ZA200304262B - Tetralone derivatives as antitumor agents. - Google Patents
Tetralone derivatives as antitumor agents. Download PDFInfo
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- ZA200304262B ZA200304262B ZA200304262A ZA200304262A ZA200304262B ZA 200304262 B ZA200304262 B ZA 200304262B ZA 200304262 A ZA200304262 A ZA 200304262A ZA 200304262 A ZA200304262 A ZA 200304262A ZA 200304262 B ZA200304262 B ZA 200304262B
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- South Africa
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- compound
- tetrahydro
- formula
- alkyl
- composition
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- 239000002246 antineoplastic agent Substances 0.000 title description 3
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical class C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 71
- -1 trifluoromethyl- Chemical group 0.000 claims description 58
- 239000002253 acid Substances 0.000 claims description 39
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 13
- 102000003964 Histone deacetylase Human genes 0.000 claims description 11
- 108090000353 Histone deacetylase Proteins 0.000 claims description 11
- ZXKINMCYCKHYFR-UHFFFAOYSA-N aminooxidanide Chemical compound [O-]N ZXKINMCYCKHYFR-UHFFFAOYSA-N 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 230000008569 process Effects 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 6
- 230000006907 apoptotic process Effects 0.000 claims description 6
- 239000003112 inhibitor Substances 0.000 claims description 6
- 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 claims description 5
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
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- 125000003118 aryl group Chemical group 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
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- 239000004480 active ingredient Substances 0.000 claims description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 230000004663 cell proliferation Effects 0.000 claims description 3
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- 239000000411 inducer Substances 0.000 claims description 3
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- 125000004494 ethyl ester group Chemical group 0.000 claims 1
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- 238000006243 chemical reaction Methods 0.000 description 44
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- 239000000243 solution Substances 0.000 description 23
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000012442 inert solvent Substances 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
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- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
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- 229960004132 diethyl ether Drugs 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 238000003756 stirring Methods 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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- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- 150000008064 anhydrides Chemical class 0.000 description 4
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
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- C07C233/57—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C233/60—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/10—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms
- C07D295/112—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- C07D295/116—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by doubly bound oxygen or sulphur atoms with the ring nitrogen atoms and the doubly bound oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings with the doubly bound oxygen or sulfur atoms directly attached to a carbocyclic ring
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/46—Oxygen atoms
- C07D213/50—Ketonic radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General 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)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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EP00126820 | 2000-12-07 |
Publications (1)
Publication Number | Publication Date |
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ZA200304262B true ZA200304262B (en) | 2004-08-30 |
Family
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Family Applications (1)
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ZA200304262A ZA200304262B (en) | 2000-12-07 | 2003-05-30 | Tetralone derivatives as antitumor agents. |
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JP (1) | JP4091431B2 (cs) |
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CN (1) | CN100340545C (cs) |
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BG (1) | BG107889A (cs) |
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HU (1) | HUP0400579A2 (cs) |
IL (1) | IL156133A0 (cs) |
MA (1) | MA26972A1 (cs) |
MX (1) | MXPA03004947A (cs) |
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PL (1) | PL365324A1 (cs) |
RU (1) | RU2288220C2 (cs) |
SK (1) | SK8512003A3 (cs) |
WO (1) | WO2002046144A1 (cs) |
YU (1) | YU45803A (cs) |
ZA (1) | ZA200304262B (cs) |
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US7148257B2 (en) | 2002-03-04 | 2006-12-12 | Merck Hdac Research, Llc | Methods of treating mesothelioma with suberoylanilide hydroxamic acid |
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GB0217777D0 (en) * | 2002-07-31 | 2002-09-11 | Novartis Ag | Organic compounds |
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JP2006509010A (ja) * | 2002-12-05 | 2006-03-16 | インペリアル・カレッジ・イノベイションズ・リミテッド | アポトーシスの制御 |
JP2006520796A (ja) * | 2003-03-17 | 2006-09-14 | タケダ サン ディエゴ インコーポレイテッド | ヒストンデアセチラーゼインヒビター |
PL1663194T3 (pl) | 2003-08-26 | 2011-01-31 | Merck Hdac Res Llc | Zastosowanie SAHA do leczenia międzybłoniaka |
US20070190022A1 (en) | 2003-08-29 | 2007-08-16 | Bacopoulos Nicholas G | Combination methods of treating cancer |
US20050137234A1 (en) * | 2003-12-19 | 2005-06-23 | Syrrx, Inc. | Histone deacetylase inhibitors |
WO2005065681A1 (en) * | 2003-12-19 | 2005-07-21 | Takeda San Diego, Inc. | N- hydroxy-3-(3-(1h-imidazol-2-yl)-phenyl)-acrylamide derivatives and related compounds as histone deacetylase (hdac) inhibitors for the treatment of cancer |
CA2561954A1 (en) * | 2004-04-05 | 2005-10-20 | Myogen, Inc. | Inhibition of nuclear export as a treatment for cardiac hypertrophy and heart failure |
WO2005099747A1 (en) * | 2004-04-14 | 2005-10-27 | Medical Research Council | Selective killing of cancer cells by induction of acetyltransferase via tnf-alpha and il-6 |
KR100632800B1 (ko) | 2004-10-21 | 2006-10-16 | 한국화학연구원 | 히스톤 디아세틸라제 저해활성을 갖는 신규한하이드록시아마이드 유도체 및 이의 제조 방법 |
EP1824831A2 (en) * | 2004-12-16 | 2007-08-29 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
JP2008540574A (ja) * | 2005-05-11 | 2008-11-20 | タケダ サン ディエゴ インコーポレイテッド | ヒストンデアセチラーゼ阻害剤 |
TWI365068B (en) | 2005-05-20 | 2012-06-01 | Merck Sharp & Dohme | Formulations of suberoylanilide hydroxamic acid and methods for producing same |
BRPI0613429A2 (pt) * | 2005-07-14 | 2009-02-10 | Takeda San Diego Inc | inibidores de histona desacetilase |
EP2275095A3 (en) | 2005-08-26 | 2011-08-17 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
EP2258359A3 (en) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation with sabcomelin |
EP2377530A3 (en) | 2005-10-21 | 2012-06-20 | Braincells, Inc. | Modulation of neurogenesis by PDE inhibition |
EP2314289A1 (en) | 2005-10-31 | 2011-04-27 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
WO2007084390A2 (en) * | 2006-01-13 | 2007-07-26 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
CA2650520A1 (en) | 2006-04-24 | 2008-01-31 | Gloucester Pharmaceuticals | Treatment of ras-expressing tumors |
CA2651813A1 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
WO2007134077A2 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | 5 ht receptor mediated neurogenesis |
AU2007292848A1 (en) | 2006-09-08 | 2008-03-13 | Braincells, Inc. | Combinations containing a 4-acylaminopyridine derivative |
US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
US10184933B2 (en) | 2013-10-01 | 2019-01-22 | The J. David Gladstone Industries | Compositions, systems and methods for gene expression noise drug screening and uses thereof |
EP3769757A3 (en) * | 2013-10-18 | 2021-10-06 | The General Hospital Corporation | Imaging histone deacetylases with a radiotracer using positron emission tomography |
EP3461488A1 (en) | 2017-09-27 | 2019-04-03 | Onxeo | Combination of a dbait molecule and a hdac inhibitor for treating cancer |
EP3461480A1 (en) | 2017-09-27 | 2019-04-03 | Onxeo | Combination of a dna damage response cell cycle checkpoint inhibitors and belinostat for treating cancer |
EP3946299A4 (en) * | 2019-03-29 | 2022-11-23 | Taiwanj Pharmaceuticals Co., Ltd. | BENZENE DERIVATIVES WITH EXTENDED PERIPHERAL ALKYL AND ALKENYL CHAINS AND PHARMACEUTICAL COMPOSITION COMPRISING THEM |
WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
WO2023041805A1 (en) | 2021-09-20 | 2023-03-23 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for improving the efficacy of hdac inhibitor therapy and predicting the response to treatment with hdac inhibitor |
WO2023194441A1 (en) | 2022-04-05 | 2023-10-12 | Istituto Nazionale Tumori Irccs - Fondazione G. Pascale | Combination of hdac inhibitors and statins for use in the treatment of pancreatic cancer |
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US4448730A (en) * | 1981-03-24 | 1984-05-15 | Riet Bartholomeus Van T | Hydroxybenzohydroxamic acids, benzamides and esters and related compounds as ribonucleotide reductase inhibitors |
JPS61176523A (ja) * | 1985-01-30 | 1986-08-08 | Teruhiko Beppu | 制癌剤 |
US5369108A (en) | 1991-10-04 | 1994-11-29 | Sloan-Kettering Institute For Cancer Research | Potent inducers of terminal differentiation and methods of use thereof |
US5637946A (en) * | 1993-10-28 | 1997-06-10 | Lockheed Corporation | Thermally energized electrical power source |
AUPO721997A0 (en) | 1997-06-06 | 1997-07-03 | Queensland Institute Of Medical Research, The | Anticancer compounds |
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2004
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Also Published As
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BG107889A (bg) | 2004-06-30 |
NO20032531L (no) | 2003-06-04 |
SK8512003A3 (en) | 2004-04-06 |
AU2002216074B2 (en) | 2006-01-05 |
WO2002046144A1 (en) | 2002-06-13 |
BR0115988A (pt) | 2004-01-13 |
AU1607402A (en) | 2002-06-18 |
MA26972A1 (fr) | 2004-12-20 |
IL156133A0 (en) | 2003-12-23 |
CZ20031833A3 (cs) | 2004-02-18 |
JP2004515488A (ja) | 2004-05-27 |
AR035659A1 (es) | 2004-06-23 |
PL365324A1 (en) | 2004-12-27 |
AU2002216074C1 (en) | 2006-12-07 |
NZ526051A (en) | 2004-12-24 |
EP1349830A1 (en) | 2003-10-08 |
CN100340545C (zh) | 2007-10-03 |
YU45803A (sh) | 2006-05-25 |
US20020065282A1 (en) | 2002-05-30 |
ECSP034642A (es) | 2003-07-25 |
CN1478072A (zh) | 2004-02-25 |
HRP20030451A2 (en) | 2005-04-30 |
HK1060875A1 (en) | 2004-08-27 |
KR20030077551A (ko) | 2003-10-01 |
RU2288220C2 (ru) | 2006-11-27 |
NO20032531D0 (no) | 2003-06-04 |
MXPA03004947A (es) | 2003-09-10 |
HUP0400579A2 (hu) | 2004-06-28 |
CA2430355A1 (en) | 2002-06-13 |
US6531472B2 (en) | 2003-03-11 |
JP4091431B2 (ja) | 2008-05-28 |
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