JP2020533284A - ガドブトロール中間体及びこれを用いたガドブトロールの製造方法 - Google Patents
ガドブトロール中間体及びこれを用いたガドブトロールの製造方法 Download PDFInfo
- Publication number
- JP2020533284A JP2020533284A JP2020512644A JP2020512644A JP2020533284A JP 2020533284 A JP2020533284 A JP 2020533284A JP 2020512644 A JP2020512644 A JP 2020512644A JP 2020512644 A JP2020512644 A JP 2020512644A JP 2020533284 A JP2020533284 A JP 2020533284A
- Authority
- JP
- Japan
- Prior art keywords
- chemical formula
- gadobutrol
- represented
- producing
- lithium
- 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.)
- Granted
Links
- 229960003411 gadobutrol Drugs 0.000 title claims abstract description 56
- ZPDFIIGFYAHNSK-CTHHTMFSSA-K 2-[4,10-bis(carboxylatomethyl)-7-[(2r,3s)-1,3,4-trihydroxybutan-2-yl]-1,4,7,10-tetrazacyclododec-1-yl]acetate;gadolinium(3+) Chemical compound [Gd+3].OC[C@@H](O)[C@@H](CO)N1CCN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)CC1 ZPDFIIGFYAHNSK-CTHHTMFSSA-K 0.000 title claims abstract description 55
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 19
- 239000000126 substance Substances 0.000 claims abstract description 61
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 21
- -1 lithium halogen Chemical class 0.000 claims description 19
- 229910052744 lithium Inorganic materials 0.000 claims description 14
- QBPPRVHXOZRESW-UHFFFAOYSA-N 1,4,7,10-tetraazacyclododecane Chemical compound C1CNCCNCCNCCN1 QBPPRVHXOZRESW-UHFFFAOYSA-N 0.000 claims description 8
- JZNZSKXIEDHOBD-HUUCEWRRSA-N 2-[4,10-bis(carboxymethyl)-7-[(2r,3s)-1,3,4-trihydroxybutan-2-yl]-1,4,7,10-tetrazacyclododec-1-yl]acetic acid Chemical compound OC[C@@H](O)[C@@H](CO)N1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1 JZNZSKXIEDHOBD-HUUCEWRRSA-N 0.000 claims description 7
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims description 7
- 150000001875 compounds Chemical class 0.000 claims description 7
- 239000007795 chemical reaction product Substances 0.000 claims description 6
- 229940106681 chloroacetic acid Drugs 0.000 claims description 6
- 229940075613 gadolinium oxide Drugs 0.000 claims description 6
- 229910001938 gadolinium oxide Inorganic materials 0.000 claims description 6
- CMIHHWBVHJVIGI-UHFFFAOYSA-N gadolinium(iii) oxide Chemical compound [O-2].[O-2].[O-2].[Gd+3].[Gd+3] CMIHHWBVHJVIGI-UHFFFAOYSA-N 0.000 claims description 6
- 238000001728 nano-filtration Methods 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 3
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 claims description 3
- 230000002152 alkylating effect Effects 0.000 claims description 2
- 239000002616 MRI contrast agent Substances 0.000 abstract description 6
- 230000002194 synthesizing effect Effects 0.000 abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229910052688 Gadolinium Inorganic materials 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000008213 purified water Substances 0.000 description 5
- ILJSQTXMGCGYMG-UHFFFAOYSA-N triacetic acid Chemical compound CC(=O)CC(=O)CC(O)=O ILJSQTXMGCGYMG-UHFFFAOYSA-N 0.000 description 5
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 238000004886 process control Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- GEKNCWQQNMEIMS-UHFFFAOYSA-N 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane Chemical compound C1OC(C)(C)OCC2OC21 GEKNCWQQNMEIMS-UHFFFAOYSA-N 0.000 description 3
- GTTSNKDQDACYLV-UHFFFAOYSA-N Trihydroxybutane Chemical group CCCC(O)(O)O GTTSNKDQDACYLV-UHFFFAOYSA-N 0.000 description 3
- 239000001273 butane Substances 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- ZPDFIIGFYAHNSK-UHFFFAOYSA-K gadobutrol Chemical compound [Gd+3].OCC(O)C(CO)N1CCN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)CC1 ZPDFIIGFYAHNSK-UHFFFAOYSA-K 0.000 description 3
- 239000003456 ion exchange resin Substances 0.000 description 3
- 229920003303 ion-exchange polymer Polymers 0.000 description 3
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 3
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 3
- RRBYUSWBLVXTQN-UHFFFAOYSA-N tricyclene Chemical compound C12CC3CC2C1(C)C3(C)C RRBYUSWBLVXTQN-UHFFFAOYSA-N 0.000 description 3
- RRBYUSWBLVXTQN-VZCHMASFSA-N tricyclene Natural products C([C@@H]12)C3C[C@H]1C2(C)C3(C)C RRBYUSWBLVXTQN-VZCHMASFSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- KPZGRMZPZLOPBS-UHFFFAOYSA-N 1,3-dichloro-2,2-bis(chloromethyl)propane Chemical compound ClCC(CCl)(CCl)CCl KPZGRMZPZLOPBS-UHFFFAOYSA-N 0.000 description 1
- FYFSGGAVTBSKBV-UHFFFAOYSA-N 3-(1,4,7,10-tetrazacyclododec-1-yl)butane-1,2,4-triol;tetrahydrochloride Chemical compound Cl.Cl.Cl.Cl.OCC(O)C(CO)N1CCNCCNCCNCC1 FYFSGGAVTBSKBV-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 0 CC(*1CCNCCNCCNCC1)C(CO)=O Chemical compound CC(*1CCNCCNCCNCC1)C(CO)=O 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 206010024769 Local reaction Diseases 0.000 description 1
- SRKRRRXSZPZDNB-UHFFFAOYSA-N N1(CCNCCNCCNCC1)C(CC)C Chemical compound N1(CCNCCNCCNCC1)C(CC)C SRKRRRXSZPZDNB-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000002872 contrast media Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- RJOJUSXNYCILHH-UHFFFAOYSA-N gadolinium(3+) Chemical compound [Gd+3] RJOJUSXNYCILHH-UHFFFAOYSA-N 0.000 description 1
- LYQGMALGKYWNIU-UHFFFAOYSA-K gadolinium(3+);triacetate Chemical compound [Gd+3].CC([O-])=O.CC([O-])=O.CC([O-])=O LYQGMALGKYWNIU-UHFFFAOYSA-K 0.000 description 1
- LGMLJQFQKXPRGA-VPVMAENOSA-K gadopentetate dimeglumine Chemical compound [Gd+3].CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O LGMLJQFQKXPRGA-VPVMAENOSA-K 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 230000036244 malformation Effects 0.000 description 1
- 210000001161 mammalian embryo Anatomy 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000001223 reverse osmosis Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
- A61K49/106—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
- A61K49/106—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA
- A61K49/108—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA the metal complex being Gd-DOTA
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
-
- 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
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Radiology & Medical Imaging (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
Claims (6)
- 前記塩酸の使用量は、化学式1で表されるリチウムハロゲン錯体に対して、4.0乃至4.2当量である、請求項2に記載のガドブトロール中間体の製造方法。
- 前記化学式1で表されるリチウムハロゲン錯体と塩酸の反応物を濾過して化学式2で表されるガドブトロール中間体を結晶形態で得る段階を更に含む、請求項2に記載のガドブトロール中間体の製造方法。
- 前記ガドブトロール中間体とクロロ酢酸の反応物を、ナノフィルトレーションシステムを利用して100乃至300ダルトン(Dalton)に該当する塩及び水溶性低分子物質を濾過して精製する段階を更に含む、請求項5に記載のガドブトロールの製造方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020170109677A KR101971435B1 (ko) | 2017-08-29 | 2017-08-29 | 가도부트롤 중간체 및 이를 이용한 가도부트롤의 제조 방법 |
KR10-2017-0109677 | 2017-08-29 | ||
PCT/KR2018/009956 WO2019045436A1 (ko) | 2017-08-29 | 2018-08-29 | 가도부트롤 중간체 및 이를 이용한 가도부트롤의 제조 방법 |
Publications (2)
Publication Number | Publication Date |
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JP2020533284A true JP2020533284A (ja) | 2020-11-19 |
JP6967143B2 JP6967143B2 (ja) | 2021-11-17 |
Family
ID=65525913
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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JP2020512644A Active JP6967143B2 (ja) | 2017-08-29 | 2018-08-29 | ガドブトロール中間体及びこれを用いたガドブトロールの製造方法 |
Country Status (10)
Country | Link |
---|---|
US (1) | US11091449B2 (ja) |
EP (1) | EP3677574B1 (ja) |
JP (1) | JP6967143B2 (ja) |
KR (1) | KR101971435B1 (ja) |
CN (1) | CN111065629A (ja) |
CA (1) | CA3074161C (ja) |
ES (1) | ES2965947T3 (ja) |
PL (1) | PL3677574T3 (ja) |
RU (1) | RU2740901C1 (ja) |
WO (1) | WO2019045436A1 (ja) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
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KR20210112910A (ko) * | 2020-03-06 | 2021-09-15 | 주식회사 엔지켐생명과학 | 가도부트롤 주사제 제조를 위한 부형제인 칼코부트롤의 제조 방법 |
CN113880850B (zh) * | 2021-10-18 | 2022-10-04 | 苏州百灵威超精细材料有限公司 | 一种钆布醇中间体及制备方法和在制备钆布醇中的应用 |
Citations (6)
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JPH07507067A (ja) * | 1992-06-04 | 1995-08-03 | シエーリング アクチエンゲゼルシヤフト | N−β−ヒドロキシアルキル−トリ−N−カルボキシアルキル−1,4,7,10−テトラアザシクロドデカン−及びN−β−ヒドロキシアルキル−トリ−N−カルボキシアルキル−1,4,8,11−テトラアザシクロテトラデカン−誘導体及びその金属錯体の製法 |
JP2002503238A (ja) * | 1997-06-11 | 2002-01-29 | ブラッコ・エッセ・ピ・ア | 1,4,7,10−テトラアザシクロドデカン−1,4,7−三酢酸及びその誘導体の調製のための方法 |
JP2013527212A (ja) * | 2010-06-04 | 2013-06-27 | バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | Dmfアセタールおよびn−メチルイミダゾールによる、ワンポット法でのガドブトロール製造 |
JP2014522387A (ja) * | 2011-04-21 | 2014-09-04 | バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 高純度ガドブトロールの製造 |
WO2016043462A2 (ko) * | 2014-09-17 | 2016-03-24 | 에스티팜 주식회사 | 칼코부트롤의 제조방법 |
WO2016105172A2 (en) * | 2014-12-26 | 2016-06-30 | St Pharm Co., Ltd. | A method for preparing gadobutrol |
Family Cites Families (10)
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DE4009119A1 (de) | 1990-03-19 | 1991-09-26 | Schering Ag | 1,4,7,10-tetraazacyclododecan-butyltriole, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische mittel |
US5539105A (en) * | 1990-08-29 | 1996-07-23 | Dibra S.P.A. | Intermediates for chelating agents with prefixed symmetry and process for their preparation |
DE19724186C2 (de) * | 1997-06-02 | 2002-07-18 | Schering Ag | Verfahren zur Mono- und 1,7-Bis-N-ß-Hydroxyalkylierung von Cyclen und die entsprechenden N-ß-Hydroxyalkyl-1,4,7,10-tetraazacyclododecan-Li-Salz-Komplexe |
IT1292128B1 (it) * | 1997-06-11 | 1999-01-25 | Bracco Spa | Processo per la preparazione di chelanti macrociclici e loro chelati con ioni metallici paramagnetici |
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WO2019045436A1 (ko) | 2019-03-07 |
EP3677574A4 (en) | 2021-08-11 |
KR20190025131A (ko) | 2019-03-11 |
EP3677574B1 (en) | 2023-10-11 |
CA3074161C (en) | 2022-04-05 |
PL3677574T3 (pl) | 2024-03-04 |
KR101971435B1 (ko) | 2019-04-24 |
CA3074161A1 (en) | 2019-03-07 |
US11091449B2 (en) | 2021-08-17 |
EP3677574A1 (en) | 2020-07-08 |
JP6967143B2 (ja) | 2021-11-17 |
ES2965947T3 (es) | 2024-04-17 |
RU2740901C1 (ru) | 2021-01-21 |
US20200181098A1 (en) | 2020-06-11 |
CN111065629A (zh) | 2020-04-24 |
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