JP2002503228A - デュオカルマイシンおよびｃｃ−１０６５の類似体 - Google Patents
デュオカルマイシンおよびｃｃ−１０６５の類似体Info
- Publication number
- JP2002503228A JP2002503228A JP55069798A JP55069798A JP2002503228A JP 2002503228 A JP2002503228 A JP 2002503228A JP 55069798 A JP55069798 A JP 55069798A JP 55069798 A JP55069798 A JP 55069798A JP 2002503228 A JP2002503228 A JP 2002503228A
- Authority
- JP
- Japan
- Prior art keywords
- alkylation
- ring
- dna
- mmol
- dsa
- 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.)
- Ceased
Links
- 229960005532 CC-1065 Drugs 0.000 title claims abstract description 18
- 229960005501 duocarmycin Drugs 0.000 title claims description 11
- VQNATVDKACXKTF-XELLLNAOSA-N duocarmycin Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C4=CC(=O)C5=C([C@@]64C[C@@H]6C3)C=C(N5)C(=O)OC)=CC2=C1 VQNATVDKACXKTF-XELLLNAOSA-N 0.000 title abstract description 40
- UOWVMDUEMSNCAV-WYENRQIDSA-N rachelmycin Chemical compound C1([C@]23C[C@@H]2CN1C(=O)C=1NC=2C(OC)=C(O)C4=C(C=2C=1)CCN4C(=O)C1=CC=2C=4CCN(C=4C(O)=C(C=2N1)OC)C(N)=O)=CC(=O)C1=C3C(C)=CN1 UOWVMDUEMSNCAV-WYENRQIDSA-N 0.000 title abstract description 14
- 229930184221 duocarmycin Natural products 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 47
- -1 N-substituted pyrrolidine ring Chemical group 0.000 claims description 71
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 10
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 10
- AZVARJHZBXHUSO-DZQVEHCYSA-N methyl (1R,4R,12S)-4-methyl-3,7-dioxo-10-(5,6,7-trimethoxy-1H-indole-2-carbonyl)-5,10-diazatetracyclo[7.4.0.01,12.02,6]trideca-2(6),8-diene-4-carboxylate Chemical compound COC1=C(OC)C(OC)=C2NC(C(=O)N3C[C@H]4C[C@]44C5=C(C(C=C43)=O)N[C@@](C5=O)(C)C(=O)OC)=CC2=C1 AZVARJHZBXHUSO-DZQVEHCYSA-N 0.000 claims description 7
- 230000004927 fusion Effects 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
- 229920002554 vinyl polymer Polymers 0.000 claims description 4
- 230000007118 DNA alkylation Effects 0.000 abstract description 109
- 230000000694 effects Effects 0.000 abstract description 21
- 230000000259 anti-tumor effect Effects 0.000 abstract description 5
- 230000003115 biocidal effect Effects 0.000 abstract 1
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- 150000001408 amides Chemical class 0.000 description 66
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 62
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- 108020004414 DNA Proteins 0.000 description 57
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- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 54
- 238000009739 binding Methods 0.000 description 50
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 48
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- 235000019439 ethyl acetate Nutrition 0.000 description 31
- 238000002474 experimental method Methods 0.000 description 29
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 28
- 238000002844 melting Methods 0.000 description 27
- 230000002829 reductive effect Effects 0.000 description 27
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 26
- 238000000034 method Methods 0.000 description 26
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- 239000000047 product Substances 0.000 description 24
- 230000004568 DNA-binding Effects 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- VQNATVDKACXKTF-UHFFFAOYSA-N Duocarmycin SA Natural products COC1=C(OC)C(OC)=C2NC(C(=O)N3C4=CC(=O)C5=C(C64CC6C3)C=C(N5)C(=O)OC)=CC2=C1 VQNATVDKACXKTF-UHFFFAOYSA-N 0.000 description 22
- 229960005510 duocarmycin SA Drugs 0.000 description 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 18
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- 230000008859 change Effects 0.000 description 18
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 18
- 230000001472 cytotoxic effect Effects 0.000 description 17
- 238000005935 nucleophilic addition reaction Methods 0.000 description 17
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 16
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- 229910052799 carbon Inorganic materials 0.000 description 13
- 239000012230 colorless oil Substances 0.000 description 13
- 238000004519 manufacturing process Methods 0.000 description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 13
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 12
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 12
- XYOVOXDWRFGKEX-UHFFFAOYSA-N azepine Chemical compound N1C=CC=CC=C1 XYOVOXDWRFGKEX-UHFFFAOYSA-N 0.000 description 12
- 239000010410 layer Substances 0.000 description 12
- PUPKPAZSFZOLOR-UHFFFAOYSA-N n,n-dimethylformamide;toluene Chemical compound CN(C)C=O.CC1=CC=CC=C1 PUPKPAZSFZOLOR-UHFFFAOYSA-N 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 11
- 238000003776 cleavage reaction Methods 0.000 description 11
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- 239000012044 organic layer Substances 0.000 description 11
- 230000007017 scission Effects 0.000 description 11
- 238000006265 spirocyclization reaction Methods 0.000 description 11
- WQPDQJCBHQPNCZ-UHFFFAOYSA-N cyclohexa-2,4-dien-1-one Chemical compound O=C1CC=CC=C1 WQPDQJCBHQPNCZ-UHFFFAOYSA-N 0.000 description 10
- 230000007423 decrease Effects 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 230000002152 alkylating effect Effects 0.000 description 9
- 238000005119 centrifugation Methods 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
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- 125000001424 substituent group Chemical group 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- RUFPHBVGCFYCNW-UHFFFAOYSA-N 1-naphthylamine Chemical compound C1=CC=C2C(N)=CC=CC2=C1 RUFPHBVGCFYCNW-UHFFFAOYSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 8
- 238000005859 coupling reaction Methods 0.000 description 8
- 238000000354 decomposition reaction Methods 0.000 description 8
- 230000001419 dependent effect Effects 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- AYYOZKHMSABVRP-UHFFFAOYSA-N methyl 1h-indole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C=CNC2=C1 AYYOZKHMSABVRP-UHFFFAOYSA-N 0.000 description 8
- 239000012038 nucleophile Substances 0.000 description 8
- 239000008363 phosphate buffer Substances 0.000 description 8
- 238000000926 separation method Methods 0.000 description 8
- VEEYIEPLTXTQLZ-UHFFFAOYSA-N 5-oxopyrrolo[3,2-e]indole-3-carboxylic acid Chemical compound C1=CN=C2C1=C3C=CN(C3=CC2=O)C(=O)O VEEYIEPLTXTQLZ-UHFFFAOYSA-N 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 238000010511 deprotection reaction Methods 0.000 description 7
- QKGYJVXSKCDGOK-UHFFFAOYSA-N hexane;propan-2-ol Chemical compound CC(C)O.CCCCCC QKGYJVXSKCDGOK-UHFFFAOYSA-N 0.000 description 7
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- XOLBXXZZQLVKRU-UHFFFAOYSA-N C1CC1.[C] Chemical class C1CC1.[C] XOLBXXZZQLVKRU-UHFFFAOYSA-N 0.000 description 6
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 150000001336 alkenes Chemical class 0.000 description 6
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- QKSIOTOKHGNPNU-UHFFFAOYSA-N 4-oxoindole-6-carboxylic acid Chemical compound OC(=O)C1=CC(=O)C2=CC=NC2=C1 QKSIOTOKHGNPNU-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- AZVARJHZBXHUSO-UHFFFAOYSA-N Duocarmycin A Natural products COC1=C(OC)C(OC)=C2NC(C(=O)N3CC4CC44C5=C(C(C=C43)=O)NC(C5=O)(C)C(=O)OC)=CC2=C1 AZVARJHZBXHUSO-UHFFFAOYSA-N 0.000 description 5
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- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 5
- 150000004702 methyl esters Chemical class 0.000 description 5
- CZFNISFYDPIDNM-UHFFFAOYSA-N n,n-dimethylformamide;oxolane Chemical compound CN(C)C=O.C1CCOC1 CZFNISFYDPIDNM-UHFFFAOYSA-N 0.000 description 5
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- 238000012163 sequencing technique Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000012192 staining solution Substances 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- CNMDREPWSZVYGL-UHFFFAOYSA-N tert-butyl n-(1-iodo-4-phenylmethoxynaphthalen-2-yl)carbamate Chemical group C=12C=CC=CC2=C(I)C(NC(=O)OC(C)(C)C)=CC=1OCC1=CC=CC=C1 CNMDREPWSZVYGL-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000009452 underexpressoin Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/32—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems containing carbocyclic rings other than six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D225/00—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom
- C07D225/04—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Compounds Of Unknown Constitution (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US4850597P | 1997-05-22 | 1997-05-22 | |
| US60/048,505 | 1997-05-22 | ||
| PCT/US1998/010535 WO1998052925A1 (en) | 1997-05-22 | 1998-05-22 | Analogs of duocarmycin and cc-1065 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002503228A true JP2002503228A (ja) | 2002-01-29 |
| JP2002503228A5 JP2002503228A5 (enExample) | 2005-12-08 |
Family
ID=21954939
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP55069798A Ceased JP2002503228A (ja) | 1997-05-22 | 1998-05-22 | デュオカルマイシンおよびｃｃ−１０６５の類似体 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US6281354B1 (enExample) |
| EP (1) | EP0983248B1 (enExample) |
| JP (1) | JP2002503228A (enExample) |
| AT (1) | ATE271041T1 (enExample) |
| AU (1) | AU754083B2 (enExample) |
| CA (1) | CA2290789A1 (enExample) |
| DE (1) | DE69825048D1 (enExample) |
| NZ (1) | NZ500789A (enExample) |
| WO (1) | WO1998052925A1 (enExample) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE378328T1 (de) * | 2001-02-22 | 2007-11-15 | Univ London Pharmacy | Pyrrolo-indol- und pyrrolo-chinolin-derivate als prodrugs zur tumorbehandlung |
| PT1392359E (pt) | 2001-05-11 | 2010-01-27 | Ludwig Inst For Cancer Res Ltd | Proteínas de ligação específica e suas utilizações |
| US20100056762A1 (en) | 2001-05-11 | 2010-03-04 | Old Lloyd J | Specific binding proteins and uses thereof |
| US6989452B2 (en) | 2001-05-31 | 2006-01-24 | Medarex, Inc. | Disulfide prodrugs and linkers and stabilizers useful therefor |
| DE10147672A1 (de) * | 2001-09-27 | 2003-04-10 | Bayer Ag | Substituierte 2,5-Diamidoindole und ihre Verwendung |
| EP1554271A1 (en) * | 2002-10-15 | 2005-07-20 | Rigel Pharmaceuticals, Inc. | Substituted indoles and their use as hcv inhibitors |
| US20060167271A1 (en) * | 2002-11-14 | 2006-07-27 | Mark Ginsberg | Purified compounds that inhibit intracellular alphax4/paxillin binding |
| AU2005221959C1 (en) * | 2004-03-13 | 2010-06-17 | Kyoto University | Novel indole derivative for alkylating specific base sequence of DNA and alkylating agent and drug each comprising the same |
| RU2402548C2 (ru) * | 2004-05-19 | 2010-10-27 | Медарекс, Инк. | Химические линкеры и их конъюгаты |
| MXPA06013413A (es) | 2004-05-19 | 2007-01-23 | Medarex Inc | Enlazadores quimicos y conjugados de los mismos. |
| US7714016B2 (en) * | 2005-04-08 | 2010-05-11 | Medarex, Inc. | Cytotoxic compounds and conjugates with cleavable substrates |
| JP5290756B2 (ja) * | 2005-09-26 | 2013-09-18 | メダレックス インコーポレイテッド | 抗体−薬剤コンジュゲート及びその使用 |
| CA2623236A1 (en) | 2005-09-26 | 2007-04-05 | Medarex, Inc. | Human monoclonal antibodies to cd70 |
| EP1940789B1 (en) | 2005-10-26 | 2011-11-23 | Medarex, Inc. | Methods and compounds for preparing cc-1065 analogs |
| WO2007059404A2 (en) | 2005-11-10 | 2007-05-24 | Medarex, Inc. | Duocarmycin derivatives as novel cytotoxic compounds and conjugates |
| WO2007067992A2 (en) | 2005-12-08 | 2007-06-14 | Medarex, Inc. | Human monoclonal antibodies to fucosyl-gm1 and methods for using anti-fucosyl-gm1 |
| EA017812B1 (ru) | 2005-12-08 | 2013-03-29 | Медарекс, Инк. | Выделенное моноклональное антитело или его антигенсвязывающий участок, которые связываются с протеинтирозинкиназой 7 ( ptk7) человека, и их применение |
| ES2396569T3 (es) | 2006-01-17 | 2013-02-22 | Medarex, Inc. | Anticuerpos monoclonales contra CD30 que carecen de restos fucosilo y xilosilo |
| WO2008030611A2 (en) | 2006-09-05 | 2008-03-13 | Medarex, Inc. | Antibodies to bone morphogenic proteins and receptors therefor and methods for their use |
| CN103172743B (zh) | 2006-12-01 | 2015-04-08 | 梅达雷克斯有限责任公司 | 结合cd22的人抗体及其用途 |
| CL2007003622A1 (es) | 2006-12-13 | 2009-08-07 | Medarex Inc | Anticuerpo monoclonal humano anti-cd19; composicion que lo comprende; y metodo de inhibicion del crecimiento de celulas tumorales. |
| US20100150950A1 (en) | 2006-12-14 | 2010-06-17 | Medarex, Inc. | Human antibodies that bind cd70 and uses thereof |
| TWI412367B (zh) | 2006-12-28 | 2013-10-21 | Medarex Llc | 化學鏈接劑與可裂解基質以及其之綴合物 |
| WO2008091701A2 (en) | 2007-01-25 | 2008-07-31 | Dana-Farber Cancer Institute | Use of anti-egfr antibodies in treatment of egfr mutant mediated disease |
| JP2010519310A (ja) | 2007-02-21 | 2010-06-03 | メダレックス インコーポレイテッド | 単一のアミノ酸を有する化学リンカーおよびその複合体 |
| CA2680854C (en) | 2007-03-15 | 2017-02-14 | Ludwig Institute For Cancer Research | Treatment method using egfr antibodies and src inhibitors and related formulations |
| US9901567B2 (en) | 2007-08-01 | 2018-02-27 | Syntarga B.V. | Substituted CC-1065 analogs and their conjugates |
| MX2010001757A (es) | 2007-08-14 | 2010-09-14 | Ludwig Inst Cancer Res | Anticuerpo monoclonal 175 que activa el receptor egf y derivados y usos del mismo. |
| AU2009320481C1 (en) | 2008-11-03 | 2016-12-08 | Syntarga B.V. | Novel CC-1065 analogs and their conjugates |
| BRPI1009232B1 (pt) | 2009-03-05 | 2022-05-03 | E.R. Squibb & Sons, Llc. | Anticorpo monoclonal isolado ou uma porção de ligação de antígeno do mesmo, ou um fragmento de anticorpo, composição que os compreende, molécula de ácido nucleico, hibridoma e métodos para a preparação de um anticorpo anti-cadm1 |
| US9181339B2 (en) | 2009-04-20 | 2015-11-10 | Oxford Bio Therapeutics Ltd. | Antibodies specific to cadherin-17 |
| US20120231004A1 (en) | 2009-10-13 | 2012-09-13 | Oxford Biotherapeutic Ltd. | Antibodies |
| US9173961B2 (en) | 2010-02-10 | 2015-11-03 | Immunogen, Inc. | CD20 antibodies and uses thereof |
| PT3056203T (pt) | 2010-04-21 | 2018-02-15 | Syntarga Bv | Conjugados de análogos de cc-1065 e ligantes bifuncionais |
| PL2726508T3 (pl) | 2011-06-28 | 2017-12-29 | Oxford Biotherapeutics Ltd | Przeciwciała przeciwko cyklazie ADP-rybozylowej 2 |
| EP2922818B1 (en) | 2012-11-24 | 2018-09-05 | Hangzhou Dac Biotech Co., Ltd | Hydrophilic linkers and their uses for conjugation of drugs to cell binding molecules |
| US9089614B2 (en) | 2012-12-21 | 2015-07-28 | Bioalliance C.V. | Hydrophilic self-immolative linkers and conjugates thereof |
| WO2015050959A1 (en) | 2013-10-01 | 2015-04-09 | Yale University | Anti-kit antibodies and methods of use thereof |
| EP3092010B1 (en) | 2014-01-10 | 2018-07-11 | Synthon Biopharmaceuticals B.V. | Method for purifying cys-linked antibody-drug conjugates |
| AU2014384434B2 (en) | 2014-02-28 | 2016-11-03 | Hangzhou Dac Biotech Co., Ltd | Charged linkers and their uses for conjugation |
| JP2017528418A (ja) | 2014-06-20 | 2017-09-28 | バイオアライアンス コマンディテール フェンノートシャップ | 抗葉酸受容体アルファ（ｆｒａ）抗体−薬物コンジュゲート及びその使用方法 |
| NZ739830A (en) | 2015-07-12 | 2021-12-24 | Hangzhou Dac Biotech Co Ltd | Bridge linkers for conjugation of cell-binding molecules |
| US9839687B2 (en) | 2015-07-15 | 2017-12-12 | Suzhou M-Conj Biotech Co., Ltd. | Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule |
| ES2880731T3 (es) | 2016-01-08 | 2021-11-25 | Altrubio Inc | Anticuerpos anti-PSGL-1 tetravalentes y usos de los mismos |
| KR102493853B1 (ko) | 2016-08-19 | 2023-01-30 | 브리스톨-마이어스 스큅 컴퍼니 | 세코-시클로프로파피롤로인돌 화합물, 그의 항체-약물 접합체, 및 제조 및 사용 방법 |
| WO2018064094A1 (en) | 2016-09-28 | 2018-04-05 | Bristol-Myers Squibb Company | Enantioselective synthesis of pyrroloindole compounds |
| KR102345175B1 (ko) | 2016-11-14 | 2021-12-31 | 항저우 디에이씨 바이오테크 씨오, 엘티디 | 결합 링커, 그러한 결합 링커를 함유하는 세포 결합 분자-약물 결합체, 링커를 갖는 그러한 결합체의 제조 및 사용 |
| CA3236930A1 (en) | 2021-11-03 | 2022-04-21 | Hangzhou Dac Biotech Co., Ltd. | Specific conjugation of an antibody |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1238907A (en) * | 1984-02-21 | 1988-07-05 | Robert C. Kelly | 1,2,8,8a-tetrahydrocyclopropa¬c|pyrrolo(3,2-e)- indol-4(5h)-ones and related compounds |
| US5084468A (en) * | 1988-08-11 | 1992-01-28 | Kyowa Hakko Kogyo Co., Ltd. | Dc-88a derivatives |
| US5008271A (en) * | 1988-10-21 | 1991-04-16 | Kyowa Hakko Kogyo Co., Ltd. | DC-88A derivatives |
| US5214065A (en) * | 1990-06-11 | 1993-05-25 | Kyowa Hakko Kogyo Co., Ltd. | Dc-89 derivatives |
| US6060608A (en) * | 1996-05-31 | 2000-05-09 | The Scripps Research Institute | Analogs of CC-1065 and the duocarmycins |
-
1998
- 1998-05-22 CA CA002290789A patent/CA2290789A1/en not_active Abandoned
- 1998-05-22 AT AT98924851T patent/ATE271041T1/de not_active IP Right Cessation
- 1998-05-22 WO PCT/US1998/010535 patent/WO1998052925A1/en not_active Ceased
- 1998-05-22 DE DE69825048T patent/DE69825048D1/de not_active Expired - Lifetime
- 1998-05-22 AU AU76927/98A patent/AU754083B2/en not_active Ceased
- 1998-05-22 EP EP98924851A patent/EP0983248B1/en not_active Expired - Lifetime
- 1998-05-22 NZ NZ500789A patent/NZ500789A/en unknown
- 1998-05-22 JP JP55069798A patent/JP2002503228A/ja not_active Ceased
-
1999
- 1999-11-09 US US09/423,576 patent/US6281354B1/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP0983248A1 (en) | 2000-03-08 |
| AU754083B2 (en) | 2002-11-07 |
| NZ500789A (en) | 2002-05-31 |
| US6281354B1 (en) | 2001-08-28 |
| EP0983248A4 (en) | 2000-09-13 |
| AU7692798A (en) | 1998-12-11 |
| ATE271041T1 (de) | 2004-07-15 |
| CA2290789A1 (en) | 1998-11-26 |
| EP0983248B1 (en) | 2004-07-14 |
| DE69825048D1 (de) | 2004-08-19 |
| WO1998052925A1 (en) | 1998-11-26 |
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