ES2380574T3 - Derivados de isoindolina farmacéuticamente activos - Google Patents
Derivados de isoindolina farmacéuticamente activos Download PDFInfo
- Publication number
- ES2380574T3 ES2380574T3 ES10176420T ES10176420T ES2380574T3 ES 2380574 T3 ES2380574 T3 ES 2380574T3 ES 10176420 T ES10176420 T ES 10176420T ES 10176420 T ES10176420 T ES 10176420T ES 2380574 T3 ES2380574 T3 ES 2380574T3
- Authority
- ES
- Spain
- Prior art keywords
- methoxyphenyl
- ethoxy
- mmol
- mixture
- carbon atoms
- 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.)
- Expired - Lifetime
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- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical class C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 title description 6
- -1 Cyclopropyl-N - {- [(1S) -1- (3-ethoxy-4-methoxyphenyl) -2- (methylsulfonyl) ethyl] -3-oxoisoindoline-4-yl} carboxamide Chemical compound 0.000 claims abstract description 106
- 238000011282 treatment Methods 0.000 claims abstract description 20
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 13
- 239000002253 acid Substances 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 47
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 30
- QDZOBXFRIVOQBR-LJQANCHMSA-N n-[2-[(1s)-1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-3-oxo-1h-isoindol-4-yl]cyclopropanecarboxamide Chemical compound C1=C(OC)C(OCC)=CC([C@@H](CS(C)(=O)=O)N2C(C3=C(NC(=O)C4CC4)C=CC=C3C2)=O)=C1 QDZOBXFRIVOQBR-LJQANCHMSA-N 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 10
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 8
- 229940124597 therapeutic agent Drugs 0.000 claims description 6
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 3
- 208000024908 graft versus host disease Diseases 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 125000002345 steroid group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 237
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 210
- 239000000203 mixture Substances 0.000 description 154
- 239000007787 solid Substances 0.000 description 149
- 125000004432 carbon atom Chemical group C* 0.000 description 147
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 145
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 104
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 98
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 87
- 150000001875 compounds Chemical class 0.000 description 85
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 72
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- 238000005160 1H NMR spectroscopy Methods 0.000 description 68
- 239000003921 oil Substances 0.000 description 68
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 66
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 65
- 239000000725 suspension Substances 0.000 description 62
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 60
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 59
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 59
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 56
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
- 239000002904 solvent Substances 0.000 description 54
- 125000000217 alkyl group Chemical group 0.000 description 52
- 229910052739 hydrogen Inorganic materials 0.000 description 44
- 239000001257 hydrogen Substances 0.000 description 42
- 239000012267 brine Substances 0.000 description 41
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 41
- 239000000741 silica gel Substances 0.000 description 39
- 229910002027 silica gel Inorganic materials 0.000 description 39
- 239000000243 solution Substances 0.000 description 35
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 35
- 238000000034 method Methods 0.000 description 34
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- 238000004587 chromatography analysis Methods 0.000 description 33
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 32
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 31
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 31
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 30
- 206010028980 Neoplasm Diseases 0.000 description 29
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 28
- 239000000460 chlorine Substances 0.000 description 28
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 28
- 235000019341 magnesium sulphate Nutrition 0.000 description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 26
- 238000010992 reflux Methods 0.000 description 26
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 25
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 24
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 24
- 125000000753 cycloalkyl group Chemical group 0.000 description 23
- 125000001589 carboacyl group Chemical group 0.000 description 21
- 230000033115 angiogenesis Effects 0.000 description 19
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 19
- 201000010099 disease Diseases 0.000 description 19
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 18
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 17
- 125000004663 dialkyl amino group Chemical group 0.000 description 17
- 239000012074 organic phase Substances 0.000 description 15
- 210000001744 T-lymphocyte Anatomy 0.000 description 14
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 14
- 125000001475 halogen functional group Chemical group 0.000 description 14
- 235000017557 sodium bicarbonate Nutrition 0.000 description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 241000725303 Human immunodeficiency virus Species 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- BHJUWEUNUCJYER-UHFFFAOYSA-N 4-amino-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(N)C=CC=C3C2=O)=O)=C1 BHJUWEUNUCJYER-UHFFFAOYSA-N 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
- 241000124008 Mammalia Species 0.000 description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 11
- 230000000875 corresponding effect Effects 0.000 description 11
- 238000004519 manufacturing process Methods 0.000 description 11
- 125000001424 substituent group Chemical group 0.000 description 11
- 201000011510 cancer Diseases 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 230000001404 mediated effect Effects 0.000 description 10
- 239000012258 stirred mixture Substances 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- GFISDBXSWQMOND-UHFFFAOYSA-N 2,5-dimethoxyoxolane Chemical compound COC1CCC(OC)O1 GFISDBXSWQMOND-UHFFFAOYSA-N 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 125000003282 alkyl amino group Chemical group 0.000 description 8
- 125000004093 cyano group Chemical group *C#N 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 8
- 125000001188 haloalkyl group Chemical group 0.000 description 8
- 102000004127 Cytokines Human genes 0.000 description 7
- 208000031886 HIV Infections Diseases 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 7
- 241000700605 Viruses Species 0.000 description 7
- 235000011054 acetic acid Nutrition 0.000 description 7
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- 239000008107 starch Substances 0.000 description 7
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- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- 206010006895 Cachexia Diseases 0.000 description 6
- 208000011231 Crohn disease Diseases 0.000 description 6
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- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- 125000001118 alkylidene group Chemical group 0.000 description 6
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- 239000012043 crude product Substances 0.000 description 6
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 6
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 6
- QKHSAVPFILQVGW-UHFFFAOYSA-N 4,5-diamino-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]isoindole-1,3-dione Chemical compound C1=C(OC)C(OCC)=CC(C(CS(C)(=O)=O)N2C(C3=C(N)C(N)=CC=C3C2=O)=O)=C1 QKHSAVPFILQVGW-UHFFFAOYSA-N 0.000 description 5
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- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 5
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Classifications
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- 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
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/46—Iso-indoles; Hydrogenated iso-indoles with an oxygen atom in position 1
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- 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
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- Health & Medical Sciences (AREA)
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- Communicable Diseases (AREA)
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- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Biotechnology (AREA)
- Physical Education & Sports Medicine (AREA)
- AIDS & HIV (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
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| US708199 | 1985-03-04 | ||
| US16516899P | 1999-11-12 | 1999-11-12 | |
| US165168P | 1999-11-12 | ||
| US59034400A | 2000-06-08 | 2000-06-08 | |
| US590344 | 2000-06-08 | ||
| US09/708,199 US6667316B1 (en) | 1999-11-12 | 2000-11-08 | Pharmaceutically active isoindoline derivatives |
Publications (1)
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| ES2380574T3 true ES2380574T3 (es) | 2012-05-16 |
Family
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| Application Number | Title | Priority Date | Filing Date |
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| ES10176420T Expired - Lifetime ES2380574T3 (es) | 1999-11-12 | 2000-11-09 | Derivados de isoindolina farmacéuticamente activos |
| ES00977095T Expired - Lifetime ES2282147T3 (es) | 1999-11-12 | 2000-11-09 | Derivados de isoindolina farmaceuticamente activos. |
| ES10176390T Expired - Lifetime ES2381174T3 (es) | 1999-11-12 | 2000-11-09 | Derivados de isoindolina farmacéuticamente activos |
| ES06009632T Expired - Lifetime ES2363933T3 (es) | 1999-11-12 | 2000-11-09 | Derivados de isoindolina farmacéuticamente activos. |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
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| ES00977095T Expired - Lifetime ES2282147T3 (es) | 1999-11-12 | 2000-11-09 | Derivados de isoindolina farmaceuticamente activos. |
| ES10176390T Expired - Lifetime ES2381174T3 (es) | 1999-11-12 | 2000-11-09 | Derivados de isoindolina farmacéuticamente activos |
| ES06009632T Expired - Lifetime ES2363933T3 (es) | 1999-11-12 | 2000-11-09 | Derivados de isoindolina farmacéuticamente activos. |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US6667316B1 (https=) |
| EP (4) | EP2255801B1 (https=) |
| JP (1) | JP5116201B2 (https=) |
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| AU (2) | AU782409B2 (https=) |
| CA (1) | CA2392081C (https=) |
| CY (2) | CY1107610T1 (https=) |
| DE (1) | DE60034139T2 (https=) |
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| PT (2) | PT1228071E (https=) |
| SI (1) | SI1228071T1 (https=) |
| WO (1) | WO2001034606A1 (https=) |
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| US6429221B1 (en) | 1994-12-30 | 2002-08-06 | Celgene Corporation | Substituted imides |
| US6518281B2 (en) * | 1995-08-29 | 2003-02-11 | Celgene Corporation | Immunotherapeutic agents |
| RU2188819C2 (ru) * | 1996-08-12 | 2002-09-10 | Селджин Корпорейшн | НОВЫЕ ИММУНОТЕРАПЕВТИЧЕСКИЕ СОЕДИНЕНИЯ, СОДЕРЖАЩАЯ ИХ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И СПОСОБ СНИЖЕНИЯ УРОВНЕЙ ФДЭ, TNFα И NFκB |
| US8030343B2 (en) * | 2000-06-08 | 2011-10-04 | Celgene Corporation | Pharmaceutically active isoindoline derivatives |
| US7491634B2 (en) * | 2006-04-28 | 2009-02-17 | Asm International N.V. | Methods for forming roughened surfaces and applications thereof |
| US7893071B2 (en) | 2001-04-23 | 2011-02-22 | University Of Virginia Patent Foundation | Synthesis and evaluation of novel phthalimide mimics as anti-angiogenic |
| WO2003014315A2 (en) * | 2001-08-06 | 2003-02-20 | The Children's Medical Center Corporation | Synthesis and anti-tumor activity of nitrogen substituted thalidomide analogs |
| US6962940B2 (en) * | 2002-03-20 | 2005-11-08 | Celgene Corporation | (+)-2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione: methods of using and compositions thereof |
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| US20050203142A1 (en) * | 2002-10-24 | 2005-09-15 | Zeldis Jerome B. | Methods of using and compositions comprising immunomodulatory compounds for treatment, modification and management of pain |
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| CN111170925B (zh) * | 2020-01-09 | 2023-01-17 | 常州大学 | 作为pde2/4双重抑制剂的邻苯二甲酰亚胺类化合物及其制备方法 |
| TW202237580A (zh) * | 2020-12-14 | 2022-10-01 | 美商拜歐斯瑞克斯公司 | Pde4降解劑、醫藥組合物及治療應用 |
| JP7605536B2 (ja) * | 2021-03-15 | 2024-12-24 | 深▲せん▼福沃薬業有限公司 | エストロゲン受容体モジュレーター |
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| US4173652A (en) | 1976-12-18 | 1979-11-06 | Akzona Incorporated | Pharmaceutical hydroxamic acid compositions and uses thereof |
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| US5801195A (en) | 1994-12-30 | 1998-09-01 | Celgene Corporation | Immunotherapeutic aryl amides |
| NZ305940A (en) | 1995-07-26 | 1999-05-28 | Pfizer | N-(aroyl)glycine hydroxamic acid derivatives and related compounds that inhibit the production of tnf and are useful in treating asthma |
| US5728845A (en) * | 1995-08-29 | 1998-03-17 | Celgene Corporation | Immunotherapeutic nitriles |
| US5728844A (en) * | 1995-08-29 | 1998-03-17 | Celgene Corporation | Immunotherapeutic agents |
| US5658940A (en) | 1995-10-06 | 1997-08-19 | Celgene Corporation | Succinimide and maleimide cytokine inhibitors |
| JP4358908B2 (ja) | 1996-01-02 | 2009-11-04 | アヴェンティス ファーマシューティカルズ インコーポレイテッド | 置換（アリール、ヘテロアリール、アリールメチル又はヘテロアリールメチル）ヒドロキサム酸化合物 |
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| CA2295295A1 (en) * | 1997-07-31 | 1999-02-11 | Celgene Corporation | Substituted alkanohydroxamic acids and method of reducing tnf.alpha. levels |
| US6020358A (en) * | 1998-10-30 | 2000-02-01 | Celgene Corporation | Substituted phenethylsulfones and method of reducing TNFα levels |
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2000
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- 2000-11-09 AT AT00977095T patent/ATE357913T1/de active
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