CA2290789A1 - Analogs of duocarmycin and cc-1065 - Google Patents
Analogs of duocarmycin and cc-1065 Download PDFInfo
- Publication number
- CA2290789A1 CA2290789A1 CA002290789A CA2290789A CA2290789A1 CA 2290789 A1 CA2290789 A1 CA 2290789A1 CA 002290789 A CA002290789 A CA 002290789A CA 2290789 A CA2290789 A CA 2290789A CA 2290789 A1 CA2290789 A1 CA 2290789A1
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- Prior art keywords
- alkylation
- dna
- equiv
- ring
- 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.)
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- 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 claims abstract description 53
- 229960005501 duocarmycin Drugs 0.000 title description 8
- 229930184221 duocarmycin Natural products 0.000 title description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 59
- 229960005532 CC-1065 Drugs 0.000 claims abstract description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 101
- -1 N-substituted pyrrolidine ring Chemical group 0.000 claims description 63
- 125000000217 alkyl group Chemical group 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 17
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 15
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 12
- 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 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical class C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 abstract description 159
- 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 abstract description 16
- 230000002152 alkylating effect Effects 0.000 abstract description 8
- 239000003242 anti bacterial agent Substances 0.000 abstract description 5
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- 229940088710 antibiotic agent Drugs 0.000 abstract description 5
- 230000007541 cellular toxicity Effects 0.000 abstract 1
- 238000005804 alkylation reaction Methods 0.000 description 187
- 230000029936 alkylation Effects 0.000 description 159
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- 238000005481 NMR spectroscopy Methods 0.000 description 99
- 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 76
- 150000001408 amides Chemical class 0.000 description 75
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 62
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- GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical group N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 58
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 42
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 41
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 32
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- 239000000047 product Substances 0.000 description 27
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- 101150041968 CDC13 gene Proteins 0.000 description 24
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- 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 24
- 229960005510 duocarmycin SA Drugs 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
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- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 18
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- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 15
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 15
- 230000004913 activation Effects 0.000 description 15
- AYYOZKHMSABVRP-UHFFFAOYSA-N methyl 1h-indole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C=CNC2=C1 AYYOZKHMSABVRP-UHFFFAOYSA-N 0.000 description 15
- PUPKPAZSFZOLOR-UHFFFAOYSA-N n,n-dimethylformamide;toluene Chemical compound CN(C)C=O.CC1=CC=CC=C1 PUPKPAZSFZOLOR-UHFFFAOYSA-N 0.000 description 15
- 238000006265 spirocyclization reaction Methods 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
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- XOLBXXZZQLVKRU-UHFFFAOYSA-N C1CC1.[C] Chemical compound C1CC1.[C] XOLBXXZZQLVKRU-UHFFFAOYSA-N 0.000 description 10
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- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 10
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
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- QKGYJVXSKCDGOK-UHFFFAOYSA-N hexane;propan-2-ol Chemical compound CC(C)O.CCCCCC QKGYJVXSKCDGOK-UHFFFAOYSA-N 0.000 description 8
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- 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 6
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- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
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- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 238000006197 hydroboration reaction Methods 0.000 description 1
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- DCPMPXBYPZGNDC-UHFFFAOYSA-N hydron;methanediimine;chloride Chemical compound Cl.N=C=N DCPMPXBYPZGNDC-UHFFFAOYSA-N 0.000 description 1
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- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
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- 238000012423 maintenance Methods 0.000 description 1
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- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 238000006140 methanolysis reaction Methods 0.000 description 1
- KRPDKDKJKIBCBX-UHFFFAOYSA-N methyl 5-amino-1h-indole-2-carboxylate Chemical compound NC1=CC=C2NC(C(=O)OC)=CC2=C1 KRPDKDKJKIBCBX-UHFFFAOYSA-N 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 1
- ZIUHHBKFKCYYJD-UHFFFAOYSA-N n,n'-methylenebisacrylamide Chemical compound C=CC(=O)NCNC(=O)C=C ZIUHHBKFKCYYJD-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- XOOMNEFVDUTJPP-UHFFFAOYSA-N naphthalene-1,3-diol Chemical compound C1=CC=CC2=CC(O)=CC(O)=C21 XOOMNEFVDUTJPP-UHFFFAOYSA-N 0.000 description 1
- SNLLCSDUARMKPB-UHFFFAOYSA-M oxan-2-yloxymethyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)COC1CCCCO1 SNLLCSDUARMKPB-UHFFFAOYSA-M 0.000 description 1
- SMPAPEKFGLKOIC-UHFFFAOYSA-N oxolane;hydrochloride Chemical compound Cl.C1CCOC1 SMPAPEKFGLKOIC-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-O oxonium Chemical compound [OH3+] XLYOFNOQVPJJNP-UHFFFAOYSA-O 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- OFTHSKYOGOJVQF-UHFFFAOYSA-N pent-4-enyl methanesulfonate Chemical compound CS(=O)(=O)OCCCC=C OFTHSKYOGOJVQF-UHFFFAOYSA-N 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- YLZWEPNHBVOIBC-UHFFFAOYSA-N pyrrolo[3,2-e]indole Chemical compound C1=CC2=NC=CC2=C2C=CN=C21 YLZWEPNHBVOIBC-UHFFFAOYSA-N 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- IQEHMNCMUZFAHU-UHFFFAOYSA-N tert-butyl 1-(chloromethyl)-7-hydroxy-2,3,4,5-tetrahydrobenzo[i][1]benzazepine-5-carboxylate Chemical compound CC(C)(C)OC(=O)C1CCCN(CCl)C2=C1C=C(O)C1=CC=CC=C21 IQEHMNCMUZFAHU-UHFFFAOYSA-N 0.000 description 1
- PQCCFAGWRSTQPM-UHFFFAOYSA-N tert-butyl 1-(chloromethyl)-7-phenylmethoxy-2,3,4,5-tetrahydrobenzo[i][1]benzazepine-5-carboxylate Chemical compound CC(C)(C)OC(=O)C1CCCN(CCl)C(C2=CC=CC=C22)=C1C=C2OCC1=CC=CC=C1 PQCCFAGWRSTQPM-UHFFFAOYSA-N 0.000 description 1
- FKCGINOGVPKVRC-UHFFFAOYSA-N tert-butyl n-(1-iodo-4-phenylmethoxynaphthalen-2-yl)-n-(4-oxobutyl)carbamate Chemical compound C=12C=CC=CC2=C(I)C(N(CCCC=O)C(=O)OC(C)(C)C)=CC=1OCC1=CC=CC=C1 FKCGINOGVPKVRC-UHFFFAOYSA-N 0.000 description 1
- WRPUZHVCRAQLDF-UHFFFAOYSA-N tert-butyl n-(1-iodo-4-phenylmethoxynaphthalen-2-yl)-n-[5-(oxan-2-yloxy)pent-4-enyl]carbamate Chemical compound C=1C(OCC=2C=CC=CC=2)=C2C=CC=CC2=C(I)C=1N(C(=O)OC(C)(C)C)CCCC=COC1CCCCO1 WRPUZHVCRAQLDF-UHFFFAOYSA-N 0.000 description 1
- FLNTWIAGHYVPKR-UHFFFAOYSA-N tert-butyl n-(1-iodo-4-phenylmethoxynaphthalen-2-yl)-n-pent-4-enylcarbamate Chemical compound C=12C=CC=CC2=C(I)C(N(CCCC=C)C(=O)OC(C)(C)C)=CC=1OCC1=CC=CC=C1 FLNTWIAGHYVPKR-UHFFFAOYSA-N 0.000 description 1
- CNMDREPWSZVYGL-UHFFFAOYSA-N tert-butyl n-(1-iodo-4-phenylmethoxynaphthalen-2-yl)carbamate Chemical compound 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
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- 238000001149 thermolysis Methods 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000003260 vortexing Methods 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)
- Plural Heterocyclic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (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 (1)
| Publication Number | Publication Date |
|---|---|
| CA2290789A1 true CA2290789A1 (en) | 1998-11-26 |
Family
ID=21954939
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002290789A Abandoned CA2290789A1 (en) | 1997-05-22 | 1998-05-22 | Analogs of duocarmycin and cc-1065 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US6281354B1 (https=) |
| EP (1) | EP0983248B1 (https=) |
| JP (1) | JP2002503228A (https=) |
| AT (1) | ATE271041T1 (https=) |
| AU (1) | AU754083B2 (https=) |
| CA (1) | CA2290789A1 (https=) |
| DE (1) | DE69825048D1 (https=) |
| NZ (1) | NZ500789A (https=) |
| WO (1) | WO1998052925A1 (https=) |
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| ES2299560T3 (es) | 2001-02-22 | 2008-06-01 | University Of Bradford | Derivados de pirrolindol y de pirroloquinolina como profarmacos para el tratamiento de tumores. |
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| 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 |
| WO2004035571A1 (en) * | 2002-10-15 | 2004-04-29 | Rigel Pharmaceuticals, Inc. | Substituted indoles and their use as hcv inhibitors |
| WO2004043350A2 (en) * | 2002-11-14 | 2004-05-27 | The Scripps Research Institute | PURIFIED COMPOUNDS THAT INHIBIT INTRACELLULAR α4/PAXILLIN BINDING |
| CN100519555C (zh) * | 2004-03-13 | 2009-07-29 | Tmrc株式会社 | 将dna的特定碱基序列烷基化的新吲哚衍生物和使用其的烷基化剂以及药剂 |
| US7691962B2 (en) * | 2004-05-19 | 2010-04-06 | Medarex, Inc. | Chemical linkers and conjugates thereof |
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| US7714016B2 (en) * | 2005-04-08 | 2010-05-11 | Medarex, Inc. | Cytotoxic compounds and conjugates with cleavable substrates |
| NZ566395A (en) | 2005-09-26 | 2012-03-30 | Medarex Inc | Human monoclonal antibodies to CD70 |
| EP2354163A3 (en) * | 2005-09-26 | 2013-04-24 | Medarex, Inc. | Conjugates of duocarmycin and anti-CD70 or anti-PSMA antibodies |
| RS52100B (sr) | 2005-10-26 | 2012-06-30 | Medarex, Inc. | Postupci i jedinjenja za pripremu analoga cc-1065 |
| WO2007059404A2 (en) | 2005-11-10 | 2007-05-24 | Medarex, Inc. | Duocarmycin derivatives as novel cytotoxic compounds and conjugates |
| US8383118B2 (en) | 2005-12-08 | 2013-02-26 | 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 |
| US20090175886A1 (en) | 2006-01-17 | 2009-07-09 | Medarex, Inc. | Monoclonal antibodies against cd30 lacking in fucosyl and xylosyl residues |
| CA2662350A1 (en) | 2006-09-05 | 2008-03-13 | Medarex, Inc. | Antibodies to bone morphogenic proteins and receptors therefor and methods for their use |
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| MX2009006277A (es) | 2006-12-14 | 2009-07-24 | Medarex Inc | Anticuerpos humanos que se enlazan a cd70 y usos de los mismos. |
| TWI412367B (zh) | 2006-12-28 | 2013-10-21 | 梅達雷克斯有限責任公司 | 化學鏈接劑與可裂解基質以及其之綴合物 |
| US9090693B2 (en) | 2007-01-25 | 2015-07-28 | Dana-Farber Cancer Institute | Use of anti-EGFR antibodies in treatment of EGFR mutant mediated disease |
| AR065404A1 (es) | 2007-02-21 | 2009-06-03 | Medarex Inc | Conjugados farmaco-ligando, los que se unen a citotoxinas potentes, composicion farmaceutica que los contienen y su uso para retardar o detener el crecimiento de un tumor en un mamifero |
| 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 |
| CN108424454B (zh) | 2007-08-14 | 2022-05-31 | 路德维格癌症研究所有限公司 | 靶向egf受体的单克隆抗体175及其衍生物和用途 |
| ES2647317T3 (es) | 2008-11-03 | 2017-12-20 | Syntarga B.V. | Análogos de CC-1065 y sus conjugados |
| CN102341412B (zh) | 2009-03-05 | 2018-01-05 | 梅达雷克斯有限责任公司 | 特异于cadm1 的全人抗体 |
| DK2421898T3 (en) | 2009-04-20 | 2016-05-30 | Oxford Biotherapeutics Ltd | Cadherin-17 SPECIFIC ANTIBODIES |
| EP2470569A1 (en) | 2009-10-13 | 2012-07-04 | Oxford Biotherapeutics Ltd. | Antibodies against epha10 |
| KR20130009760A (ko) | 2010-02-10 | 2013-01-23 | 이뮤노젠 아이엔씨 | Ｃｄ２０ 항체 및 이의 용도 |
| 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 |
| CA2891280C (en) | 2012-11-24 | 2018-03-20 | 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 |
| RU2680404C2 (ru) | 2014-01-10 | 2019-02-21 | Синтон Байофармасьютикалс Б. В. | Способ очистки cys-связанных конъюгатов антитело-лекарственное средство |
| US10464955B2 (en) | 2014-02-28 | 2019-11-05 | Hangzhou Dac Biotech Co., Ltd. | Charged linkers and their uses for conjugation |
| US9950077B2 (en) | 2014-06-20 | 2018-04-24 | Bioalliance C.V. | Anti-folate receptor alpha (FRA) antibody-drug conjugates and methods of using thereof |
| 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 |
| IL260289B (en) | 2016-01-08 | 2022-08-01 | Bioalliance Cv | Tetravalent anti-psgl-1 antibodies and uses thereof |
| CN109641911B (zh) | 2016-08-19 | 2023-02-21 | 百时美施贵宝公司 | seco-环丙吡咯并吲哚化合物和其抗体-药物缀合物以及制备和使用方法 |
| WO2018064094A1 (en) | 2016-09-28 | 2018-04-05 | Bristol-Myers Squibb Company | Enantioselective synthesis of pyrroloindole compounds |
| KR20220150408A (ko) | 2016-11-14 | 2022-11-10 | 항저우 디에이씨 바이오테크 씨오, 엘티디 | 결합 링커, 그러한 결합 링커를 함유하는 세포 결합 분자-약물 결합체, 링커를 갖는 그러한 결합체의 제조 및 사용 |
| EP4426727A2 (en) | 2021-11-03 | 2024-09-11 | 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 |
| EP0934269A4 (en) * | 1996-05-31 | 2000-01-12 | Scripps Research Inst | ANALOGS OF CC-1065 AND DUOCARMYCINE |
-
1998
- 1998-05-22 NZ NZ500789A patent/NZ500789A/en unknown
- 1998-05-22 EP EP98924851A patent/EP0983248B1/en not_active Expired - Lifetime
- 1998-05-22 AT AT98924851T patent/ATE271041T1/de not_active IP Right Cessation
- 1998-05-22 CA CA002290789A patent/CA2290789A1/en not_active Abandoned
- 1998-05-22 AU AU76927/98A patent/AU754083B2/en not_active Ceased
- 1998-05-22 DE DE69825048T patent/DE69825048D1/de not_active Expired - Lifetime
- 1998-05-22 JP JP55069798A patent/JP2002503228A/ja not_active Ceased
- 1998-05-22 WO PCT/US1998/010535 patent/WO1998052925A1/en 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 |
|---|---|
| EP0983248B1 (en) | 2004-07-14 |
| EP0983248A1 (en) | 2000-03-08 |
| AU7692798A (en) | 1998-12-11 |
| EP0983248A4 (en) | 2000-09-13 |
| ATE271041T1 (de) | 2004-07-15 |
| DE69825048D1 (de) | 2004-08-19 |
| WO1998052925A1 (en) | 1998-11-26 |
| AU754083B2 (en) | 2002-11-07 |
| JP2002503228A (ja) | 2002-01-29 |
| NZ500789A (en) | 2002-05-31 |
| US6281354B1 (en) | 2001-08-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |