CA2383988A1 - Indole-containing and combretastatin-related anti-mitotic and anti-tubulin polymerization agents - Google Patents
Indole-containing and combretastatin-related anti-mitotic and anti-tubulin polymerization agents Download PDFInfo
- Publication number
- CA2383988A1 CA2383988A1 CA002383988A CA2383988A CA2383988A1 CA 2383988 A1 CA2383988 A1 CA 2383988A1 CA 002383988 A CA002383988 A CA 002383988A CA 2383988 A CA2383988 A CA 2383988A CA 2383988 A1 CA2383988 A1 CA 2383988A1
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- Prior art keywords
- compound
- alkyl
- hydrogen
- aryl
- carbon atoms
- Prior art date
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- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title abstract description 65
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title abstract description 33
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title abstract description 33
- LGZKGOGODCLQHG-CYBMUJFWSA-N 5-[(2r)-2-hydroxy-2-(3,4,5-trimethoxyphenyl)ethyl]-2-methoxyphenol Chemical compound C1=C(O)C(OC)=CC=C1C[C@@H](O)C1=CC(OC)=C(OC)C(OC)=C1 LGZKGOGODCLQHG-CYBMUJFWSA-N 0.000 title description 7
- 230000002927 anti-mitotic effect Effects 0.000 title description 7
- LGZKGOGODCLQHG-UHFFFAOYSA-N combretastatin Natural products C1=C(O)C(OC)=CC=C1CC(O)C1=CC(OC)=C(OC)C(OC)=C1 LGZKGOGODCLQHG-UHFFFAOYSA-N 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 69
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 37
- MQLACMBJVPINKE-UHFFFAOYSA-N 10-[(3-hydroxy-4-methoxyphenyl)methylidene]anthracen-9-one Chemical compound C1=C(O)C(OC)=CC=C1C=C1C2=CC=CC=C2C(=O)C2=CC=CC=C21 MQLACMBJVPINKE-UHFFFAOYSA-N 0.000 claims abstract description 23
- 201000011510 cancer Diseases 0.000 claims abstract description 20
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- 210000004881 tumor cell Anatomy 0.000 claims abstract description 9
- 230000008685 targeting Effects 0.000 claims abstract description 5
- 102000004243 Tubulin Human genes 0.000 claims description 39
- 108090000704 Tubulin Proteins 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 25
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 229910019142 PO4 Inorganic materials 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 239000010452 phosphate Substances 0.000 claims description 15
- -1 phosphate ester Chemical class 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 12
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 7
- 210000003169 central nervous system Anatomy 0.000 claims description 5
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- 125000000217 alkyl group Chemical group 0.000 claims 18
- 239000001257 hydrogen Substances 0.000 claims 16
- 125000004432 carbon atom Chemical group C* 0.000 claims 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 9
- 150000001768 cations Chemical class 0.000 claims 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- 125000003277 amino group Chemical group 0.000 claims 3
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 101150009274 nhr-1 gene Proteins 0.000 claims 3
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- 201000010099 disease Diseases 0.000 claims 1
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- 125000001680 trimethoxyphenyl group Chemical group 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 description 33
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 30
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- HVXBOLULGPECHP-UHFFFAOYSA-N combretastatin A4 Natural products C1=C(O)C(OC)=CC=C1C=CC1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-UHFFFAOYSA-N 0.000 description 21
- HVXBOLULGPECHP-WAYWQWQTSA-N Combretastatin A4 Chemical compound C1=C(O)C(OC)=CC=C1\C=C/C1=CC(OC)=C(OC)C(OC)=C1 HVXBOLULGPECHP-WAYWQWQTSA-N 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 16
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 15
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- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- KLLLJCACIRKBDT-UHFFFAOYSA-N 2-phenyl-1H-indole Chemical class N1C2=CC=CC=C2C=C1C1=CC=CC=C1 KLLLJCACIRKBDT-UHFFFAOYSA-N 0.000 description 9
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- OWPCHSCAPHNHAV-LMONGJCWSA-N rhizoxin Chemical compound C/C([C@H](OC)[C@@H](C)[C@@H]1C[C@H](O)[C@]2(C)O[C@@H]2/C=C/[C@@H](C)[C@]2([H])OC(=O)C[C@@](C2)(C[C@@H]2O[C@H]2C(=O)O1)[H])=C\C=C\C(\C)=C\C1=COC(C)=N1 OWPCHSCAPHNHAV-LMONGJCWSA-N 0.000 description 9
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- 238000006243 chemical reaction Methods 0.000 description 8
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 230000000259 anti-tumor effect Effects 0.000 description 7
- 239000003080 antimitotic agent Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 7
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 5
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
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- VXNQMUVMEIGUJW-XNOMRPDFSA-L disodium;[2-methoxy-5-[(z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl] phosphate Chemical compound [Na+].[Na+].C1=C(OP([O-])([O-])=O)C(OC)=CC=C1\C=C/C1=CC(OC)=C(OC)C(OC)=C1 VXNQMUVMEIGUJW-XNOMRPDFSA-L 0.000 description 4
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- ILUSBJDVXKZYEP-UHFFFAOYSA-N 4-(aminomethyl)oxan-4-ol;hydrochloride Chemical compound Cl.NCC1(O)CCOCC1 ILUSBJDVXKZYEP-UHFFFAOYSA-N 0.000 description 3
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- PMGCVNJAFPSBDK-UHFFFAOYSA-N [6-methoxy-2-(4-methoxyphenyl)-1h-indol-3-yl]-(3,4,5-trimethoxyphenyl)methanone Chemical compound C1=CC(OC)=CC=C1C1=C(C(=O)C=2C=C(OC)C(OC)=C(OC)C=2)C2=CC=C(OC)C=C2N1 PMGCVNJAFPSBDK-UHFFFAOYSA-N 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/22—Amides of acids of phosphorus
- C07F9/24—Esteramides
- C07F9/2454—Esteramides the amide moiety containing a substituent or a structure which is considered as characteristic
- C07F9/247—Esteramides the amide moiety containing a substituent or a structure which is considered as characteristic of aromatic amines (N-C aromatic linkage)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
- C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US15463999P | 1999-09-17 | 1999-09-17 | |
| US60/154,639 | 1999-09-17 | ||
| PCT/US2000/025408 WO2001019794A2 (en) | 1999-09-17 | 2000-09-15 | Indole-containing and combretastatin-related anti-mitotic and anti-tubulin polymerization agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2383988A1 true CA2383988A1 (en) | 2001-03-22 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002383988A Abandoned CA2383988A1 (en) | 1999-09-17 | 2000-09-15 | Indole-containing and combretastatin-related anti-mitotic and anti-tubulin polymerization agents |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20070082872A1 (enExample) |
| EP (1) | EP1214298B1 (enExample) |
| JP (1) | JP4187441B2 (enExample) |
| AU (1) | AU777725B2 (enExample) |
| CA (1) | CA2383988A1 (enExample) |
| WO (1) | WO2001019794A2 (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2408220A1 (en) * | 2000-05-09 | 2001-11-15 | George R. Pettit | Antitubulin assembly and cell growth inhibitor denominated "dioxostatin" |
| EP1289952A1 (en) | 2000-05-31 | 2003-03-12 | AstraZeneca AB | Indole derivatives with vascular damaging activity |
| AUPR283801A0 (en) * | 2001-02-01 | 2001-03-01 | Australian National University, The | Chemical compounds and methods |
| US7632955B2 (en) | 2001-12-13 | 2009-12-15 | National Health Research Institutes | Indole compounds |
| TWI317634B (en) | 2001-12-13 | 2009-12-01 | Nat Health Research Institutes | Aroyl indoles compounds |
| US7528165B2 (en) | 2001-12-13 | 2009-05-05 | National Health Research Institutes | Indole compounds |
| EP1515716A2 (en) | 2002-04-03 | 2005-03-23 | Astrazeneca AB | Indole derivatives having anti-angiogenetic activity |
| EP1506960B1 (en) | 2003-08-07 | 2011-04-06 | National Health Research Institutes | Indole compounds as inhibitors of tubulin polymerisation for the treatment of angiogenesis-related disorders |
| US7456214B2 (en) * | 2004-05-03 | 2008-11-25 | Baylor University | Chromene-containing compounds with anti-tubulin and vascular targeting activity |
| EP1778252A4 (en) * | 2004-08-11 | 2010-01-27 | Williamsburg Holdings Llc | NON-CARDIOTOXIC PHARMACEUTICAL COMPOUNDS |
| US7456289B2 (en) * | 2004-12-31 | 2008-11-25 | National Health Research Institutes | Anti-tumor compounds |
| EP1896391B1 (en) * | 2005-06-14 | 2015-08-12 | Baylor University | Combretastatin analogs with tubulin binding activity |
| CA2640678C (en) | 2006-02-03 | 2015-03-31 | Bionomics Limited | Substituted benzofurans, benzothiophenes, benzoselenophenes and indoles and their use as tubulin polymerisation inhibitors |
| EP2150112A1 (en) * | 2007-04-26 | 2010-02-10 | Merck & Co., Inc. | 2-substituted indole derivatives as calcium channel blockers |
| NZ598489A (en) | 2009-08-27 | 2014-03-28 | Bionomics Ltd | Combination therapy for treating proliferative diseases |
| CN102596929A (zh) | 2009-08-27 | 2012-07-18 | 生物学特性有限公司 | 黄斑变性的治疗 |
| IT1399130B1 (it) | 2010-04-01 | 2013-04-05 | Consiglio Nazionale Ricerche | Derivati indolici e loro uso in campo medico. |
| WO2014089177A2 (en) | 2012-12-04 | 2014-06-12 | Massachusetts Institute Of Technology | Compounds, conjugates and compositions of epipolythiodiketopiperazines and polythiodiketopiperazines |
| CA2905509A1 (en) | 2013-03-15 | 2014-09-18 | Memorial Sloan-Kettering Cancer Center | Hsp90-targeted cardiac imaging and therapy |
| CN104098499B (zh) * | 2013-04-08 | 2016-05-04 | 上海医药工业研究院 | 5-苄氧基-2-(4-苄氧基苯基)-3-甲基-1h-吲哚的制备方法 |
| US9944597B2 (en) | 2013-09-16 | 2018-04-17 | The Board Of Regents Of The University Of Texas System | Polysubstituted pyrroles having microtubule-disrupting, cytotoxic and antitumor activities and methods of use thereof |
| CN104262229B (zh) * | 2014-08-18 | 2016-10-05 | 广东颐正达医药科技有限公司 | 一种2-苯基取代-3-苯甲酰基取代吲哚的制备方法 |
| US10918627B2 (en) | 2016-05-11 | 2021-02-16 | Massachusetts Institute Of Technology | Convergent and enantioselective total synthesis of Communesin analogs |
| WO2018209239A1 (en) | 2017-05-11 | 2018-11-15 | Massachusetts Institute Of Technology | Potent agelastatin derivatives as modulators for cancer invasion and metastasis |
| CN107652194B (zh) * | 2017-08-08 | 2020-02-28 | 首都医科大学附属北京天坛医院 | 一类用于治疗神经系统疾病的化合物 |
| US10640508B2 (en) | 2017-10-13 | 2020-05-05 | Massachusetts Institute Of Technology | Diazene directed modular synthesis of compounds with quaternary carbon centers |
| US11535634B2 (en) | 2019-06-05 | 2022-12-27 | Massachusetts Institute Of Technology | Compounds, conjugates, and compositions of epipolythiodiketopiperazines and polythiodiketopiperazines and uses thereof |
| US12030888B2 (en) | 2021-02-24 | 2024-07-09 | Massachusetts Institute Of Technology | Himastatin derivatives, and processes of preparation thereof, and uses thereof |
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| JP2963288B2 (ja) * | 1992-01-14 | 1999-10-18 | 株式会社海洋バイオテクノロジー研究所 | 水中有害付着生物防除剤 |
| US5596106A (en) * | 1994-07-15 | 1997-01-21 | Eli Lilly And Company | Cannabinoid receptor antagonists |
| US5886025A (en) * | 1997-03-06 | 1999-03-23 | Baylor University | Anti-mitotic agents which inhibit tubulin polymerization |
| US5948808A (en) * | 1997-03-07 | 1999-09-07 | The Texas A&M University System | Indole-3-carbinol, diindolylmethane and substituted analogs as antiestrogens |
| US6001868A (en) * | 1997-05-30 | 1999-12-14 | The Regents Of The University Of California | Indole-3-carbinol (I3C) derivatives and methods |
| US6150395A (en) * | 1997-05-30 | 2000-11-21 | The Regents Of The University Of California | Indole-3-carbinol (I3C) derivatives and methods |
| JP2002500184A (ja) * | 1998-01-09 | 2002-01-08 | アリゾナ ボード オブ リーゼンツ | フェンスタチンとそのプロドラッグの合成 |
| US6410584B1 (en) * | 1998-01-14 | 2002-06-25 | Cell Pathways, Inc. | Method for inhibiting neoplastic cells with indole derivatives |
| US6162930A (en) * | 1998-03-06 | 2000-12-19 | Baylor University | Anti-mitotic agents which inhibit tubulin polymerization |
| DE19946301A1 (de) * | 1998-04-02 | 2001-04-19 | Asta Medica Ag | Indolyl-3-glyoxylsäure-Derivate mit therapeutisch wertvollen Eigenschaften |
| DE19814838C2 (de) * | 1998-04-02 | 2001-01-18 | Asta Medica Ag | Indolyl-3-glyoxylsäure-Derivate mit Antitumorwirkung |
| US6110963A (en) * | 1998-05-12 | 2000-08-29 | American Home Products Corporation | Aryl-oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia |
| US6166069A (en) * | 1998-05-12 | 2000-12-26 | American Home Products Corporation | Phenyl oxo-acetic acids useful in the treatment of insulin resistance and hyperglycemia |
| US6358992B1 (en) * | 1998-11-25 | 2002-03-19 | Cell Pathways, Inc. | Method of inhibiting neoplastic cells with indole derivatives |
| JP2002537262A (ja) * | 1999-02-18 | 2002-11-05 | オキシジェン，インコーポレイティド | 血管破壊のターゲッティングに使用するための組成物および方法 |
| US6521658B1 (en) * | 1999-05-28 | 2003-02-18 | Abbott Laboratories | Cell proliferation inhibitors |
| US6849656B1 (en) * | 1999-09-17 | 2005-02-01 | Baylor University | Indole-containing and combretastatin-related anti-mitotic and anti-tubulin polymerization agents |
| US6323228B1 (en) * | 2000-09-15 | 2001-11-27 | Abbott Laboratories | 3-substituted indole angiogenesis inhibitors |
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| AU7493400A (en) | 2001-04-17 |
| WO2001019794A2 (en) | 2001-03-22 |
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| JP4187441B2 (ja) | 2008-11-26 |
| EP1214298B1 (en) | 2012-05-30 |
| US20070082872A1 (en) | 2007-04-12 |
| AU777725B2 (en) | 2004-10-28 |
| WO2001019794A3 (en) | 2001-09-27 |
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