NO317670B1 - Nye Dolastatinderivater, deres fremstilling og anvendelse - Google Patents
Nye Dolastatinderivater, deres fremstilling og anvendelse Download PDFInfo
- Publication number
- NO317670B1 NO317670B1 NO19975711A NO975711A NO317670B1 NO 317670 B1 NO317670 B1 NO 317670B1 NO 19975711 A NO19975711 A NO 19975711A NO 975711 A NO975711 A NO 975711A NO 317670 B1 NO317670 B1 NO 317670B1
- Authority
- NO
- Norway
- Prior art keywords
- xaa val
- methyl
- val xab
- tert
- acid
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title abstract description 4
- AMRJKAQTDDKMCE-UHFFFAOYSA-N dolastatin Chemical class CC(C)C(N(C)C)C(=O)NC(C(C)C)C(=O)N(C)C(C(C)C)C(OC)CC(=O)N1CCCC1C(OC)C(C)C(=O)NC(C=1SC=CN=1)CC1=CC=CC=C1 AMRJKAQTDDKMCE-UHFFFAOYSA-N 0.000 title abstract description 3
- -1 2-tert-butylflycyl Chemical group 0.000 claims description 79
- 150000001875 compounds Chemical class 0.000 claims description 31
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 29
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 206010028980 Neoplasm Diseases 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000000741 isoleucyl group Chemical group [H]N([H])C(C(C([H])([H])[H])C([H])([H])C([H])([H])[H])C(=O)O* 0.000 claims description 6
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 229950003188 isovaleryl diethylamide Drugs 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 4
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 230000000771 oncological effect Effects 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 3
- 125000002114 valyl group Chemical group 0.000 claims 2
- 125000001980 alanyl group Chemical group 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 5
- 230000000118 anti-neoplastic effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- 239000011347 resin Substances 0.000 description 25
- 229920005989 resin Polymers 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 229940024606 amino acid Drugs 0.000 description 13
- 150000001413 amino acids Chemical class 0.000 description 13
- 239000000243 solution Substances 0.000 description 12
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 230000008878 coupling Effects 0.000 description 8
- 238000010168 coupling process Methods 0.000 description 8
- 238000005859 coupling reaction Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000003776 cleavage reaction Methods 0.000 description 7
- 239000012634 fragment Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 150000002431 hydrogen Chemical group 0.000 description 6
- 238000010647 peptide synthesis reaction Methods 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 5
- 235000015165 citric acid Nutrition 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 3
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 3
- LQKSHSFQQRCAFW-UHFFFAOYSA-N Dolastatin 15 Natural products COC1=CC(=O)N(C(=O)C(OC(=O)C2N(CCC2)C(=O)C2N(CCC2)C(=O)C(C(C)C)N(C)C(=O)C(NC(=O)C(C(C)C)N(C)C)C(C)C)C(C)C)C1CC1=CC=CC=C1 LQKSHSFQQRCAFW-UHFFFAOYSA-N 0.000 description 3
- 230000005526 G1 to G0 transition Effects 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- AKCRVYNORCOYQT-YFKPBYRVSA-N N-methyl-L-valine Chemical compound CN[C@@H](C(C)C)C(O)=O AKCRVYNORCOYQT-YFKPBYRVSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- LQKSHSFQQRCAFW-CCVNJFHASA-N [(2s)-1-[(2s)-2-benzyl-3-methoxy-5-oxo-2h-pyrrol-1-yl]-3-methyl-1-oxobutan-2-yl] (2s)-1-[(2s)-1-[(2s)-2-[[(2s)-2-[[(2s)-2-(dimethylamino)-3-methylbutanoyl]amino]-3-methylbutanoyl]-methylamino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carboxyl Chemical compound C([C@@H]1N(C(=O)C=C1OC)C(=O)[C@@H](OC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H](C(C)C)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C)C(C)C)C(C)C)C1=CC=CC=C1 LQKSHSFQQRCAFW-CCVNJFHASA-N 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
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- VLNZUSMTOFYNPS-UHFFFAOYSA-N diethylphosphorylformonitrile Chemical compound CCP(=O)(CC)C#N VLNZUSMTOFYNPS-UHFFFAOYSA-N 0.000 description 3
- 108010045552 dolastatin 15 Proteins 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
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- 239000006260 foam Substances 0.000 description 3
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- 238000001727 in vivo Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
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- 239000012071 phase Substances 0.000 description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
- 238000005932 reductive alkylation reaction Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- GNZSGDFUKQDBQB-ZAGFBCOMSA-N (2S,3S)-3-methyl-N-[[1-[(2S)-pyrrolidine-2-carbonyl]cyclohexa-2,4-dien-1-yl]methyl]pyrrolidine-2-carboxamide Chemical compound C[C@H]1CCN[C@@H]1C(=O)NCC2(CC=CC=C2)C(=O)[C@@H]3CCCN3 GNZSGDFUKQDBQB-ZAGFBCOMSA-N 0.000 description 2
- UGNIYGNGCNXHTR-SFHVURJKSA-N (2s)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@@H](C(C)C)C(O)=O)C3=CC=CC=C3C2=C1 UGNIYGNGCNXHTR-SFHVURJKSA-N 0.000 description 2
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 2
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- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
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- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
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- 102000007079 Peptide Fragments Human genes 0.000 description 2
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- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
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- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 2
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- SZNKRADUZXAHCO-MERQFXBCSA-N (2s)-n-benzylpyrrolidine-2-carboxamide;hydrochloride Chemical compound Cl.O=C([C@H]1NCCC1)NCC1=CC=CC=C1 SZNKRADUZXAHCO-MERQFXBCSA-N 0.000 description 1
- CNPSFBUUYIVHAP-WHFBIAKZSA-N (2s,3s)-3-methylpyrrolidin-1-ium-2-carboxylate Chemical compound C[C@H]1CCN[C@@H]1C(O)=O CNPSFBUUYIVHAP-WHFBIAKZSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1005—Tetrapeptides with the first amino acid being neutral and aliphatic
- C07K5/101—Tetrapeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/472,453 US5831002A (en) | 1992-05-20 | 1995-06-07 | Antitumor peptides |
| PCT/EP1996/002392 WO1996040751A1 (en) | 1995-06-07 | 1996-06-03 | Novel dolastatin derivatives, their preparation and use |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO975711D0 NO975711D0 (no) | 1997-12-05 |
| NO975711L NO975711L (no) | 1998-01-30 |
| NO317670B1 true NO317670B1 (no) | 2004-11-29 |
Family
ID=23875567
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19975710A NO318384B1 (no) | 1995-06-07 | 1997-12-05 | Nye Dolastatinderivater, deres fremstilling og anvendelse, samt farmasoytiske blandinger inneholdende disse. |
| NO19975711A NO317670B1 (no) | 1995-06-07 | 1997-12-05 | Nye Dolastatinderivater, deres fremstilling og anvendelse |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19975710A NO318384B1 (no) | 1995-06-07 | 1997-12-05 | Nye Dolastatinderivater, deres fremstilling og anvendelse, samt farmasoytiske blandinger inneholdende disse. |
Country Status (33)
| Country | Link |
|---|---|
| US (1) | US5831002A (ko) |
| EP (2) | EP0871656B1 (ko) |
| JP (2) | JP4221062B2 (ko) |
| KR (2) | KR100437985B1 (ko) |
| CN (2) | CN1182154C (ko) |
| AR (2) | AR003427A1 (ko) |
| AT (2) | ATE224910T1 (ko) |
| AU (2) | AU725164B2 (ko) |
| BG (2) | BG102125A (ko) |
| BR (2) | BR9609423A (ko) |
| CA (2) | CA2219818C (ko) |
| CO (2) | CO4700527A1 (ko) |
| CZ (2) | CZ293682B6 (ko) |
| DE (2) | DE69623992T2 (ko) |
| DK (2) | DK0871656T3 (ko) |
| ES (2) | ES2186783T3 (ko) |
| HR (2) | HRP960277A2 (ko) |
| HU (2) | HU228073B1 (ko) |
| IL (2) | IL122216A (ko) |
| MX (2) | MX9709146A (ko) |
| MY (2) | MY119042A (ko) |
| NO (2) | NO318384B1 (ko) |
| NZ (2) | NZ310443A (ko) |
| PL (2) | PL185762B1 (ko) |
| PT (2) | PT832104E (ko) |
| RO (2) | RO119783B1 (ko) |
| SI (2) | SI0832104T1 (ko) |
| SK (1) | SK282466B6 (ko) |
| TR (2) | TR199701544T1 (ko) |
| TW (2) | TW508357B (ko) |
| UA (2) | UA46775C2 (ko) |
| WO (2) | WO1996040752A1 (ko) |
| ZA (2) | ZA964710B (ko) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5807984A (en) * | 1995-11-09 | 1998-09-15 | Basf Aktienegesellschaft | Oligopeptides, the preparation and use thereof |
| TW474946B (en) * | 1995-12-15 | 2002-02-01 | Basf Ag | Novel compounds, the preparation and use thereof |
| US20010009901A1 (en) * | 1996-12-11 | 2001-07-26 | Basf Aktiengesellschaft Germany | Antineoplastic peptides |
| US5965537A (en) * | 1997-03-10 | 1999-10-12 | Basf Aktiengesellschaft | Dolastatin 15 derivatives with carbonyl and heterocyclic functionalities at the C-terminus |
| US6103698A (en) * | 1997-03-13 | 2000-08-15 | Basf Aktiengesellschaft | Dolastatin-15 derivatives in combination with taxanes |
| US6143721A (en) * | 1997-07-18 | 2000-11-07 | Basf Aktiengesellschaft | Dolastatin 15 derivatives |
| US6015790A (en) * | 1997-10-06 | 2000-01-18 | Basf Aktiengesellschaft | Methods and compositions for treating rheumatoid arthritis |
| US5985837A (en) * | 1998-07-08 | 1999-11-16 | Basf Aktiengesellschaft | Dolastatin 15 derivatives |
| JP2002538151A (ja) | 1999-03-02 | 2002-11-12 | ベーリンガー インゲルハイム ファーマシューティカルズ インコーポレイテッド | カテプシンの可逆的インヒビターとして有用な化合物 |
| US6420364B1 (en) | 1999-09-13 | 2002-07-16 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compound useful as reversible inhibitors of cysteine proteases |
| EP1229934B1 (en) | 1999-10-01 | 2014-03-05 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
| CA2445591A1 (en) | 2001-04-27 | 2002-11-07 | The Procter & Gamble Company | Nitrogen heterocyclic compounds and compositions for controlling biofilms |
| AU2002359792A1 (en) * | 2001-12-18 | 2003-06-30 | Proteologics, Inc. | Methods and compositions for the inhibition of viral release |
| WO2003072754A2 (en) * | 2002-02-27 | 2003-09-04 | The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Conjugates of ligand, linker and cytotoxic agent and related compositions and methods of use |
| WO2006013552A2 (en) | 2004-08-02 | 2006-02-09 | Ramot At Tel Aviv University Ltd. | Articles of peptide nanostructures and method of forming the same |
| WO2006122408A1 (en) | 2005-05-18 | 2006-11-23 | Aegera Therapeutics Inc. | Bir domain binding compounds |
| EP1924245A2 (en) * | 2005-08-19 | 2008-05-28 | Government of the United States of America, Represented by the Secretary, Department of Health and Human Services | Topical formulations of histone deacetylase inhibitors and methods of using the same |
| US10004828B2 (en) * | 2005-10-11 | 2018-06-26 | Romat at Tel-Aviv University Ltd. | Self-assembled Fmoc-ff hydrogels |
| JP5419685B2 (ja) | 2006-05-16 | 2014-02-19 | ファーマサイエンス・インコーポレイテッド | Ｉａｐｂｉｒドメイン結合タンパク質 |
| JP5452223B2 (ja) * | 2006-07-24 | 2014-03-26 | テトラロジック ファーマシューティカルズ コーポレーション | Ｉａｐ阻害剤 |
| AU2008239730B2 (en) | 2007-04-12 | 2011-10-06 | Scinopharm Taiwan, Ltd. | Process for making galantamine |
| UY32099A (es) | 2008-09-11 | 2010-04-30 | Enanta Pharm Inc | Inhibidores macrocíclicos de serina proteasas de hepatitis c |
| US8283372B2 (en) | 2009-07-02 | 2012-10-09 | Tetralogic Pharmaceuticals Corp. | 2-(1H-indol-3-ylmethyl)-pyrrolidine dimer as a SMAC mimetic |
| EP2534170B1 (en) | 2010-02-12 | 2017-04-19 | Pharmascience Inc. | Iap bir domain binding compounds |
| CA2822556A1 (en) | 2010-12-30 | 2012-07-05 | Enanta Pharmaceuticals, Inc | Macrocyclic hepatitis c serine protease inhibitors |
| JP2014506255A (ja) | 2010-12-30 | 2014-03-13 | エナンタ ファーマシューティカルズ インコーポレイテッド | フェナントリジン大環状ｃ型肝炎セリンプロテアーゼ阻害剤 |
| US10201584B1 (en) | 2011-05-17 | 2019-02-12 | Abbvie Inc. | Compositions and methods for treating HCV |
| ES2690993T3 (es) | 2011-05-27 | 2018-11-23 | Ambrx, Inc. | Composiciones que contienen y métodos que implican derivados de dolastatina enlazados con aminoácidos no naturales y usos de los mismos |
| WO2015103490A1 (en) | 2014-01-03 | 2015-07-09 | Abbvie, Inc. | Solid antiviral dosage forms |
| WO2023033129A1 (ja) | 2021-09-03 | 2023-03-09 | 東レ株式会社 | 癌の治療及び／又は予防用医薬組成物 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816444A (en) * | 1987-07-10 | 1989-03-28 | Arizona Board Of Regents, Arizona State University | Cell growth inhibitory substance |
| US4879278A (en) * | 1989-05-16 | 1989-11-07 | Arizona Board Of Regents | Isolation and structural elucidation of the cytostatic linear depsipeptide dolastatin 15 |
| ATE190983T1 (de) * | 1991-08-09 | 2000-04-15 | Teikoku Hormone Mfg Co Ltd | Neue tetrapeptidderivate |
| RU2116312C1 (ru) * | 1992-05-20 | 1998-07-27 | Басф Акциенгезельшафт | Производные пептида или их соли, фармацевтическая композиция |
| US5530097A (en) * | 1994-08-01 | 1996-06-25 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Human cancer inhibitory peptide amides |
| US5504191A (en) * | 1994-08-01 | 1996-04-02 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Human cancer inhibitory pentapeptide methyl esters |
-
1995
- 1995-06-07 US US08/472,453 patent/US5831002A/en not_active Expired - Lifetime
-
1996
- 1996-06-03 AU AU61241/96A patent/AU725164B2/en not_active Ceased
- 1996-06-03 CN CNB961944676A patent/CN1182154C/zh not_active Expired - Fee Related
- 1996-06-03 PL PL96323723A patent/PL185762B1/pl unknown
- 1996-06-03 CA CA002219818A patent/CA2219818C/en not_active Expired - Fee Related
- 1996-06-03 CN CNB961944684A patent/CN1182153C/zh not_active Expired - Fee Related
- 1996-06-03 AU AU61242/96A patent/AU725170B2/en not_active Ceased
- 1996-06-03 IL IL12221696A patent/IL122216A/en not_active IP Right Cessation
- 1996-06-03 UA UA98010069A patent/UA46775C2/uk unknown
- 1996-06-03 HU HU9801817A patent/HU228073B1/hu not_active IP Right Cessation
- 1996-06-03 PT PT96918660T patent/PT832104E/pt unknown
- 1996-06-03 CZ CZ19973763A patent/CZ293682B6/cs not_active IP Right Cessation
- 1996-06-03 NZ NZ310443A patent/NZ310443A/en not_active IP Right Cessation
- 1996-06-03 JP JP50013297A patent/JP4221062B2/ja not_active Expired - Fee Related
- 1996-06-03 ES ES96918660T patent/ES2186783T3/es not_active Expired - Lifetime
- 1996-06-03 ES ES96918661T patent/ES2188759T3/es not_active Expired - Lifetime
- 1996-06-03 DK DK96918661T patent/DK0871656T3/da active
- 1996-06-03 DK DK96918660T patent/DK0832104T3/da active
- 1996-06-03 SI SI9630539T patent/SI0832104T1/xx unknown
- 1996-06-03 IL IL12221596A patent/IL122215A/xx not_active IP Right Cessation
- 1996-06-03 PT PT96918661T patent/PT871656E/pt unknown
- 1996-06-03 JP JP50013197A patent/JP3957751B2/ja not_active Expired - Fee Related
- 1996-06-03 RO RO97-02254A patent/RO119783B1/ro unknown
- 1996-06-03 WO PCT/EP1996/002393 patent/WO1996040752A1/en active IP Right Grant
- 1996-06-03 MX MX9709146A patent/MX9709146A/es unknown
- 1996-06-03 AT AT96918661T patent/ATE224910T1/de active
- 1996-06-03 MX MX9709147A patent/MX9709147A/es unknown
- 1996-06-03 TR TR97/01544T patent/TR199701544T1/xx unknown
- 1996-06-03 CA CA002219819A patent/CA2219819C/en not_active Expired - Fee Related
- 1996-06-03 KR KR1019970709063A patent/KR100437985B1/ko not_active IP Right Cessation
- 1996-06-03 UA UA98010070A patent/UA46776C2/uk unknown
- 1996-06-03 DE DE69623992T patent/DE69623992T2/de not_active Expired - Lifetime
- 1996-06-03 NZ NZ310444A patent/NZ310444A/xx not_active IP Right Cessation
- 1996-06-03 MY MYPI96002155A patent/MY119042A/en unknown
- 1996-06-03 SK SK1653-97A patent/SK282466B6/sk not_active IP Right Cessation
- 1996-06-03 BR BR9609423A patent/BR9609423A/pt not_active Application Discontinuation
- 1996-06-03 DE DE69623472T patent/DE69623472T2/de not_active Expired - Lifetime
- 1996-06-03 HU HU9801910A patent/HU228071B1/hu not_active IP Right Cessation
- 1996-06-03 BR BR9609424-9A patent/BR9609424A/pt not_active Application Discontinuation
- 1996-06-03 EP EP96918661A patent/EP0871656B1/en not_active Expired - Lifetime
- 1996-06-03 RO RO97-02264A patent/RO118953B1/ro unknown
- 1996-06-03 KR KR1019970709064A patent/KR100437986B1/ko not_active IP Right Cessation
- 1996-06-03 TR TR97/01545T patent/TR199701545T1/xx unknown
- 1996-06-03 PL PL96323726A patent/PL185763B1/pl unknown
- 1996-06-03 AT AT96918660T patent/ATE223431T1/de active
- 1996-06-03 WO PCT/EP1996/002392 patent/WO1996040751A1/en active IP Right Grant
- 1996-06-03 EP EP96918660A patent/EP0832104B1/en not_active Expired - Lifetime
- 1996-06-03 CZ CZ19973765A patent/CZ293683B6/cs not_active IP Right Cessation
- 1996-06-03 SI SI9630550T patent/SI0871656T1/xx unknown
- 1996-06-04 MY MYPI96002170A patent/MY124487A/en unknown
- 1996-06-06 AR ARP960102981A patent/AR003427A1/es active IP Right Grant
- 1996-06-06 ZA ZA9604710A patent/ZA964710B/xx unknown
- 1996-06-06 HR HR08/472,453A patent/HRP960277A2/hr not_active Application Discontinuation
- 1996-06-06 HR HR08/472,453A patent/HRP960257A2/hr not_active Application Discontinuation
- 1996-06-06 AR ARP960102980A patent/AR003136A1/es active IP Right Grant
- 1996-06-06 ZA ZA9604711A patent/ZA964711B/xx unknown
- 1996-06-07 CO CO96029751A patent/CO4700527A1/es unknown
- 1996-06-07 CO CO96029749A patent/CO4700526A1/es unknown
- 1996-06-07 TW TW085106866A patent/TW508357B/zh not_active IP Right Cessation
- 1996-10-02 TW TW085106867A patent/TW424096B/zh not_active IP Right Cessation
-
1997
- 1997-12-05 NO NO19975710A patent/NO318384B1/no not_active IP Right Cessation
- 1997-12-05 NO NO19975711A patent/NO317670B1/no not_active IP Right Cessation
- 1997-12-18 BG BG102125A patent/BG102125A/xx unknown
- 1997-12-29 BG BG102152A patent/BG102152A/xx unknown
Also Published As
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| CHAD | Change of the owner's name or address (par. 44 patent law, par. patentforskriften) |
Owner name: ABBVIE DEUTSCHLAND GMBH & CO AG, DE |
|
| MM1K | Lapsed by not paying the annual fees |