KR20030072627A - 비오틴의 아미노유도체 및 그의 마크로사이클릭킬레이트제와의 결합물 - Google Patents
비오틴의 아미노유도체 및 그의 마크로사이클릭킬레이트제와의 결합물 Download PDFInfo
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- KR20030072627A KR20030072627A KR10-2003-7010689A KR20037010689A KR20030072627A KR 20030072627 A KR20030072627 A KR 20030072627A KR 20037010689 A KR20037010689 A KR 20037010689A KR 20030072627 A KR20030072627 A KR 20030072627A
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- hydrogen
- biotin
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- 239000002738 chelating agent Substances 0.000 title description 9
- 125000004057 biotinyl group Chemical class [H]N1C(=O)N([H])[C@]2([H])[C@@]([H])(SC([H])([H])[C@]12[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(*)=O 0.000 title 1
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- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 2
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- 238000001959 radiotherapy Methods 0.000 claims description 2
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- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 53
- 239000011616 biotin Substances 0.000 description 40
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- 108090001008 Avidin Proteins 0.000 description 18
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
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- 125000006239 protecting group Chemical group 0.000 description 8
- -1 secondary-butyl Chemical group 0.000 description 8
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 7
- 125000003277 amino group Chemical group 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 6
- NAQMVNRVTILPCV-UHFFFAOYSA-N hexane-1,6-diamine Chemical compound NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 description 6
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- 238000012360 testing method Methods 0.000 description 6
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- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- QWVNTBHBRBLRRJ-YDHLFZDLSA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-n-(6-aminohexyl)pentanamide Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)NCCCCCCN)SC[C@@H]21 QWVNTBHBRBLRRJ-YDHLFZDLSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- 239000007821 HATU Substances 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
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- 229910021645 metal ion Inorganic materials 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 2
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- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
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- 102100026044 Biotinidase Human genes 0.000 description 1
- 108010039206 Biotinidase Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
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- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
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- 125000004427 diamine group Chemical group 0.000 description 1
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 150000003839 salts Chemical class 0.000 description 1
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- RVZPDKXEHIRFPM-UHFFFAOYSA-N tert-butyl n-(6-aminohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCCCCN RVZPDKXEHIRFPM-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K51/0497—Organic compounds conjugates with a carrier being an organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Optics & Photonics (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
아비딘/비오틴-DOTA 몰비 | ||
아비딘:비오틴 몰비 | 1:2 | 1:4 |
90Y-DOTA-비오틴(㎍) | 1 | 2 |
아비딘(㎍) | 51 | 51 |
결합율(%) | 99.8 | 99.7 |
비오틴에 대한 친화성 연구 | |||||
아비딘:비타민 H 몰비 | 1:2 | 1:4 | 1:8 | 1:16 | 1:32 |
90Y-DOTA-비오틴(㎍) | 0.25 | 0.25 | 0.25 | 0.25 | 0.25 |
커플링된 아비딘(㎍) | 6.4 | 6.4 | 6.4 | 6.4 | 6.4 |
첨가된 비오틴(㎍) | 0.047 | 0.094 | 0.188 | 0.376 | 0.752 |
치환율(%) | 0.2 | 0.0 | 0.8 | 0.0 | 0.0 |
Claims (9)
- 하기 화학식 I의 화합물:화학식 I상기 식에서,Q는 -(CH2)n- 그룹(이때 n은 4 내지 12의 정수이고, 이 경우에 R'는 존재하지 않는다)이거나, 또는Q는 -(CH2)a-CH(R')-(CH2)b-(이때 a 및 b는 독립적으로 0 내지 n의 정수이고, R'는 하기 정의하는 바와 같다)로 이루어진 그룹 중에서 선택되거나, 또는Q는 사이클로헥실, 페닐이고, 이 경우에 R'는 상기 사이클로헥실 또는 페닐 고리 상의 치환체이고;R은 수소 또는 -Λ이고, 이때 -Λ는 하기 화학식 II의 마크로사이클이고:화학식 II[상기 식에서,다양한 Y들은 동일하거나 상이할 수 있으며, 수소, 직쇄 또는 분지된 C1-C4알킬, -(CH2)m-COOH(여기에서 m은 1 내지 3의 정수이다)로 이루어진 그룹 중에서 선택되고;X는 수소 또는 -CH2-U 그룹(이때 U는 메틸, 에틸, p-아미노페닐 중에서 선택된다)이거나, 또는X는 -(CHW)o-Z 그룹(이때 o는 1 내지 5의 정수이고, W는 수소, 메틸 또는 에틸이고, Z는 O, N-R1(이때 R1은 수소 원자 또는 직쇄 또는 분지된 C1-C4알킬 그룹이다) 및 S 중에서 선택된 하나 이상의 헤테로원자를 함유하는 5 또는 6원의 헤테로사이클릭 그룹이거나, 또는 Z는 -NH2, -NH-C(=NH)-NH2및 -S-R2(이때 R2는 직쇄 또는 분지된 C1-C4알킬 그룹이다) 중에서 선택되고;p는 2 또는 3의 정수이다];R'는 수소, 직쇄 또는 분지된 C1-C4알킬, -(CH2)q-T(이때 T는 S-CH3, -OH 및 -COOH로 이루어진 그룹 중에서 선택되고, q는 1 또는 2의 정수이다)로 이루어진 그룹 중에서 선택되고;R"는 하기의 조건에 따라 R과 동일한 의미를 갖는다:R이 -Λ인 경우, R"는 수소이고; R이 수소인 경우 R"는 -Λ이거나, 또는 R 및 R"가 각각 -(CH2)r-Λ(R의 경우)(이때 r은 4 내지 12의 정수이다) 및 -Λ(R"의 경우)이고, 이때 Q는 -(CH2)n- 그룹이고, 이때 n은 4 내지 12의 정수이다.
- 치료 및/또는 진단용으로 유용한 화학식 I 화합물과 방사성 동위원소와의 복합체.
- 제 2 항에 있어서, 방사성 동위원소가 Fe-52, Mn-52m, Co-55, Cu-64, Ga-67, Ga-68, Tc-99m, In-111, I-123, I-125, I-131, P-32, Sc-47, Cu-67, Y-90, Pd-109, Ag-111, I-131, Pm-149, Re-186, Re-188, At-211, Bi-212, Bi-213, Rh-105, Sm-153, Lu-177 및 Au-198로 이루어지는 그룹 중에서 선택되는 복합체.
- 제 2 항 또는 제 3 항에 있어서, 화학식 I의 화합물에서 Q가 -(CH2)n-이고, 이때 n이 4 내지 8의 정수, 바람직하게는 6이고, Y가 -CH2-COOH이고 방사성 동위원소가 Y-90인 복합체.
- 제 1 항 또는 제 2 항의 화합물을 적합한 비히클 및/또는 부형제와의 혼합물로 함유하는 약학 및/또는 진단 조성물.
- 종양의 치료에 유용한 약물의 제조를 위한 제 1 항 또는 제 2 항에 따른 화합물의 용도.
- 제 2 항 내지 제 4 항 중 어느 하나의 항에 따른 복합체를 적합한 비히클 및/또는 부형제와의 혼합물로 함유하는 약학 및/또는 진단 조성물.
- 항암 방사성 의약품으로서 제 2 항 내지 제 4 항 중 어느 하나의 항에 따른 복합체의 용도.
- 구성요소들 중 적어도 하나 이상이 제 1 항 또는 제 2 항에 따른 화합물을함유함을 특징으로 하는, 종양의 방사선 요법 또는 진단을 위한 키트.
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IT2001RM000079A ITRM20010079A1 (it) | 2001-02-16 | 2001-02-16 | Amminoderivati della biotina e loro coniugati con chelanti macrociclici. |
ITRM01A000079 | 2001-02-16 | ||
PCT/IT2002/000091 WO2002066075A2 (en) | 2001-02-16 | 2002-02-15 | Biotin-derivatives and their conjugates with chelating agents |
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ITRM20040105A1 (it) | 2004-02-27 | 2004-05-27 | Tecnogen Scpa | Anticorpo monoclonale antitenascina umana. |
ITRM20050345A1 (it) * | 2005-06-30 | 2007-01-01 | Sigma Tau Ind Farmaceuti | Sintesi di deossi-biotinil esametilen diammina-dota. |
TWI381852B (zh) * | 2005-09-27 | 2013-01-11 | Sigma Tau Ind Farmaceuti | 生物素二胺基衍生物類及其與大環螯合劑之共軛物 |
ES2367675T3 (es) | 2007-04-04 | 2011-11-07 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Anticuerpo anti-epcam y usos del mismo. |
GB0922369D0 (en) | 2009-12-22 | 2010-02-03 | Hammersmith Imanet Ltd | Labelled biotin conjugates |
EP2630132A1 (en) * | 2010-10-22 | 2013-08-28 | Université de Strasbourg | Pochoxime conjugates useful for the treatment of hsp90 related pathologies |
CA2842276C (en) | 2011-08-02 | 2020-11-24 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Pharmaceutical composition of oxidised avidin suitable for inhalation |
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US5283342A (en) * | 1992-06-09 | 1994-02-01 | Neorx Corporation | Biotinylated small molecules |
US6075010A (en) * | 1992-06-09 | 2000-06-13 | Neorx Corporation | Small molecular weight ligand-hexose containing clearing agents |
US6416738B1 (en) * | 1973-12-07 | 2002-07-09 | Neorx Corporation | Pretargeting methods and compounds |
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IT1245748B (it) | 1990-12-21 | 1994-10-14 | Mini Ricerca Scient Tecnolog | Preparazione includente anticorpi monoclonali biotinilati, avidina e biotina, per la diagnosi di affezioni tumorali e suo impiego |
US5616690A (en) * | 1992-06-09 | 1997-04-01 | Neorx Corporation | Hexose derivatized human serum albumin clearing agents |
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US5976535A (en) * | 1992-06-09 | 1999-11-02 | Neorx Corporation | Pretargeting protocols for the enhanced localization of cytotoxins to target sites and cytotoxic combinations useful therefore |
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US5578287A (en) * | 1992-06-09 | 1996-11-26 | Neorx Corporation | Three-step pretargeting methods using improved biotin-active agent |
US6120768A (en) * | 1993-05-17 | 2000-09-19 | Immunomedics, Inc. | Dota-biotin derivatives |
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US5955605A (en) * | 1995-02-21 | 1999-09-21 | Neorx Corporation | Biotinidase resistant biotin-DOTA conjugates |
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US6005083A (en) | 1997-03-28 | 1999-12-21 | Neorx Corporation | Bridged aromatic substituted amine ligands with donor atoms |
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US8044081B2 (en) | 2011-10-25 |
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EP1359943A2 (en) | 2003-11-12 |
ATE306283T1 (de) | 2005-10-15 |
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MXPA03007317A (es) | 2004-06-30 |
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PL365279A1 (en) | 2004-12-27 |
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CN1531445A (zh) | 2004-09-22 |
WO2002066075A3 (en) | 2003-01-30 |
CZ305442B6 (cs) | 2015-09-23 |
PL202898B1 (pl) | 2009-08-31 |
DE60206599T2 (de) | 2006-06-22 |
JP4469133B2 (ja) | 2010-05-26 |
US20080085239A1 (en) | 2008-04-10 |
ITRM20010079A0 (it) | 2001-02-16 |
US7390828B2 (en) | 2008-06-24 |
CZ20031989A3 (cs) | 2004-02-18 |
HK1068251A1 (en) | 2005-04-29 |
HU229160B1 (hu) | 2013-09-30 |
ES2248522T3 (es) | 2006-03-16 |
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