JP5347164B2 - ニトロ−イミダゾール低酸素造影剤 - Google Patents
ニトロ−イミダゾール低酸素造影剤 Download PDFInfo
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- JP5347164B2 JP5347164B2 JP2010502341A JP2010502341A JP5347164B2 JP 5347164 B2 JP5347164 B2 JP 5347164B2 JP 2010502341 A JP2010502341 A JP 2010502341A JP 2010502341 A JP2010502341 A JP 2010502341A JP 5347164 B2 JP5347164 B2 JP 5347164B2
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- Prior art keywords
- alkyl
- compound
- group
- alkylenyl
- formula
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- 206010021143 Hypoxia Diseases 0.000 title claims abstract description 49
- 230000007954 hypoxia Effects 0.000 title claims description 14
- YZEUHQHUFTYLPH-UHFFFAOYSA-N 2-nitroimidazole Chemical compound [O-][N+](=O)C1=NC=CN1 YZEUHQHUFTYLPH-UHFFFAOYSA-N 0.000 title abstract description 9
- 239000002872 contrast media Substances 0.000 title description 7
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 65
- 230000001146 hypoxic effect Effects 0.000 claims abstract description 35
- 230000000302 ischemic effect Effects 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 68
- 150000001875 compounds Chemical class 0.000 claims description 65
- 125000005466 alkylenyl group Chemical group 0.000 claims description 56
- 210000004027 cell Anatomy 0.000 claims description 37
- 239000000203 mixture Substances 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 30
- 201000011510 cancer Diseases 0.000 claims description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 24
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 150000003573 thiols Chemical class 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 238000000163 radioactive labelling Methods 0.000 claims description 13
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 11
- 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 claims description 9
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- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 238000001514 detection method Methods 0.000 claims description 8
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 8
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- 150000001540 azides Chemical group 0.000 claims description 4
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- 125000001425 triazolyl group Chemical group 0.000 claims description 3
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 2
- 150000004957 nitroimidazoles Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims 1
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- 230000002708 enhancing effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 88
- 238000006243 chemical reaction Methods 0.000 description 52
- KRHYYFGTRYWZRS-BJUDXGSMSA-N ac1l2y5h Chemical group [18FH] KRHYYFGTRYWZRS-BJUDXGSMSA-N 0.000 description 50
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- 239000000243 solution Substances 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 29
- 239000000741 silica gel Substances 0.000 description 26
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- 239000003480 eluent Substances 0.000 description 24
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 19
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- 239000007787 solid Substances 0.000 description 17
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 16
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 16
- 229940125904 compound 1 Drugs 0.000 description 16
- 239000000463 material Substances 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 12
- 125000003118 aryl group Chemical group 0.000 description 12
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- 125000000753 cycloalkyl group Chemical group 0.000 description 11
- 125000005843 halogen group Chemical group 0.000 description 11
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- 125000001072 heteroaryl group Chemical group 0.000 description 10
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- 239000002904 solvent Substances 0.000 description 9
- 241000700159 Rattus Species 0.000 description 8
- 125000003545 alkoxy group Chemical group 0.000 description 8
- 125000004001 thioalkyl group Chemical group 0.000 description 8
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 238000012879 PET imaging Methods 0.000 description 7
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- 125000000592 heterocycloalkyl group Chemical group 0.000 description 7
- 125000005647 linker group Chemical group 0.000 description 7
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- 238000001953 recrystallisation Methods 0.000 description 7
- ZSSPATINHRVRTN-UHFFFAOYSA-N 3-fluoro-2-[4-[(2-nitroimidazol-1-yl)methyl]triazol-1-yl]propan-1-ol Chemical compound N1=NN(C(CF)CO)C=C1CN1C([N+]([O-])=O)=NC=C1 ZSSPATINHRVRTN-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- 150000001345 alkine derivatives Chemical class 0.000 description 6
- 235000010323 ascorbic acid Nutrition 0.000 description 6
- 239000011668 ascorbic acid Substances 0.000 description 6
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- 229910052760 oxygen Inorganic materials 0.000 description 6
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- RMFRVPCPYRNDJE-UHFFFAOYSA-N 1-fluoro-3-[4-[(2-nitroimidazol-1-yl)methyl]triazol-1-yl]propan-2-ol Chemical compound N1=NN(CC(CF)O)C=C1CN1C([N+]([O-])=O)=NC=C1 RMFRVPCPYRNDJE-UHFFFAOYSA-N 0.000 description 5
- APOYTRAZFJURPB-UHFFFAOYSA-N 2-methoxy-n-(2-methoxyethyl)-n-(trifluoro-$l^{4}-sulfanyl)ethanamine Chemical compound COCCN(S(F)(F)F)CCOC APOYTRAZFJURPB-UHFFFAOYSA-N 0.000 description 5
- SPXOTSHWBDUUMT-UHFFFAOYSA-M 4-nitrobenzenesulfonate Chemical compound [O-][N+](=O)C1=CC=C(S([O-])(=O)=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-M 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
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- 239000002243 precursor Substances 0.000 description 5
- 238000011894 semi-preparative HPLC Methods 0.000 description 5
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 5
- 235000010378 sodium ascorbate Nutrition 0.000 description 5
- 229960005055 sodium ascorbate Drugs 0.000 description 5
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 5
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- GSOZMIFQWCNBHZ-UHFFFAOYSA-N (3-azido-2-hydroxypropyl) 4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(=O)(=O)OCC(O)CN=[N+]=[N-])C=C1 GSOZMIFQWCNBHZ-UHFFFAOYSA-N 0.000 description 4
- AGCPPSNKHQEFRX-UHFFFAOYSA-N 1-azidoethanol Chemical compound CC(O)N=[N+]=[N-] AGCPPSNKHQEFRX-UHFFFAOYSA-N 0.000 description 4
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- FSKJVNDEVKJKAS-UHFFFAOYSA-N 2-azidopropane-1,3-diol Chemical compound OCC(CO)N=[N+]=[N-] FSKJVNDEVKJKAS-UHFFFAOYSA-N 0.000 description 4
- UVQPFNDBXKEGFH-UHFFFAOYSA-N 2-nitro-1-prop-1-ynylimidazole Chemical compound CC#CN1C=CN=C1[N+]([O-])=O UVQPFNDBXKEGFH-UHFFFAOYSA-N 0.000 description 4
- PVVVCERWZQLGGT-UHFFFAOYSA-N 4-(azidomethyl)-2,2-dimethyl-1,3-dioxolane Chemical compound CC1(C)OCC(CN=[N+]=[N-])O1 PVVVCERWZQLGGT-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
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- HOKUHBQGCWLJBK-UHFFFAOYSA-N [3-hydroxy-2-[4-[(2-nitroimidazol-1-yl)methyl]triazol-1-yl]propyl] acetate Chemical compound N1=NN(C(CO)COC(=O)C)C=C1CN1C([N+]([O-])=O)=NC=C1 HOKUHBQGCWLJBK-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4192—1,2,3-Triazoles
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/002—Heterocyclic compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
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| US92193207P | 2007-04-05 | 2007-04-05 | |
| US60/921,932 | 2007-04-05 | ||
| US96425407P | 2007-08-10 | 2007-08-10 | |
| US60/964,254 | 2007-08-10 | ||
| PCT/US2008/059505 WO2008124651A2 (en) | 2007-04-05 | 2008-04-04 | Nitro-imidazole hypoxia imaging agents |
Publications (3)
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| JP2010523596A JP2010523596A (ja) | 2010-07-15 |
| JP2010523596A5 JP2010523596A5 (enExample) | 2011-05-12 |
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| EP (1) | EP2132200B1 (enExample) |
| JP (1) | JP5347164B2 (enExample) |
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| CN (1) | CN101652360B (enExample) |
| CA (1) | CA2683433C (enExample) |
| WO (1) | WO2008124651A2 (enExample) |
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| CN101652360B (zh) * | 2007-04-05 | 2014-06-25 | 美国西门子医疗解决公司 | 硝基咪唑低氧造影剂 |
| CN101709060B (zh) * | 2009-12-02 | 2013-05-01 | 北京师范大学 | 一种f-三唑环-聚乙二醇-甲硝唑化合物及其制备方法 |
| CN102858752B (zh) | 2010-02-08 | 2018-10-16 | 兰休斯医疗成像公司 | 用于合成显像剂和其中间体的方法和装置 |
| EP2556372A1 (en) | 2010-04-08 | 2013-02-13 | Siemens Medical Solutions USA, Inc. | Synthesis of 18f-labeled tracers in hydrous organic solvents |
| US10639608B2 (en) | 2010-04-08 | 2020-05-05 | Siemens Medical Solutions Usa, Inc. | System, device and method for preparing tracers and transferring materials during radiosynthesis |
| CN101921263A (zh) * | 2010-04-16 | 2010-12-22 | 兰州大学 | 2-硝基咪唑衍生物及其用途和制备方法 |
| RU2710736C2 (ru) | 2010-05-11 | 2020-01-10 | Лантеус Медикал Имэджинг, Инк. | Композиции, способы и системы для синтеза и применение визуализирующих средств |
| KR102527562B1 (ko) | 2011-09-09 | 2023-05-03 | 랜티우스 메디컬 이메징, 인크. | 영상화제의 합성 및 사용을 위한 조성물, 방법 및 시스템 |
| US9061143B2 (en) | 2011-10-14 | 2015-06-23 | Sumitomo Heavy Industries, Ltd. | Charged particle beam irradiation system and charged particle beam irradiation planning method |
| WO2014007650A1 (en) * | 2011-12-23 | 2014-01-09 | Auckland Uniservices Limited | Compounds and methods for selective imaging and/or ablation |
| WO2014062856A1 (en) | 2012-10-16 | 2014-04-24 | Halozyme, Inc. | Hypoxia and hyaluronan and markers thereof for diagnosis and monitoring of diseases and conditions and related methods |
| WO2015104589A1 (en) | 2014-01-13 | 2015-07-16 | Shanghai Lawring Biomedical Co., Ltd | Dendrimer compositions, methods of synthesis, and uses thereof |
| WO2016047424A1 (ja) * | 2014-09-25 | 2016-03-31 | 日本メジフィジックス株式会社 | 腎イメージング剤 |
| WO2016179117A1 (en) * | 2015-05-01 | 2016-11-10 | Vanderbilt University | Composition and method for detecting hypoxia |
| US10695450B2 (en) | 2016-07-26 | 2020-06-30 | Laboratoires Cyclopharma | Synthesis of a radioactive agent composition |
| CN106977501A (zh) * | 2017-03-20 | 2017-07-25 | 华东师范大学 | 一种基于2‑硝基咪唑‑1‑烷基醇的低氧激活前药 |
| FR3068695B1 (fr) * | 2017-07-05 | 2019-08-16 | Centre National De La Recherche Scientifique | Composes utiles comme agent d'imagerie de l'hypoxie |
| CA3076256A1 (en) * | 2017-09-19 | 2019-03-28 | The Governors Of The University Of Alberta | Markers, conjugates, compositions and methods for hypoxia imaging, mapping, and therapy |
| US20200276338A1 (en) * | 2017-09-19 | 2020-09-03 | The Governors Of The University Of Alberta | Bioreductively-activated compounds, their prodrugs, radiopharmaceuticals, the compositions, and their applications in multimodal theranostic management of hypoxia diseases including cancer |
| WO2021138540A1 (en) | 2020-01-03 | 2021-07-08 | Berg Llc | Polycyclic amides as ube2k modulators for treating cancer |
| CN111233821B (zh) * | 2020-01-20 | 2022-12-27 | 上海交通大学医学院附属仁济医院 | 含3-羟基苯甲酸基团的新抗霉素衍生物及其制备方法和应用 |
| CN114478489B (zh) * | 2022-01-18 | 2023-04-28 | 中国科学院精密测量科学与技术创新研究院 | 一种氟-19修饰的硝基咪唑化合物及其衍生物的制备方法和应用 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US5674693A (en) * | 1994-03-18 | 1997-10-07 | Natural Pharmacia International Inc. | Derivatives of 2-nitro-imidazoles as hypoxic cell markers |
| US5721265A (en) * | 1994-08-05 | 1998-02-24 | Sri International | Fluorinated 2-nitroimidazole analogs for detecting hypoxic tumor cells |
| DE60022058T2 (de) * | 1999-08-11 | 2006-06-01 | Universite Catholique De Louvain | Verfahren zur herstellung von [18f] radiomarkierten nitroimidazol-derivaten zum nachweis zellulärer hypoxie |
| CN101652360B (zh) * | 2007-04-05 | 2014-06-25 | 美国西门子医疗解决公司 | 硝基咪唑低氧造影剂 |
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2008
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- 2008-04-04 US US12/098,390 patent/US7807394B2/en not_active Expired - Fee Related
- 2008-04-04 JP JP2010502341A patent/JP5347164B2/ja not_active Expired - Fee Related
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- 2008-04-04 KR KR1020097023183A patent/KR101523257B1/ko not_active Expired - Fee Related
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Also Published As
| Publication number | Publication date |
|---|---|
| KR20090130106A (ko) | 2009-12-17 |
| CN101652360A (zh) | 2010-02-17 |
| CN101652360B (zh) | 2014-06-25 |
| CA2683433C (en) | 2016-10-11 |
| US20090010846A1 (en) | 2009-01-08 |
| US7977361B2 (en) | 2011-07-12 |
| KR101523257B1 (ko) | 2015-05-27 |
| EP2132200B1 (en) | 2016-03-23 |
| WO2008124651A2 (en) | 2008-10-16 |
| CA2683433A1 (en) | 2008-10-16 |
| JP2010523596A (ja) | 2010-07-15 |
| EP2132200A2 (en) | 2009-12-16 |
| WO2008124651A3 (en) | 2009-04-02 |
| US7807394B2 (en) | 2010-10-05 |
| US20110002850A1 (en) | 2011-01-06 |
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