KR920702234A - 생활성제용의 신규한 링커 - Google Patents
생활성제용의 신규한 링커Info
- Publication number
- KR920702234A KR920702234A KR1019920700754A KR920700754A KR920702234A KR 920702234 A KR920702234 A KR 920702234A KR 1019920700754 A KR1019920700754 A KR 1019920700754A KR 920700754 A KR920700754 A KR 920700754A KR 920702234 A KR920702234 A KR 920702234A
- Authority
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- South Korea
- Prior art keywords
- formula
- derivative
- compound
- general formula
- conjugate
- Prior art date
Links
- 239000012867 bioactive agent Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 18
- 238000000034 method Methods 0.000 claims 11
- 238000004519 manufacturing process Methods 0.000 claims 6
- 238000009833 condensation Methods 0.000 claims 5
- 230000005494 condensation Effects 0.000 claims 5
- -1 piperazinyl carbonyl residue Chemical group 0.000 claims 5
- 239000000126 substance Substances 0.000 claims 5
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 claims 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims 3
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 3
- 239000000427 antigen Substances 0.000 claims 3
- 102000036639 antigens Human genes 0.000 claims 3
- 108091007433 antigens Proteins 0.000 claims 3
- 239000003795 chemical substances by application Substances 0.000 claims 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims 2
- 230000004913 activation Effects 0.000 claims 2
- 150000001412 amines Chemical class 0.000 claims 2
- 125000003277 amino group Chemical group 0.000 claims 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 2
- 210000004027 cell Anatomy 0.000 claims 2
- 239000012634 fragment Substances 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 239000001257 hydrogen Substances 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 125000006239 protecting group Chemical group 0.000 claims 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
- 206010005003 Bladder cancer Diseases 0.000 claims 1
- 206010006187 Breast cancer Diseases 0.000 claims 1
- 208000026310 Breast neoplasm Diseases 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 206010033128 Ovarian cancer Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 210000001744 T-lymphocyte Anatomy 0.000 claims 1
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 1
- 230000003213 activating effect Effects 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- IBVAQQYNSHJXBV-UHFFFAOYSA-N adipic acid dihydrazide Chemical class NNC(=O)CCCCC(=O)NN IBVAQQYNSHJXBV-UHFFFAOYSA-N 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 229940045799 anthracyclines and related substance Drugs 0.000 claims 1
- 230000001093 anti-cancer Effects 0.000 claims 1
- 230000003127 anti-melanomic effect Effects 0.000 claims 1
- HCOMFAYPHBFMKU-UHFFFAOYSA-N butanedihydrazide Chemical compound NNC(=O)CCC(=O)NN HCOMFAYPHBFMKU-UHFFFAOYSA-N 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 229960004679 doxorubicin Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims 1
- 239000003102 growth factor Substances 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 229910052740 iodine Inorganic materials 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 108020003175 receptors Proteins 0.000 claims 1
- 102000005962 receptors Human genes 0.000 claims 1
- 239000010979 ruby Substances 0.000 claims 1
- 229910001750 ruby Inorganic materials 0.000 claims 1
- 238000000926 separation method Methods 0.000 claims 1
- 150000003573 thiols Chemical class 0.000 claims 1
- 210000004881 tumor cell Anatomy 0.000 claims 1
- 239000000439 tumor marker Substances 0.000 claims 1
- 201000005112 urinary bladder cancer Diseases 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/24—Condensed ring systems having three or more rings
- C07H15/252—Naphthacene radicals, e.g. daunomycins, adriamycins
-
- 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
-
- 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
- A61K47/56—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/58—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 organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
-
- 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
- A61K47/62—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 a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
-
- 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
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/6807—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug or compound being a sugar, nucleoside, nucleotide, nucleic acid, e.g. RNA antisense
- A61K47/6809—Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin
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- 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
- A61K47/6835—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 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6883—Polymer-drug antibody conjugates, e.g. mitomycin-dextran-Ab; DNA-polylysine-antibody complex or conjugate used for therapy
-
- 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
- A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
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- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/24—Heterocyclic radicals containing oxygen or sulfur as ring hetero atom
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- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Immunology (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
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Abstract
내용 없음
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
Claims (50)
- 일반식(1)의 접합체.
- [A-O-W-Z]a-T (1)
- 상기식에서 잔기 A-O-는 일반식 A-O-H의 약제[여기서, -O-H는 1차 또는 2차 하이드록실 그룹이다]의 잔사이고, a는 1내지 30의 정수이고, W는 일반식(2)
-
- 의 그룹[여기서, b는 1 내지 4의 정수이고, B는 C1-C3알킬렌 그룹이며, R1및 R2는 각각 독립적으로 수소, 할로겐, 알킬, 페닐 또는 치환된 페닐을 나타낸다]이고, Z는 분리 그룹이며, T는 담체 성분이다.
- 제1항에 있어서, 잔기 A-O-가 일반식 A-O-H의 안트라사이클린으로부터 유도된 접합체.
- 제1항에 있어서, 잔기 A-O-가 하기 일반식으로 표시되는 접합체.
-
- 상기 식에서 R10는 수소원자이거나 하이드록시 또는 메톡시 그룹이고, R11및 R12중의 하나는 수소원자이며 다른 하나는 하이드록실 그룹이거나, R11은 수소 또는 요오드 원자이고, R12는 수소원자이며, R13는 아미노 그룹이거나, 모르폴리노 환에 포함된 질소원자이다.
- 제1항에 있어서, a가 1내지 5의 정수인 접합체.
- 제1항에 있어서, B가 -(CH2)2-인 접합체.
- 제1항에 있어서, Z가 (Ⅰ)-NH-; (Ⅱ)-NH-(CH2)c-S-S[여기서, c는 1내지 4의 정수이다]; (Ⅲ)-NH-[C]d-N=CH-[여기서, (a)는 d는 0이고 (b)d는 1이며, [C]는 -NH-CO(CH2)e-CO-NH-(여기서, e는 2내지 4의 정수이다)이고, (c)는 d는 1내지 4의 정수이며 [C]는 -(CH2)f-O-(CH2)f-(여기서, f는 1 또는 2이다)이거나, (d)d는 2 내지 6의 정수이며, [C]는 CH2이다]; (Ⅳ)-CH-[C]d-NH-CO[여기서 [C]및 d는 상기한 바와같다]; (Ⅴ)-[D]-NH-[여기서, [D]는 -NH-[CH2]g-(여기서, g는 2 내지 6의 정수이다)]; (Ⅵ)-[E]-CO-[여기서, [E]는 -NH-(CH2)g-NH-(여기서, g는 2 내지 6의 정수이다)이다]; 또는 (Ⅶ)일반식피페라지닐 카보닐 잔기인 접합체.
- 제1항에 있어서, 담체성분 T가 항원과 관련된 종양에 결합될 수 있는, 항원 부위를 함유하는 다세포항체 또는 이의 단편, 종량 세포 개체군 상에 바람직하게 또는 선택적으로 발현된 항원에 결합될 수 있는, 항원 결합 부위를 함유하는 단세포 항체 또는 이의 단편; 종양 세포에 바람직하게 또는 선택적으로 결합될 수 있는 펩티드 단백질로부터 선택된 접합체.
- 제7항에 있어서, 담체 성분 T가 항 T-세포 항체 항 CD5항체, 항 트랜스페인 수용체 항체, 항 흑색종 항체, 항 암 표지 항체, 항 난소암항체, 항 유방암 항체 및 항 방광암항체로부터 선택된 접합체.
- 제7항에 있어서, 담체 성분 T가 성장 인자인 접합체.
- 일반식(3)의 유도체를 제1항에서 정의한 바와같은 분리 그룹 Z및 담체 성분 T를 제공할 수 있는 물질 또는 물질들과 축합시킴으로써 접합체를 형성시킴을 포함하며, 제1항에서 정의한 바와같은 일반식(1)의 접합체를 제조하는 방법.
- A-O-W-OH (3)
- 상기 식에서 A-O- 및 W는 제1항에서 정의한 바와같다.
- 제10항에 있어서, 축합이 일반식(3)의 유도체의 활성화 유도체를 통하거나 축합제의 존재하에 직접 반응시킴으로써 수행되는 방법.
- 제10항에 있어서, 일반식(3)의 유도체를 일반식(4)A-O-W-L의 활성화 유도체[여기서, A-O-및 W는 제10항에서 정의한 바와같고, L은 아미드 결합을 형성시키기 위한 활성화 그룹이다]로 전환시키고 (Ⅰ')일반식 (4)의 생성 화합물을 일반식 T[NH2]x의 물질[여기서, T는 담체 성분이고, X는 축합에 이용할 수 있는 아미노 그룹의 수이다]과 축합시키거나, (Ⅱ')일반식(4)의 화합물을 일반NH-2(CH2)c-SH의 티올 유도체[여기서, c는 1 내지 4의 정수이다]와 축합시킨 다음 일반식(5)A-O-W-NH-(CH2)c-SH의 생성화합물[여기서, A-O, W 및 c는 상기한 바와같다]을 일반식 T-[SH]x1의 물질[여기서, T는 상기한 바와같다]과 축합시키거나, (Ⅲ')일반식(4)의 화합물을 히드라진, 석신산 또는 아디프산 디하이드라지드 유도체 또는 디아미노 화합물과 반응시킨 다음, 일반식(6)A-O-W-NH-[C]d-NH2의 생성 화합물[여기서, A-O 및 W는 제1항에서 정의한 바와같고[C]및 d는 제6항에서 정의한 바와같다]을 일반식 T-[CH]x2의 물질[여기서, T는 담체 성분이고, x2는 축합에 이용할 수 있는 포밀 그룹의 수이다]과 축합시킴을 포함하는 방법.
- 제10항에 있어서, (Ⅳ')제12항에서 기술한 바와같이 제조한 일반식(6)의 화합물을 임의로 축합제의 존재하에 일반식(7)의 물질과 축합시킴을 포함하는 방법.
- T-[CO-L']y (7)
- 상기 식에서 T-는 담체 성분이고, y는 1내지 30의 정수이며 담체 성분상의 카복실 그룹의 총 수를 나타내며, L'는 아미드 결합을 형성시키기 위한 하이드록시 또는 활성화 그룹이다.
- 제10항에 있어서, (Ⅴ')일반식(3)의 화합물을 일반식 H2N-[CH2]g-COOH의 아미노 유도체[여기서, g는 2내지 6의 정수이다]와 반응시킴으로써 일반식(8)의 유도체를 형성시키고, 임의로 일반식(8)의 화합물을 일반식(9)의 활성화 유도체로 전환시킨 다음, 일반식(9)의 생성 화합물 또는 일반식(8) 의 화합물을 축합제의 존재하에 제12항에서 정의한 바와같은 일반식 T-[NH2]x의 물질과 축합시킴을 포함하는 방법.
- A-O-W-[D]-OH (8)
- A-O-W-[D]-L (9)
- 상기 식에서, A-O-및 W는 제1항에서 정의한 바와같고, [D]는 제6항에서 정의한 바와같으며, L은 아미드 결합을 형성시키기 위한 활성화 그룹이다.
- 제10항에 있어서, (Ⅵ')일반식(4)이 화합물을 제6항에서 정의한 바와같은 일반식 H2N-(CH2)g-NH2의 아미노 유도체와 반응시킴으로써 일반식(10)의 유도체를 형성시키거나, (Ⅶ')일반식(4)의 화합물을 피페라진과 반응시켜 일반식(11)의 유도체를 형성시킨 다음, 상기한 바와같은 일반식(10) 또는 (11)의 화합물을 13항에서 기술한 바와같은 일반식(7)의 물질과 축합시킴을 포함하는 방법.
- A-O-W-[E]-H (10)
- A-O-W-[피페라진]-H (11)
- 상기 식에서 A-O, W 및 [E]는 상기한 바와같다.
- 약제학적으로 허용되는 담체 또는 희석제 및, 활성 성분으로서, 제1항에서 청구한 바와 같거나 제10항 내지 제15항중의 어느 한 항에서 청구한 바와같은 방법으로 제조할 접합체를 포함하는 약제학적 조성물.
- 제10항에 있어서, 기술한 바와같은 일반식(3)의 유도체.
- 제17항에 있어서, 14-O-(1-카복시메틸옥시-사이클로헥실)-3'-데아미노-3'-[2-(S)-메톡시-모르폴리닐]독소루비신인 유도체.
- 일반식 A-O-H의 약제[여기서, A-O-는 제1항에서 정의한 바와같다]를 일반식(12)의 화합물과 축합시킨 다음, 생성된 화합물로부터 보호그룹을 제거시킴을 포함하는, 제17항에서 청구한 바와같은 일반식(3)의 유도체의 제조방법.
-
- 상기 식에서 B,b,R1및 R2는 제1항에서 정의한 바와같고, R3은 보호그룹을 나타낸다.
- 제12항에 있어서, 정의한 바와같은 일반식(4)의 유도체.
- 제20항에 있어서, N-옥시석신이미딜 14-0-(1-카복시 메틸옥시-사이클로헥실)-3'-데아미노-3'-[2(S)-메톡시-4-모르폴리닐]독소루비신인 유도체.
- 제19항에서 청구된 바와같은 일반식(3)의 유도체를 일반식(4)의 유도체로 전환시킴을 포함하는, 제20항에서 청구한 바와 같은 일반식(4)의 유도체의 제조방법.
- 제12항에서 정의한 바와같은 일반식(5)의 유도체.
- 제1항에서 기술한 방법을 사용하여 일반식(3) 유도체로부터 일반식(5)의 유도체를 포함하는, 제23항에서 청구한 바와같은 일반식(5)의 유도체의 제조방법.
- 제12항에서 정의한 바와같은 일반식(6)의 유도체.
- 제25항에 있어서, 14-0-(1-하이드라지노카보닐메틸옥시-사이클로헥실)-3'-데아미노-3'-[2(S)-메톡시-4모르폴리닐]독수루비신인 유도체.
- 제12항에서 기술한 방법을 사용하여 일반식(3)의 유도체로부터 일반식(6)의 유도체를 제조함을 포함하는 제25항에서 청구한 바와같은 일반식(6)의 제조방법.
- 제14항에서 정의한 바와같은 일반식(9)의 유도체.
- 제1항에서 기술한 방법을 사용하여 일반식(3)의 유도체로부터 일반식(9)의 유도체를 포함하는, 제28항에서 청구한 바와같은 일반식(9)의 유도체의 제조방법.
- 제15항에서 정의한 바와같은 일반식 (10) 또는 (11)의 유도체.
- 제15항에서 기술한 방법을 사용하여 일반식(4)의 유도체로부터 일반식(10)또는 (11)의 유도체를 제조함을 포함하는, 제30항에서 청구한 바와같은 일반식(10) 또는 (11)의 유도체의 제조방법.
- ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
Applications Claiming Priority (3)
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| GB909017024A GB9017024D0 (en) | 1990-08-03 | 1990-08-03 | New linker for bioactive agents |
| PCT/EP1991/001449 WO1992002255A1 (en) | 1990-08-03 | 1991-08-01 | New linker for bioactive agents |
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| KR920702234A true KR920702234A (ko) | 1992-09-03 |
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| KR1019920700754A KR920702234A (ko) | 1990-08-03 | 1991-08-01 | 생활성제용의 신규한 링커 |
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| EP (1) | EP0495053B1 (ko) |
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| AT (1) | ATE135919T1 (ko) |
| AU (1) | AU650900B2 (ko) |
| CA (1) | CA2067184C (ko) |
| CS (1) | CS241491A3 (ko) |
| DE (1) | DE69118350T2 (ko) |
| DK (1) | DK0495053T3 (ko) |
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| FI (1) | FI100697B (ko) |
| GB (1) | GB9017024D0 (ko) |
| GR (1) | GR3019449T3 (ko) |
| HU (1) | HUT61898A (ko) |
| IE (1) | IE76467B1 (ko) |
| IL (2) | IL98986A (ko) |
| MY (1) | MY106526A (ko) |
| NO (1) | NO921287L (ko) |
| NZ (1) | NZ239165A (ko) |
| PH (1) | PH31048A (ko) |
| PT (1) | PT98545B (ko) |
| RU (1) | RU2116087C1 (ko) |
| TW (1) | TW211572B (ko) |
| WO (1) | WO1992002255A1 (ko) |
| YU (1) | YU48441B (ko) |
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-
1990
- 1990-08-03 GB GB909017024A patent/GB9017024D0/en active Pending
-
1991
- 1991-07-29 NZ NZ239165A patent/NZ239165A/xx unknown
- 1991-07-29 IL IL9898691A patent/IL98986A/en active IP Right Grant
- 1991-07-30 PH PH42855A patent/PH31048A/en unknown
- 1991-07-30 MY MYPI91001364A patent/MY106526A/en unknown
- 1991-07-31 ZA ZA916025A patent/ZA916025B/xx unknown
- 1991-07-31 TW TW080105996A patent/TW211572B/zh active
- 1991-08-01 DE DE69118350T patent/DE69118350T2/de not_active Expired - Fee Related
- 1991-08-01 DK DK91914151.5T patent/DK0495053T3/da active
- 1991-08-01 US US07/842,171 patent/US5387578A/en not_active Expired - Fee Related
- 1991-08-01 CA CA002067184A patent/CA2067184C/en not_active Expired - Fee Related
- 1991-08-01 KR KR1019920700754A patent/KR920702234A/ko not_active Application Discontinuation
- 1991-08-01 HU HU9201146A patent/HUT61898A/hu unknown
- 1991-08-01 JP JP51314491A patent/JP3169222B2/ja not_active Expired - Fee Related
- 1991-08-01 ES ES91914151T patent/ES2088013T3/es not_active Expired - Lifetime
- 1991-08-01 AT AT91914151T patent/ATE135919T1/de not_active IP Right Cessation
- 1991-08-01 WO PCT/EP1991/001449 patent/WO1992002255A1/en active IP Right Grant
- 1991-08-01 PT PT98545A patent/PT98545B/pt not_active IP Right Cessation
- 1991-08-01 AU AU83113/91A patent/AU650900B2/en not_active Ceased
- 1991-08-01 RU SU5011981A patent/RU2116087C1/ru active
- 1991-08-01 EP EP91914151A patent/EP0495053B1/en not_active Expired - Lifetime
- 1991-08-02 CS CS912414A patent/CS241491A3/cs unknown
- 1991-08-02 IE IE275791A patent/IE76467B1/en not_active IP Right Cessation
- 1991-08-02 CN CN91105270A patent/CN1058598A/zh active Pending
- 1991-08-02 YU YU134691A patent/YU48441B/sh unknown
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1992
- 1992-04-02 NO NO92921287A patent/NO921287L/no unknown
- 1992-04-02 FI FI921451A patent/FI100697B/fi active
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1994
- 1994-10-25 US US08/328,697 patent/US5547667A/en not_active Expired - Fee Related
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1995
- 1995-03-23 IL IL11310195A patent/IL113101A0/xx not_active IP Right Cessation
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1996
- 1996-03-28 GR GR960400748T patent/GR3019449T3/el unknown
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