JP6525968B2 - トランス−ジ−n−ピコリネートテトラアザシクロアルカンベースの鉛(ii)およびビスマス(iii)のキレート - Google Patents
トランス−ジ−n−ピコリネートテトラアザシクロアルカンベースの鉛(ii)およびビスマス(iii)のキレート Download PDFInfo
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- JP6525968B2 JP6525968B2 JP2016517605A JP2016517605A JP6525968B2 JP 6525968 B2 JP6525968 B2 JP 6525968B2 JP 2016517605 A JP2016517605 A JP 2016517605A JP 2016517605 A JP2016517605 A JP 2016517605A JP 6525968 B2 JP6525968 B2 JP 6525968B2
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- dodpa
- lead
- bismuth
- chelate
- ligand
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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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/94—Bismuth compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
-
- 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
- A61K51/0474—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
- A61K51/0482—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 chelates from cyclic ligands, e.g. DOTA
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/04—Chelating agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/24—Lead compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
Description
前記配位子は式A:
nは、0または1と等しく、
Rは、HまたはC1〜C18アルキル基であり、
R’は、HまたはC1〜C18アルキル基である。)
に対応し、
前記金属カチオンは、鉛(II)およびビスマス(III)からなる群より選択される金属のカチオンである。
また、RまたはR’がアルキル基の場合、RまたはR’は、C1〜C6アルキル基であることが好ましい。
DODPAおよびMe−DODPA配位子は、A. Rodriguez-Rodriguez, D. Esteban-Gomez, A. De Blas, T. Rodriguez-Blas, M. Fekete, M. Botta, R. Tripier, Platas-Iglesias, Inorg. Chem., 2012, 51, 2509-2521に示される方法によって合成することができる。
DODPAおよびMe−DODPA配位子の鉛およびビスマスとの錯体形成を、図式2にて以下に示す方法により行った。
結晶構造
結晶[Pb(Me)DODPA]および[Bi(Me−DODPA)](NO3).H2Oは、単離された錯体の水溶液をゆっくり蒸発させることによって得られた。そのX線構造をそれぞれ、図1および図2に示す。
鉛(II)とのDODPAまたはMe−DODPAキレートについて、熱力学的な安定性の定数pKを、25℃で濃度が0.10MのKNO3中で、電位差の測定によって直接的に確認した。pK定数は、キレート[Pb(Me−DODPA)]に関して18.74であり、キレートPb(DODPA)に関して17.09であることを確認した。しかしながら、これらのpKの値は、この化合物が異なる塩基度を有する限り、先行技術のキレートPb(DOTA)の値と比較することはできなかった。よって、キレートになっていない鉛の濃度に対応するpM値を、鉛(II)とのDODPAまたはMe−DODPAキレートに関して算出し、鉛(II)とのDOTAキレートに関する既知の値と比較することとした。この値pMは、Pb(II)の濃度が10μMおよび10倍の高配位子濃度で、pH7.4における遊離金属濃度の負の対数によって定義した。pM値は、DODPAと鉛(II)のキレート関しては12.3と測定され、Me−DODPAと鉛(II)のキレートに関して14.9と測定された。一方、DOTAと鉛(II)の錯体に関する既知のpM値は、18.4である。
ビスマス(III)および鉛(II)とのMe−DODPAキレートの錯体形成の反応速度をUV/Vis分光測定により調査した。
このキレートの標識化を、薄層クロマトグラフフィー(TLC)(溶離液:MeOH/NH4Cl(20%);1/1)およびKromasil C18カラムを使用した逆相高速液体クロマトグラフィー(HPLC)(20分間のTFA(0.01%の水)−CH3CNの直線グラジエント)により評価し、その活性をNaIガンマシンチレーターにより検出した。
Claims (3)
- トランス−ジ−N−ピコリネートテトラアザシクロアルカン配位子と金属カチオンとの錯体形成により生じたキレートであって、
前記配位子が下記式A:
nは、0と等しく、
RおよびR’は、メチル基である。)
によって表され、
前記金属カチオンが、鉛(II)およびビスマス(III)からなる群より選択される金属のカチオンである、キレート。 - 前記金属が、212Pb、212Biおよび213Biからなる群より選択される放射性同位元素であることを特徴とする、請求項1に記載のキレート。
- 鉛(II)を捕捉するための、請求項1または2に記載の配位子の使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR1355212 | 2013-06-06 | ||
FR1355212A FR3006688B1 (fr) | 2013-06-06 | 2013-06-06 | Chelates du plomb (ii) et du bismuth (iii) a base de tetraazacycloalcanes trans-di-n-picolinates |
PCT/EP2014/061723 WO2014195416A1 (fr) | 2013-06-06 | 2014-06-05 | Chélates du plomb (ii) et du bismuth (iii) à base de tétraazacycloalcanes trans-di-n- picolinates |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2016537309A JP2016537309A (ja) | 2016-12-01 |
JP6525968B2 true JP6525968B2 (ja) | 2019-06-05 |
Family
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JP2016517605A Active JP6525968B2 (ja) | 2013-06-06 | 2014-06-05 | トランス−ジ−n−ピコリネートテトラアザシクロアルカンベースの鉛(ii)およびビスマス(iii)のキレート |
Country Status (6)
Country | Link |
---|---|
US (1) | US9884881B2 (ja) |
EP (1) | EP3004075A1 (ja) |
JP (1) | JP6525968B2 (ja) |
CA (1) | CA2914537C (ja) |
FR (1) | FR3006688B1 (ja) |
WO (1) | WO2014195416A1 (ja) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3029032A1 (en) * | 2014-12-05 | 2016-06-08 | Centre National de la Recherche Scientifique (CNRS) | Bifunctional do2pa derivatives, chelates with metallic cations and use thereof |
EP3551231A4 (en) | 2016-12-08 | 2020-08-12 | The Brigham and Women's Hospital, Inc. | BISMUTH GADOLINIUM NANOPARTICLE |
FR3065883A1 (fr) * | 2017-05-06 | 2018-11-09 | Polyvalan Sas | Nouveaux complexes d’ions metalliques pour la cristallisation de macromolecules biologiques et la determination de leur structure cristallographique |
ES2759316B2 (es) * | 2018-11-07 | 2020-09-15 | Univ Coruna | Ligandos tetraazamacrociclicos y los correspondientes complejos de niquel utiles como agentes de contraste |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE68925904T2 (de) * | 1988-05-25 | 1996-10-31 | Us Commerce | Makrocyclische chelate und verwendungsverfahren |
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2013
- 2013-06-06 FR FR1355212A patent/FR3006688B1/fr active Active
-
2014
- 2014-06-05 WO PCT/EP2014/061723 patent/WO2014195416A1/fr active Application Filing
- 2014-06-05 EP EP14727858.4A patent/EP3004075A1/fr active Pending
- 2014-06-05 JP JP2016517605A patent/JP6525968B2/ja active Active
- 2014-06-05 US US14/895,990 patent/US9884881B2/en active Active
- 2014-06-05 CA CA2914537A patent/CA2914537C/en active Active
Also Published As
Publication number | Publication date |
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CA2914537C (en) | 2021-02-23 |
US20160115187A1 (en) | 2016-04-28 |
JP2016537309A (ja) | 2016-12-01 |
FR3006688B1 (fr) | 2015-08-14 |
US9884881B2 (en) | 2018-02-06 |
FR3006688A1 (fr) | 2014-12-12 |
CA2914537A1 (en) | 2014-12-11 |
WO2014195416A1 (fr) | 2014-12-11 |
EP3004075A1 (fr) | 2016-04-13 |
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