660T2 - Sztirilpiridin-származékok és azok alkalmazása amiloid plakkok megkötésére és leképezésére - Google Patents
Sztirilpiridin-származékok és azok alkalmazása amiloid plakkok megkötésére és leképezésére Download PDFInfo
- Publication number
- HUE032660T2 HUE032660T2 HUE11152124A HUE11152124A HUE032660T2 HU E032660 T2 HUE032660 T2 HU E032660T2 HU E11152124 A HUE11152124 A HU E11152124A HU E11152124 A HUE11152124 A HU E11152124A HU E032660 T2 HUE032660 T2 HU E032660T2
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- HU
- Hungary
- Prior art keywords
- compound
- alkyl
- mmol
- compounds
- hydroxy
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- 208000037259 Amyloid Plaque Diseases 0.000 title claims description 47
- 238000003384 imaging method Methods 0.000 title claims description 28
- 230000027455 binding Effects 0.000 title claims description 14
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- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 45
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- 235000011181 potassium carbonates Nutrition 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000004845 protein aggregation Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000012217 radiopharmaceutical Substances 0.000 description 1
- 229940121896 radiopharmaceutical Drugs 0.000 description 1
- 230000002799 radiopharmaceutical effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- TZSZZENYCISATO-WIOPSUGQSA-N rodatristat Chemical compound CCOC(=O)[C@@H]1CC2(CN1)CCN(CC2)c1cc(O[C@H](c2ccc(Cl)cc2-c2ccccc2)C(F)(F)F)nc(N)n1 TZSZZENYCISATO-WIOPSUGQSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 208000008864 scrapie Diseases 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 235000021286 stilbenes Nutrition 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- FRACPXUHUTXLCX-BELIEFIBSA-N tert-butyl N-{1-[(1S)-1-{[(1R,2S)-1-(benzylcarbamoyl)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]carbamoyl}-2-cyclopropylethyl]-2-oxopyridin-3-yl}carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CN(C1=O)[C@@H](CC2CC2)C(=O)N[C@@H](C[C@@H]3CCNC3=O)[C@H](C(=O)NCC4=CC=CC=C4)O FRACPXUHUTXLCX-BELIEFIBSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 238000007070 tosylation reaction Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- REDSKZBUUUQMSK-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC.CCCC[Sn](CCCC)CCCC REDSKZBUUUQMSK-UHFFFAOYSA-N 0.000 description 1
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
- JSPLKZUTYZBBKA-UHFFFAOYSA-N trioxidane Chemical class OOO JSPLKZUTYZBBKA-UHFFFAOYSA-N 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- BFDBKMOZYNOTPK-UHFFFAOYSA-N vonoprazan Chemical compound C=1C=CN=CC=1S(=O)(=O)N1C=C(CNC)C=C1C1=CC=CC=C1F BFDBKMOZYNOTPK-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
- C07D211/94—Oxygen atom, e.g. piperidine N-oxide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- 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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- 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
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0455—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/16—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom containing only one pyridine ring
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Optics & Photonics (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Neurology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Claims (5)
- Szí i rí Ip i ri di π -s zárm azékok és azok alkalmazása amüoid piakkok megkötésére és leképezésére Szabadalmi igénypontok 1. Λképletü vegyület.
- 2. Az 1. igénypont szerinti vegyület et tartalmazó gyógyászati készítmény.
- 3. Diagnosztikai készítmény amikkel lerakódások leképezésére, mely egy k igénypont szerinti radioaktívon jelölt vegyüíetet tartalmaz.
- 4. A 3. igénypont szerinti diagnosztikai készítmény amüoid lerakódások leképezésében törté-no alkalmazásra* melynek sorén: a, egy emlősbe a diagnosztikai készítmény detektálható mennyiségét visszük be; b, megfelelő időt biztosítunk a jelölt vegyűletnek az amiloíd lerakódásokkal történő kapcsolódására: és e. meghatározzuk az egy vagy több amüoid lerakodással kapcsolódott jelölt vegyüíetet.
- 5. Λ '2. igénypont szerinti készítmény emlősben amiloid plakk aggregáció gátlásában történő alkalmazásra.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US78715606P | 2006-03-30 | 2006-03-30 |
Publications (1)
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| HUE032660T2 true HUE032660T2 (hu) | 2017-10-30 |
Family
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| HUE11152124A HUE032660T2 (hu) | 2006-03-30 | 2007-03-26 | Sztirilpiridin-származékok és azok alkalmazása amiloid plakkok megkötésére és leképezésére |
| HUS1300028C HUS1300028I1 (hu) | 2006-03-30 | 2013-06-27 | Sztiril-piridin-származékok és alkalmazásuk amyloid-plakkok megkötésére és leképezésére |
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| HUS1300028C HUS1300028I1 (hu) | 2006-03-30 | 2013-06-27 | Sztiril-piridin-származékok és alkalmazásuk amyloid-plakkok megkötésére és leképezésére |
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| EP (3) | EP1999109B1 (hu) |
| JP (1) | JP5290954B2 (hu) |
| KR (1) | KR101376807B1 (hu) |
| CN (1) | CN101522624B (hu) |
| AT (1) | ATE539060T1 (hu) |
| AU (1) | AU2007243712B2 (hu) |
| BR (1) | BRPI0710225B1 (hu) |
| CA (1) | CA2644530C (hu) |
| CR (1) | CR10329A (hu) |
| CY (3) | CY1113048T1 (hu) |
| DK (2) | DK1999109T3 (hu) |
| EA (1) | EA017898B1 (hu) |
| EC (1) | ECSP088783A (hu) |
| ES (2) | ES2628882T3 (hu) |
| FR (1) | FR13C0034I2 (hu) |
| GT (1) | GT200800201A (hu) |
| HR (2) | HRP20120135T1 (hu) |
| HU (2) | HUE032660T2 (hu) |
| IL (1) | IL193567A (hu) |
| LT (1) | LT2363392T (hu) |
| LU (1) | LU92232I2 (hu) |
| MX (1) | MX2008012527A (hu) |
| NO (2) | NO342090B1 (hu) |
| NZ (1) | NZ570887A (hu) |
| PL (2) | PL1999109T3 (hu) |
| PT (2) | PT1999109E (hu) |
| RS (2) | RS56171B1 (hu) |
| SG (1) | SG173338A1 (hu) |
| SI (2) | SI1999109T1 (hu) |
| TW (1) | TWI399366B (hu) |
| UA (1) | UA97802C2 (hu) |
| WO (1) | WO2007126733A2 (hu) |
| ZA (1) | ZA200807955B (hu) |
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| EP1999109B1 (en) * | 2006-03-30 | 2011-12-28 | The Trustees Of The University Of Pennsylvania | Styrylpyridine derivatives and their use for binding and imaging amyloid plaques |
| EP2172444A4 (en) * | 2007-07-04 | 2010-12-22 | Univ Tohoku | PET SENSOR HAVING ALCOXY GROUP SUBSTITUTED BY FLUORIN ATOM AND HYDROXY GROUP |
| 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 |
| WO2010078370A1 (en) * | 2008-12-31 | 2010-07-08 | Avid Radiopharmaceuticals, Inc. | Synthesis of 18f-radiolabeled styrylpyridines from tosylate precursors and stable pharmaceutical compositions thereof |
| EP2451760A1 (en) * | 2009-07-10 | 2012-05-16 | Bayer Pharma Aktiengesellschaft | Usage of low to medium-pressure liquid chromatography for the purification of radiotracers |
| US20120263646A1 (en) | 2009-10-15 | 2012-10-18 | Guerbet | Imaging agents and their use for the diagnostic in vivo of neurodegenerative diseases, notably alzheimer's disease and derivative diseases |
| AU2010334929B2 (en) * | 2009-12-23 | 2015-04-23 | Life Molecular Imaging Limited | Formulations suitable for pet imaging with hydrophobic pet agents |
| WO2011141515A1 (en) | 2010-05-14 | 2011-11-17 | Bayer Pharma Aktiengesellschaft | Diagnostic agents for amyloid beta imaging |
| AU2011260421B2 (en) | 2010-06-04 | 2015-06-04 | Life Molecular Imaging Limited | Method for production of F-18 labeled amyloid beta ligands |
| 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 |
| MX2012014116A (es) * | 2010-06-04 | 2013-08-08 | Piramal Imaging Sa | Metodo para la produccion de ligandos beta amiloide marcados con 18f. |
| EA025823B1 (ru) * | 2010-06-04 | 2017-02-28 | Пирамаль Имэджинг Са | Способ получения f-18 меченых лигандов бета-амилоида |
| CN101891674B (zh) * | 2010-06-24 | 2012-11-14 | 山东大学 | 4-苯乙烯基吡啶类化合物及其制备方法与应用 |
| US9259495B2 (en) * | 2010-10-12 | 2016-02-16 | Mayo Foundation For Medical Education And Research | Imaging of meningiomas using phenylbenzothiazole, stilbene, or biphenylalkyne derivatives |
| US20140079635A1 (en) * | 2011-03-30 | 2014-03-20 | Case Western Reserve University | Molecular probes for detecting lipid composition |
| WO2012145169A2 (en) | 2011-04-21 | 2012-10-26 | The Regents Of The University Of California | Functionalized magnetic nanoparticles and use in imaging amyloid deposits and neurofibrillary tangles |
| EP2768790A1 (en) | 2011-10-19 | 2014-08-27 | Piramal Imaging SA | IMPROVED METHOD FOR PRODUCTION OF F-18 LABELED Aß LIGANDS |
| CN104244991A (zh) | 2012-04-10 | 2014-12-24 | 蓝瑟斯医学影像公司 | 放射性药物合成方法 |
| JP6099045B2 (ja) * | 2013-04-30 | 2017-03-22 | 国立大学法人京都大学 | トリアゾロピリミジン誘導体化合物 |
| 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 |
| CN103645254B (zh) * | 2013-11-28 | 2015-01-07 | 江苏省原子医学研究所 | 一种Aβ斑块显像剂前体AV45的含量分析方法 |
| SG11201609281UA (en) * | 2014-05-13 | 2016-12-29 | Hoffmann La Roche | Deuterated heterocyclic compounds and their use as imaging agents |
| AU2016308189B2 (en) * | 2015-08-18 | 2021-03-11 | The Regents Of The University Of California | Nitroxide containing amyloid binding agents for imaging and therapeutic uses |
| US10300155B2 (en) | 2015-12-31 | 2019-05-28 | Washington University | Alpha-synuclein ligands |
| CN109400615B (zh) * | 2017-08-18 | 2021-07-16 | 上海交通大学医学院附属新华医院 | 一种靶向β-淀粉样蛋白的香豆素类化合物及其制备与应用 |
| CN108299287A (zh) * | 2018-01-02 | 2018-07-20 | 北京师范大学 | 与Aβ斑块具有高亲和力的N2S2类吡啶基苯乙烯化合物 |
| CN114805190A (zh) * | 2022-06-08 | 2022-07-29 | 吉林大学第一医院 | 一种甲基苯胺类Aβ蛋白显像剂的双柱合成方法 |
| WO2024107620A1 (en) | 2022-11-14 | 2024-05-23 | Eli Lilly And Company | Polymorphic forms of florbetapir precursor av-105 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992000963A1 (en) * | 1990-07-12 | 1992-01-23 | Yoshitomi Pharmaceutical Industries, Ltd. | Styryl compounds and use thereof as medicine |
| JPH0545875A (ja) * | 1991-08-08 | 1993-02-26 | Konica Corp | 感光性組成物 |
| US6020436A (en) * | 1993-03-09 | 2000-02-01 | The Chromaline Corporation | Photosensitive resin composition |
| TW544448B (en) * | 1997-07-11 | 2003-08-01 | Novartis Ag | Pyridine derivatives |
| WO2001070667A1 (fr) * | 2000-03-22 | 2001-09-27 | Bf Research Institute, Inc. | Sonde de diagnostic par image, a base d'azobenzene substitue ou d'un analogue de celui-ci, pour les maladies imputables a l'accumulation d'amyloide et composition pour le diagnostic par image le contenant |
| US8007954B2 (en) | 2000-11-09 | 2011-08-30 | The Trustees Of The University Of Pennsylvania | Use of sulfur-containing fuels for direct oxidation fuel cells |
| JP2002182254A (ja) | 2000-12-18 | 2002-06-26 | Fuji Photo Film Co Ltd | 非線形光学材料とその製造方法 |
| US7250525B2 (en) * | 2001-08-27 | 2007-07-31 | The Trustees Of The University Of Pennsylvania | Stilbene derivatives and their use for binding and imaging amyloid plaques |
| CA2488273A1 (en) | 2002-06-06 | 2003-12-18 | The Trustees Of The University Of Pennsylvania | Ceramic anodes and method of producing the same |
| AU2003258612A1 (en) * | 2002-08-14 | 2004-03-03 | 4Sc Ag | Pyrimidones as antiviral agents |
| JP4482352B2 (ja) | 2004-03-11 | 2010-06-16 | 本田技研工業株式会社 | 固体高分子型燃料電池 |
| WO2006078384A2 (en) * | 2004-12-17 | 2006-07-27 | The Trustees Of The University Of Pennsylvania | Stilbene derivatives and their use |
| SG194363A1 (en) * | 2004-12-17 | 2013-11-29 | Univ Pennsylvania | Stilbene derivatives and their use for binding and imaging amyloid plaques |
| CA2617319A1 (en) | 2005-06-24 | 2007-01-04 | The Trustees Of The University Of Pennsylvania | Radiolabeled-pegylation of ligands for use as imaging agents |
| EP1999109B1 (en) | 2006-03-30 | 2011-12-28 | The Trustees Of The University Of Pennsylvania | Styrylpyridine derivatives and their use for binding and imaging amyloid plaques |
| US20080253967A1 (en) * | 2007-04-13 | 2008-10-16 | Kung Hank F | Halo-Stilbene Derivatives And Their Use For Binding And Imaging Of Amyloid Plaques |
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