AU2015308769A1 - Probes for imaging huntingtin protein - Google Patents
Probes for imaging huntingtin protein Download PDFInfo
- Publication number
- AU2015308769A1 AU2015308769A1 AU2015308769A AU2015308769A AU2015308769A1 AU 2015308769 A1 AU2015308769 A1 AU 2015308769A1 AU 2015308769 A AU2015308769 A AU 2015308769A AU 2015308769 A AU2015308769 A AU 2015308769A AU 2015308769 A1 AU2015308769 A1 AU 2015308769A1
- Authority
- AU
- Australia
- Prior art keywords
- imidazo
- pyridine
- methoxy
- carbonitrile
- methylamino
- 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.)
- Abandoned
Links
- 238000003384 imaging method Methods 0.000 title claims description 13
- 108050004784 Huntingtin Proteins 0.000 title claims description 8
- 102000016252 Huntingtin Human genes 0.000 title claims description 6
- 239000000523 sample Substances 0.000 title description 3
- 238000000034 method Methods 0.000 claims abstract description 172
- 150000001875 compounds Chemical class 0.000 claims abstract description 76
- 239000012216 imaging agent Substances 0.000 claims abstract description 59
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- -1 bromo, fluoro, methoxy, hydroxyl Chemical group 0.000 claims description 126
- 125000000217 alkyl group Chemical group 0.000 claims description 120
- 125000001072 heteroaryl group Chemical group 0.000 claims description 74
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 52
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 47
- 125000003545 alkoxy group Chemical group 0.000 claims description 43
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 claims description 39
- 108090000623 proteins and genes Proteins 0.000 claims description 32
- 102000004169 proteins and genes Human genes 0.000 claims description 32
- 238000002600 positron emission tomography Methods 0.000 claims description 28
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 27
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 125000004432 carbon atom Chemical group C* 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 208000023105 Huntington disease Diseases 0.000 claims description 17
- 210000004556 brain Anatomy 0.000 claims description 17
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 16
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims description 15
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- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 208000037273 Pathologic Processes Diseases 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 230000009054 pathological process Effects 0.000 claims description 12
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Chemical group C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 11
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 11
- 238000002595 magnetic resonance imaging Methods 0.000 claims description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 10
- 238000012879 PET imaging Methods 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- KIYOXVPZRXLLDR-UHFFFAOYSA-N imidazo[1,2-a]pyridine-7-carbonitrile Chemical compound C1=C(C#N)C=CN2C=CN=C21 KIYOXVPZRXLLDR-UHFFFAOYSA-N 0.000 claims description 9
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- VJFJMCSJLDRDRR-UHFFFAOYSA-N 2-[5-[(5-methoxypyrazin-2-yl)methoxy]pyridin-2-yl]-3-(methylamino)imidazo[1,2-a]pyridine-7-carbonitrile Chemical compound COC=1N=CC(=NC=1)COC=1C=CC(=NC=1)C=1N=C2N(C=CC(=C2)C#N)C=1NC VJFJMCSJLDRDRR-UHFFFAOYSA-N 0.000 claims description 3
- XAWNDICSNACTDK-UHFFFAOYSA-N 3-(methylamino)-2-[3-(pyridin-3-ylmethoxymethyl)phenyl]imidazo[1,2-a]pyridine-7-carbonitrile Chemical compound CNC1=C(N=C2N1C=CC(=C2)C#N)C1=CC(=CC=C1)COCC=1C=NC=CC=1 XAWNDICSNACTDK-UHFFFAOYSA-N 0.000 claims description 3
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- DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 3
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
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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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- A61K51/0453—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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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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- 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
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0459—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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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
- A61K51/0497—Organic compounds conjugates with a carrier being an organic compounds
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- 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
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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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- Public Health (AREA)
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- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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| US20190381030A1 (en) * | 2017-10-12 | 2019-12-19 | University Of Kansas | Methods of treating radiation induced gastrointestinal syndrome (rigs) and related disease states using yel002/bcn057 |
| US11389438B2 (en) | 2019-02-25 | 2022-07-19 | Chdi Foundation, Inc. | Compounds for targeting mutant huntingtin protein and uses thereof |
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| BRPI0806621A2 (pt) | 2007-01-22 | 2011-09-13 | Astrazeneca Ab | composto, uso de um composto, composição farmacêutica, e, método in vivo para medir depósitos amilóides em um indivìduo |
| KR20100101576A (ko) * | 2007-10-30 | 2010-09-17 | 니혼 메디피직스 가부시키가이샤 | 신규 아밀로이드 친화성 화합물의 사용 및 제조 방법 |
| FR2928923B1 (fr) * | 2008-03-21 | 2010-04-23 | Sanofi Aventis | Derives polysubstitues de 2-heteroaryl-6-phenyl-imidazo °1,2-a!pyridines, leur preparation et leur application en therapeutiques |
| EP2323697A2 (en) * | 2008-07-24 | 2011-05-25 | Siemens Medical Solutions USA, Inc. | Imaging agents useful for identifying ad pathology |
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| TWI528977B (zh) * | 2011-05-20 | 2016-04-11 | Nihon Mediphysics Co Ltd | New amyloid affinity products |
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| RU2671506C2 (ru) * | 2013-09-26 | 2018-11-01 | Ф. Хоффманн-Ля Рош Аг | Имидазо[1,2-а]пиридин-7-амины в качестве средств визуализации |
| EP3190888B1 (en) | 2014-08-29 | 2020-06-10 | CHDI Foundation, Inc. | Probes for imaging huntingtin protein |
| EA037275B1 (ru) | 2014-08-29 | 2021-03-03 | Сиэйчдиай Фаундэйшн, Инк. | Зонды для визуализации белка хантингтина |
| WO2016033440A1 (en) | 2014-08-29 | 2016-03-03 | Chdi Foundation, Inc. | Probes for imaging huntingtin protein |
| EA035646B1 (ru) | 2014-08-29 | 2020-07-21 | Сиэйчдиай Фаундэйшн, Инк. | Зонды для визуализации белка хантингтина |
| CN108135172B (zh) | 2015-08-28 | 2021-03-30 | Chdi基金会股份有限公司 | 用于成像亨廷顿蛋白的探针 |
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