TWI513698B - 做為ｔａｕ－ｐｅｔ－配位體之二氮雜咔唑衍生物 - Google Patents
做為ｔａｕ－ｐｅｔ－配位體之二氮雜咔唑衍生物 Download PDFInfo
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- TWI513698B TWI513698B TW103134795A TW103134795A TWI513698B TW I513698 B TWI513698 B TW I513698B TW 103134795 A TW103134795 A TW 103134795A TW 103134795 A TW103134795 A TW 103134795A TW I513698 B TWI513698 B TW I513698B
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- pharmaceutically acceptable
- addition salt
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- 239000003446 ligand Substances 0.000 title description 2
- BZHCVCNZIJZMRN-UHFFFAOYSA-N 9h-pyridazino[3,4-b]indole Chemical class N1=CC=C2C3=CC=CC=C3NC2=N1 BZHCVCNZIJZMRN-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 93
- 102000013498 tau Proteins Human genes 0.000 claims description 43
- 108010026424 tau Proteins Proteins 0.000 claims description 43
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 36
- 239000002253 acid Substances 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 20
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- 208000024827 Alzheimer disease Diseases 0.000 claims description 17
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- 238000000034 method Methods 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 15
- 238000003384 imaging method Methods 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
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- 230000027455 binding Effects 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 8
- FDMOHTOITMTGNG-UHFFFAOYSA-N 11-(6-fluoropyridin-3-yl)-4,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaene Chemical compound Fc1ccc(cn1)-c1ccc2c(n1)[nH]c1ccncc21 FDMOHTOITMTGNG-UHFFFAOYSA-N 0.000 claims description 7
- 241000124008 Mammalia Species 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 229910052734 helium Inorganic materials 0.000 claims description 6
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims description 6
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- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 claims description 6
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- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical group [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 4
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- DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 claims description 3
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 201000011240 Frontotemporal dementia Diseases 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
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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
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- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- 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
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
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- A—HUMAN NECESSITIES
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- 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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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- 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
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- 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
- C07D471/14—Ortho-condensed systems
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- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
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- G—PHYSICS
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- Psychiatry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13187764 | 2013-10-08 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201520212A TW201520212A (zh) | 2015-06-01 |
| TWI513698B true TWI513698B (zh) | 2015-12-21 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| TW103134795A TWI513698B (zh) | 2013-10-08 | 2014-10-06 | 做為ｔａｕ－ｐｅｔ－配位體之二氮雜咔唑衍生物 |
Country Status (32)
| Country | Link |
|---|---|
| US (2) | US10004817B2 (OSRAM) |
| EP (1) | EP3055308B1 (OSRAM) |
| JP (1) | JP6194416B2 (OSRAM) |
| KR (1) | KR101770531B1 (OSRAM) |
| CN (1) | CN105358558B (OSRAM) |
| AR (1) | AR097931A1 (OSRAM) |
| AU (1) | AU2014333996B2 (OSRAM) |
| CA (1) | CA2917191C (OSRAM) |
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| TWI808119B (zh) * | 2018-01-24 | 2023-07-11 | 英商生命分子影像有限公司 | 用於pet顯像之診斷組合物、一種用於製造該診斷組合物之方法及其於診斷中之用途 |
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| LT2247558T (lt) | 2008-02-14 | 2022-04-11 | Eli Lilly And Company | Nauji vizualizavimo agentai neurologinės disfunkcijos aptikimui |
| NO3055308T3 (OSRAM) | 2013-10-08 | 2018-04-21 | ||
| SI3143011T1 (sl) | 2014-05-13 | 2021-08-31 | F. Hoffmann-La Roche Ag | Devterirane heterociklične spojine in njihova uporaba kot kontrastna sredstva |
| CA2973648C (en) | 2015-02-02 | 2023-09-26 | Ucb Biopharma Sprl | 9h-pyrrolo-dipyridine derivatives |
| EP3118202A1 (en) | 2015-07-15 | 2017-01-18 | AC Immune S.A. | Dihydropyridopyrrole derivatives as tau-pet-ligands |
| EP3322707A1 (en) | 2015-07-15 | 2018-05-23 | AC Immune SA | Novel imaging compounds |
| JP7059270B2 (ja) * | 2016-07-22 | 2022-04-25 | エーシー・イミューン・エス・アー | タウタンパク質凝集体を画像化するための化合物 |
| IL264239B (en) * | 2016-07-22 | 2022-08-01 | Ac Immune Sa | Compounds for imaging tau protein aggregates |
| WO2018024642A1 (en) | 2016-08-02 | 2018-02-08 | Ucb Biopharma Sprl | 9h-pyrrolo-dipyridine derivatives |
| WO2018024643A1 (en) | 2016-08-02 | 2018-02-08 | Ucb Biopharma Sprl | 9h-pyrrolo-dipyridine derivatives |
| CN109689653B (zh) * | 2016-09-09 | 2022-04-12 | 豪夫迈·罗氏有限公司 | 用于制备2-(6-硝基吡啶-3-基)-9H-二吡啶并[2，3-b；3’，4’-d]吡咯的方法 |
| US20210038747A1 (en) * | 2018-01-24 | 2021-02-11 | Ac Immune Sa | Novel method of preparing an imaging compound |
| EP3743423A1 (en) | 2018-01-24 | 2020-12-02 | AC Immune SA | Gamma-carboline compounds for the detection of tau aggregates |
| EP3743426A1 (en) | 2018-01-24 | 2020-12-02 | AC Immune SA | Azacarboline compounds for the detection of tau aggregates |
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| US20110124654A1 (en) | 2008-06-11 | 2011-05-26 | Huifen Chen | Diazacarbazoles and methods of use |
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| US20150368244A1 (en) * | 2011-01-31 | 2015-12-24 | Genentech, Inc. | Diazacarbazoles and methods of use |
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