ES2281927T3 - Complejantes tetraaza- o n2s2-, y su uso en radiodiagnostico o en radioterapia. - Google Patents
Complejantes tetraaza- o n2s2-, y su uso en radiodiagnostico o en radioterapia. Download PDFInfo
- Publication number
- ES2281927T3 ES2281927T3 ES98912032T ES98912032T ES2281927T3 ES 2281927 T3 ES2281927 T3 ES 2281927T3 ES 98912032 T ES98912032 T ES 98912032T ES 98912032 T ES98912032 T ES 98912032T ES 2281927 T3 ES2281927 T3 ES 2281927T3
- Authority
- ES
- Spain
- Prior art keywords
- hydrogen
- independently selected
- less
- nitrogen
- acid
- 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.)
- Expired - Lifetime
Links
- 238000001959 radiotherapy Methods 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 165
- 239000001257 hydrogen Substances 0.000 claims abstract description 97
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 97
- 229910052751 metal Inorganic materials 0.000 claims abstract description 67
- 239000002184 metal Substances 0.000 claims abstract description 67
- 125000003118 aryl group Chemical group 0.000 claims abstract description 32
- 125000004429 atom Chemical group 0.000 claims abstract description 29
- 238000000034 method Methods 0.000 claims abstract description 29
- 238000004519 manufacturing process Methods 0.000 claims abstract description 14
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 14
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 209
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 174
- -1 indian Chemical compound 0.000 claims description 75
- 239000002253 acid Substances 0.000 claims description 68
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- 229910052717 sulfur Inorganic materials 0.000 claims description 48
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 47
- 150000002431 hydrogen Chemical class 0.000 claims description 47
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 47
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 46
- 239000011593 sulfur Substances 0.000 claims description 42
- 230000021615 conjugation Effects 0.000 claims description 41
- 229910052736 halogen Inorganic materials 0.000 claims description 38
- 150000002367 halogens Chemical class 0.000 claims description 38
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 37
- 125000003545 alkoxy group Chemical group 0.000 claims description 35
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 35
- 229910052799 carbon Inorganic materials 0.000 claims description 33
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 30
- 239000013522 chelant Substances 0.000 claims description 29
- 229910052727 yttrium Inorganic materials 0.000 claims description 26
- 150000002148 esters Chemical class 0.000 claims description 22
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 18
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 239000001301 oxygen Substances 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- ABLZXFCXXLZCGV-UHFFFAOYSA-N phosphonic acid group Chemical group P(O)(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 12
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- 239000012634 fragment Substances 0.000 claims description 8
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- WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 claims description 7
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- 229910052763 palladium Inorganic materials 0.000 claims description 6
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- 239000010948 rhodium Substances 0.000 claims description 5
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- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 3
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052737 gold Inorganic materials 0.000 claims description 3
- KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 claims description 3
- 229910052703 rhodium Inorganic materials 0.000 claims description 3
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 3
- 125000006413 ring segment Chemical group 0.000 claims description 3
- 229910052707 ruthenium Inorganic materials 0.000 claims description 3
- 229910052688 Gadolinium Inorganic materials 0.000 claims description 2
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- 229940079593 drug Drugs 0.000 claims description 2
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 claims description 2
- OHSVLFRHMCKCQY-UHFFFAOYSA-N lutetium atom Chemical compound [Lu] OHSVLFRHMCKCQY-UHFFFAOYSA-N 0.000 claims description 2
- 229910052769 Ytterbium Inorganic materials 0.000 claims 1
- 230000003439 radiotherapeutic effect Effects 0.000 claims 1
- NAWDYIZEMPQZHO-UHFFFAOYSA-N ytterbium Chemical compound [Yb] NAWDYIZEMPQZHO-UHFFFAOYSA-N 0.000 claims 1
- 230000009920 chelation Effects 0.000 abstract description 85
- 125000001424 substituent group Chemical group 0.000 abstract description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 abstract description 10
- 238000002560 therapeutic procedure Methods 0.000 abstract description 6
- 238000002405 diagnostic procedure Methods 0.000 abstract description 3
- 239000011541 reaction mixture Substances 0.000 description 70
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 62
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 59
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
- 239000000243 solution Substances 0.000 description 53
- 239000002904 solvent Substances 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 47
- 239000000047 product Substances 0.000 description 35
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- 230000002829 reductive effect Effects 0.000 description 28
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- 238000003756 stirring Methods 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
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- 229960000583 acetic acid Drugs 0.000 description 21
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 20
- 238000010992 reflux Methods 0.000 description 19
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 230000007062 hydrolysis Effects 0.000 description 12
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 12
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- 229910000147 aluminium phosphate Inorganic materials 0.000 description 10
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 10
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- RAEOEMDZDMCHJA-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-[2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]ethyl]amino]acetic acid Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CCN(CC(O)=O)CC(O)=O)CC(O)=O RAEOEMDZDMCHJA-UHFFFAOYSA-N 0.000 description 5
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F13/00—Compounds containing elements of Groups 7 or 17 of the Periodic Table
- C07F13/005—Compounds without a metal-carbon linkage
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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
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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
- A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
- A61K51/0478—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group complexes from non-cyclic ligands, e.g. EDTA, MAG3
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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
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| US5965132A (en) | 1992-03-05 | 1999-10-12 | Board Of Regents, The University Of Texas System | Methods and compositions for targeting the vasculature of solid tumors |
| US6005083A (en) * | 1997-03-28 | 1999-12-21 | Neorx Corporation | Bridged aromatic substituted amine ligands with donor atoms |
| CA2331789C (en) | 1998-07-13 | 2013-09-10 | Board Of Regents, The University Of Texas System | Cancer treatment methods using therapeutic conjugates that bind to aminophospholipids |
| BR9911882A (pt) | 1998-07-13 | 2005-02-15 | Univ Texas | Processo de tratamento de câncer empregando anticorpos a aminofosfolipìdios |
| US6818213B1 (en) | 1998-07-13 | 2004-11-16 | Board Of Regents, The University Of Texas System | Cancer treatment compositions comprising therapeutic conjugates that bind to aminophospholipids |
| US6406693B1 (en) | 1998-07-13 | 2002-06-18 | Board Of Regents, The University Of Texas System | Cancer treatment methods using antibodies to aminophospholipids |
| US6239237B1 (en) * | 1999-04-22 | 2001-05-29 | Nova Chemicals (International) S.A. | Group 8, 9 or 10 transition metal catalyst for olefin polymerization |
| CA2371728C (en) | 1999-06-11 | 2009-06-02 | Neorx Corporation | High dose radionuclide complexes for bone marrow suppression |
| US7094885B2 (en) | 1999-07-11 | 2006-08-22 | Neorx Corporation | Skeletal-targeted radiation to treat bone-associated pathologies |
| US7067111B1 (en) | 1999-10-25 | 2006-06-27 | Board Of Regents, University Of Texas System | Ethylenedicysteine (EC)-drug conjugates, compositions and methods for tissue specific disease imaging |
| US6565828B2 (en) | 2000-04-07 | 2003-05-20 | Bristol-Myers Squibb Company | Macrocyclic chelants for metallopharmaceuticals |
| CA2410906C (en) | 2000-06-02 | 2012-10-02 | Board Of Regents, The University Of Texas System | Ethylenedicysteine (ec)-drug conjugates |
| WO2002062398A2 (en) | 2001-01-08 | 2002-08-15 | Neorx Corporation | Radioactively labelled conjugates of phosphonates |
| ITRM20010079A1 (it) | 2001-02-16 | 2002-08-16 | Sigma Tau Ind Farmaceuti | Amminoderivati della biotina e loro coniugati con chelanti macrociclici. |
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| US6890513B2 (en) | 2001-05-25 | 2005-05-10 | Mcmaster University | Metal-carborane complexes for radioimaging and radiotherapy and methods for their preparation |
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| US8758723B2 (en) | 2006-04-19 | 2014-06-24 | The Board Of Regents Of The University Of Texas System | Compositions and methods for cellular imaging and therapy |
| US10925977B2 (en) | 2006-10-05 | 2021-02-23 | Ceil>Point, LLC | Efficient synthesis of chelators for nuclear imaging and radiotherapy: compositions and applications |
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-
1997
- 1997-03-28 US US08/829,533 patent/US6005083A/en not_active Expired - Lifetime
-
1998
- 1998-03-26 JP JP54176898A patent/JP2002500629A/ja not_active Ceased
- 1998-03-26 ES ES98912032T patent/ES2281927T3/es not_active Expired - Lifetime
- 1998-03-26 WO PCT/US1998/005858 patent/WO1998043678A2/en not_active Ceased
- 1998-03-26 EP EP98912032A patent/EP0971748B1/en not_active Expired - Lifetime
- 1998-03-26 EP EP07001523A patent/EP1813607A3/en not_active Withdrawn
- 1998-03-26 DE DE69837038T patent/DE69837038T2/de not_active Expired - Lifetime
- 1998-03-26 CA CA002284653A patent/CA2284653C/en not_active Expired - Fee Related
-
1999
- 1999-05-12 US US09/310,900 patent/US6177551B1/en not_active Expired - Fee Related
- 1999-05-12 US US09/310,455 patent/US6187910B1/en not_active Expired - Fee Related
-
2000
- 2000-11-28 US US09/724,834 patent/US6528627B1/en not_active Expired - Fee Related
-
2003
- 2003-01-17 US US10/346,311 patent/US6936700B2/en not_active Expired - Fee Related
-
2005
- 2005-02-18 US US11/061,110 patent/US7268220B2/en not_active Expired - Fee Related
-
2007
- 2007-09-04 US US11/849,769 patent/US7674886B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US6177551B1 (en) | 2001-01-23 |
| US6005083A (en) | 1999-12-21 |
| DE69837038D1 (de) | 2007-03-22 |
| WO1998043678A3 (en) | 1999-03-04 |
| US6187910B1 (en) | 2001-02-13 |
| JP2002500629A (ja) | 2002-01-08 |
| EP1813607A3 (en) | 2007-08-15 |
| CA2284653C (en) | 2008-07-29 |
| US7674886B2 (en) | 2010-03-09 |
| EP0971748B1 (en) | 2007-02-07 |
| CA2284653A1 (en) | 1998-10-08 |
| WO1998043678A2 (en) | 1998-10-08 |
| US6528627B1 (en) | 2003-03-04 |
| EP0971748A2 (en) | 2000-01-19 |
| US20030158393A1 (en) | 2003-08-21 |
| WO1998043678B1 (en) | 1999-04-01 |
| DE69837038T2 (de) | 2007-07-12 |
| US6936700B2 (en) | 2005-08-30 |
| EP1813607A2 (en) | 2007-08-01 |
| US20050276754A1 (en) | 2005-12-15 |
| US20080227961A1 (en) | 2008-09-18 |
| US7268220B2 (en) | 2007-09-11 |
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