CA2965196C - Preparations of meta-iodobenzylguanidine and precursors thereof - Google Patents
Preparations of meta-iodobenzylguanidine and precursors thereof Download PDFInfo
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- CA2965196C CA2965196C CA2965196A CA2965196A CA2965196C CA 2965196 C CA2965196 C CA 2965196C CA 2965196 A CA2965196 A CA 2965196A CA 2965196 A CA2965196 A CA 2965196A CA 2965196 C CA2965196 C CA 2965196C
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- 238000002360 preparation method Methods 0.000 title claims abstract description 320
- PDWUPXJEEYOOTR-UHFFFAOYSA-N 2-[(3-iodophenyl)methyl]guanidine Chemical compound NC(=N)NCC1=CC=CC(I)=C1 PDWUPXJEEYOOTR-UHFFFAOYSA-N 0.000 title claims abstract description 165
- 239000002243 precursor Substances 0.000 title abstract description 11
- 229920000642 polymer Polymers 0.000 claims abstract description 324
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims abstract description 173
- 239000012633 leachable Substances 0.000 claims abstract description 155
- 239000000178 monomer Substances 0.000 claims abstract description 139
- 150000003839 salts Chemical class 0.000 claims abstract description 98
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 126
- 238000000034 method Methods 0.000 claims description 124
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 114
- 239000000203 mixture Substances 0.000 claims description 105
- 239000008194 pharmaceutical composition Substances 0.000 claims description 60
- 150000001875 compounds Chemical class 0.000 claims description 54
- 239000002904 solvent Substances 0.000 claims description 54
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 45
- LQLOGZQVKUNBRX-UHFFFAOYSA-N (3-iodophenyl)methanamine Chemical compound NCC1=CC=CC(I)=C1 LQLOGZQVKUNBRX-UHFFFAOYSA-N 0.000 claims description 28
- 239000003960 organic solvent Substances 0.000 claims description 27
- 239000000463 material Substances 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
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- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 claims description 22
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
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- -1 halogen ion Chemical class 0.000 claims description 18
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- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 12
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- 238000004519 manufacturing process Methods 0.000 claims description 6
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- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 3
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- 229910052789 astatine Inorganic materials 0.000 claims description 3
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- 238000004458 analytical method Methods 0.000 description 46
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 35
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- 239000012535 impurity Substances 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- 239000002253 acid Substances 0.000 description 25
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- 238000001095 inductively coupled plasma mass spectrometry Methods 0.000 description 22
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- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 20
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- WCRDXYSYPCEIAK-UHFFFAOYSA-N dibutylstannane Chemical compound CCCC[SnH2]CCCC WCRDXYSYPCEIAK-UHFFFAOYSA-N 0.000 description 14
- 238000003384 imaging method Methods 0.000 description 14
- 230000009467 reduction Effects 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 12
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000005516 engineering process Methods 0.000 description 12
- 238000002347 injection Methods 0.000 description 12
- 239000007924 injection Substances 0.000 description 12
- PDWUPXJEEYOOTR-JRGAVVOBSA-N iobenguane (131I) Chemical compound NC(N)=NCC1=CC=CC([131I])=C1 PDWUPXJEEYOOTR-JRGAVVOBSA-N 0.000 description 12
- 239000011159 matrix material Substances 0.000 description 12
- 239000004033 plastic Substances 0.000 description 12
- 229920003023 plastic Polymers 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- 230000029087 digestion Effects 0.000 description 11
- 238000011194 good manufacturing practice Methods 0.000 description 11
- 239000008213 purified water Substances 0.000 description 11
- 239000013557 residual solvent Substances 0.000 description 11
- 239000012279 sodium borohydride Substances 0.000 description 11
- 229910000033 sodium borohydride Inorganic materials 0.000 description 11
- 239000012086 standard solution Substances 0.000 description 11
- 238000005406 washing Methods 0.000 description 11
- 206010061332 Paraganglion neoplasm Diseases 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- ABSNGNUGFQIDDO-UHFFFAOYSA-N 2-benzylguanidine Chemical compound NC(N)=NCC1=CC=CC=C1 ABSNGNUGFQIDDO-UHFFFAOYSA-N 0.000 description 9
- 238000002591 computed tomography Methods 0.000 description 9
- 238000011084 recovery Methods 0.000 description 9
- 239000012085 test solution Substances 0.000 description 9
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
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- 229910052740 iodine Inorganic materials 0.000 description 8
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- 238000003786 synthesis reaction Methods 0.000 description 8
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 7
- 229940127088 antihypertensive drug Drugs 0.000 description 7
- RJGHQTVXGKYATR-UHFFFAOYSA-L dibutyl(dichloro)stannane Chemical compound CCCC[Sn](Cl)(Cl)CCCC RJGHQTVXGKYATR-UHFFFAOYSA-L 0.000 description 7
- 238000004980 dosimetry Methods 0.000 description 7
- 239000011630 iodine Substances 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 6
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 6
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
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- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical group [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
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- 229940049964 oleate Drugs 0.000 description 1
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- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
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- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000005361 soda-lime glass Substances 0.000 description 1
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- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F230/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal
- C08F230/04—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal containing a metal
-
- 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
- A61K51/0404—Lipids, e.g. triglycerides; Polycationic carriers
- A61K51/0406—Amines, polyamines, e.g. spermine, spermidine, amino acids, (bis)guanidines
-
- 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
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C277/08—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups of substituted guanidines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/04—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton
- C07C279/06—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by halogen atoms, or by nitro or nitroso groups
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Optics & Photonics (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462068598P | 2014-10-24 | 2014-10-24 | |
| US62/068,598 | 2014-10-24 | ||
| US201462069029P | 2014-10-27 | 2014-10-27 | |
| US62/069,029 | 2014-10-27 | ||
| PCT/US2015/057222 WO2016065322A1 (en) | 2014-10-24 | 2015-10-23 | Preparations of meta-iodobenzylguanidine and precursors thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2965196A1 CA2965196A1 (en) | 2016-04-28 |
| CA2965196C true CA2965196C (en) | 2024-01-23 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2965196A Active CA2965196C (en) | 2014-10-24 | 2015-10-23 | Preparations of meta-iodobenzylguanidine and precursors thereof |
Country Status (8)
| Country | Link |
|---|---|
| US (4) | US20160115267A1 (enExample) |
| EP (2) | EP3268052B1 (enExample) |
| JP (3) | JP7078396B2 (enExample) |
| CN (1) | CN107106710A (enExample) |
| AU (3) | AU2015335599B2 (enExample) |
| CA (1) | CA2965196C (enExample) |
| ES (1) | ES2916550T3 (enExample) |
| WO (1) | WO2016065322A1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2015335599B2 (en) | 2014-10-24 | 2020-03-19 | Molecular Insight Pharmaceuticals, Inc. | Preparations of meta-iodobenzylguanidine and precursors thereof |
| CN109666039B (zh) * | 2018-12-13 | 2020-12-25 | 山西大学 | 一种五核锡（ii）化合物及其制备方法和应用 |
| TWI898889B (zh) * | 2024-10-22 | 2025-09-21 | 國家原子能科技研究院 | 不含保護基之間三正丁基錫苯甲胍的製造方法 |
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|---|---|---|---|---|
| US4591630A (en) * | 1981-07-30 | 1986-05-27 | Ethicon, Inc. | Annealed polydioxanone surgical device and method for producing the same |
| US5565185A (en) | 1994-07-20 | 1996-10-15 | Merck Frosst Canada, Inc. | Process for the preparation of radiolabeled meta-halobenzylguanidine |
| US7273601B2 (en) * | 2000-07-18 | 2007-09-25 | The University Of Western Ontario | Preparation of radiolabelled haloaromatics via polymer-bound intermediates |
| US6461585B1 (en) * | 1998-10-02 | 2002-10-08 | The University Of Western Ontario | Preparation of radiolabelled haloaromatics via polymer-bound intermediates |
| US7335347B2 (en) * | 2002-10-18 | 2008-02-26 | Mcmaster University | Methods for purifying radiolabelled compounds |
| GB0514087D0 (en) | 2005-07-11 | 2005-08-17 | Ge Healthcare Ltd | Stabilised radiopharmaceutical compositions |
| TWI606842B (zh) | 2010-05-11 | 2017-12-01 | 藍瑟斯醫學影像公司 | 用於合成及使用造影劑之組合物、方法及系統 |
| AU2015335599B2 (en) | 2014-10-24 | 2020-03-19 | Molecular Insight Pharmaceuticals, Inc. | Preparations of meta-iodobenzylguanidine and precursors thereof |
-
2015
- 2015-10-23 AU AU2015335599A patent/AU2015335599B2/en active Active
- 2015-10-23 US US14/921,898 patent/US20160115267A1/en not_active Abandoned
- 2015-10-23 CN CN201580064695.2A patent/CN107106710A/zh active Pending
- 2015-10-23 ES ES15825978T patent/ES2916550T3/es active Active
- 2015-10-23 EP EP15825978.8A patent/EP3268052B1/en active Active
- 2015-10-23 WO PCT/US2015/057222 patent/WO2016065322A1/en not_active Ceased
- 2015-10-23 EP EP21173328.2A patent/EP3888694A1/en not_active Withdrawn
- 2015-10-23 JP JP2017540977A patent/JP7078396B2/ja active Active
- 2015-10-23 CA CA2965196A patent/CA2965196C/en active Active
-
2019
- 2019-06-11 US US16/437,061 patent/US11279784B2/en active Active
-
2020
- 2020-05-28 JP JP2020093440A patent/JP7186744B2/ja active Active
- 2020-06-18 AU AU2020204062A patent/AU2020204062B9/en active Active
-
2022
- 2022-02-14 US US17/671,128 patent/US11840592B2/en active Active
- 2022-03-22 JP JP2022045482A patent/JP7399996B2/ja active Active
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| US20190367653A1 (en) | 2019-12-05 |
| AU2020204062A1 (en) | 2020-07-09 |
| JP2020143300A (ja) | 2020-09-10 |
| JP7078396B2 (ja) | 2022-05-31 |
| US11279784B2 (en) | 2022-03-22 |
| JP2022084797A (ja) | 2022-06-07 |
| JP2017534742A (ja) | 2017-11-24 |
| AU2015335599B2 (en) | 2020-03-19 |
| US20240174782A1 (en) | 2024-05-30 |
| AU2020204062B9 (en) | 2022-07-21 |
| HK1249425A1 (zh) | 2018-11-02 |
| WO2016065322A1 (en) | 2016-04-28 |
| EP3268052B1 (en) | 2021-06-23 |
| ES2916550T3 (es) | 2022-07-01 |
| AU2022204262A1 (en) | 2022-07-21 |
| CA2965196A1 (en) | 2016-04-28 |
| CN107106710A (zh) | 2017-08-29 |
| EP3268052A1 (en) | 2018-01-17 |
| US20230008878A1 (en) | 2023-01-12 |
| JP7399996B2 (ja) | 2023-12-18 |
| US11840592B2 (en) | 2023-12-12 |
| AU2020204062B2 (en) | 2022-07-07 |
| EP3888694A1 (en) | 2021-10-06 |
| AU2015335599A1 (en) | 2017-05-11 |
| JP7186744B2 (ja) | 2022-12-09 |
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