DE69912479T2 - 4- und 5-alkynyloxindole sowie 4- und 5-alkenyloxindole - Google Patents
4- und 5-alkynyloxindole sowie 4- und 5-alkenyloxindole Download PDFInfo
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- DE69912479T2 DE69912479T2 DE69912479T DE69912479T DE69912479T2 DE 69912479 T2 DE69912479 T2 DE 69912479T2 DE 69912479 T DE69912479 T DE 69912479T DE 69912479 T DE69912479 T DE 69912479T DE 69912479 T2 DE69912479 T2 DE 69912479T2
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- Germany
- Prior art keywords
- dihydro
- methylene
- radical
- pyrrol
- indol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 150000002475 indoles Chemical class 0.000 title 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 9
- -1 alkyl radical Chemical class 0.000 claims description 300
- 230000015572 biosynthetic process Effects 0.000 claims description 112
- 125000000623 heterocyclic group Chemical group 0.000 claims description 112
- 238000003786 synthesis reaction Methods 0.000 claims description 112
- 150000001875 compounds Chemical class 0.000 claims description 105
- 125000005843 halogen group Chemical group 0.000 claims description 49
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 35
- 150000005840 aryl radicals Chemical class 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 17
- WUWDLXZGHZSWQZ-WQLSENKSSA-N semaxanib Chemical compound N1C(C)=CC(C)=C1\C=C/1C2=CC=CC=C2NC\1=O WUWDLXZGHZSWQZ-WQLSENKSSA-N 0.000 claims description 16
- 125000004429 atom Chemical group 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 13
- YLQAQZFUXVPZGQ-LCYFTJDESA-N (3z)-5-ethynyl-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=C(C#C)C=C2\C1=C\C1=CC=CN1 YLQAQZFUXVPZGQ-LCYFTJDESA-N 0.000 claims description 12
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 12
- 239000000651 prodrug Substances 0.000 claims description 11
- 229940002612 prodrug Drugs 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 9
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- 125000003107 substituted aryl group Chemical group 0.000 claims description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 7
- 125000004104 aryloxy group Chemical group 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 7
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
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- QOXYBCGXASWZIY-VKAVYKQESA-N (3z)-4-[3-(3,4-dimethoxyphenyl)-3-hydroxyprop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=C(OC)C(OC)=CC=4)C=CC=C3NC\2=O)=C1OC QOXYBCGXASWZIY-VKAVYKQESA-N 0.000 claims description 4
- PBNDYRBZMZOPIF-OWBHPGMISA-N (3z)-4-[3-hydroxy-3-(1h-pyrrol-2-yl)prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4NC=CC=4)C=CC=C3NC\2=O)=C1OC PBNDYRBZMZOPIF-OWBHPGMISA-N 0.000 claims description 4
- FLUWNHUCLAWPKG-ATVHPVEESA-N (3z)-4-[3-hydroxy-3-(2,4,5-trimethoxyphenyl)prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C(=CC(OC)=C(OC)C=4)OC)C=CC=C3NC\2=O)=C1OC FLUWNHUCLAWPKG-ATVHPVEESA-N 0.000 claims description 4
- NSIKGWYDIJARHZ-VBKFSLOCSA-N (3z)-4-[3-hydroxy-3-(7-methoxy-1,3-benzodioxol-5-yl)prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=C(OC)C=5OCOC=5C=4)C=CC=C3NC\2=O)=C1OC NSIKGWYDIJARHZ-VBKFSLOCSA-N 0.000 claims description 4
- DTBCCPGQXHCCJH-RGEXLXHISA-N (3z)-5-(2-phenylethynyl)-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=C(C#CC=3C=CC=CC=3)C=C2\C1=C\C1=CC=CN1 DTBCCPGQXHCCJH-RGEXLXHISA-N 0.000 claims description 4
- GZSXMGUALNRWHL-XFXZXTDPSA-N (3z)-5-ethynyl-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=CC(=CC=C3NC\2=O)C#C)=C1OC GZSXMGUALNRWHL-XFXZXTDPSA-N 0.000 claims description 4
- RSEGQJSFDGPSHB-LGMDPLHJSA-N 2-[4-[1-hydroxy-3-[(3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-2-oxo-1h-indol-4-yl]prop-2-ynyl]-2-methoxyphenoxy]acetic acid Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=C(OC)C(OCC(O)=O)=CC=4)C=CC=C3NC\2=O)=C1OC RSEGQJSFDGPSHB-LGMDPLHJSA-N 0.000 claims description 4
- HKZCQULQCAPKRS-AQTBWJFISA-N 2-[4-[1-hydroxy-3-[(3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-2-oxo-1h-indol-4-yl]prop-2-ynyl]phenoxy]acetic acid Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=CC(OCC(O)=O)=CC=4)C=CC=C3NC\2=O)=C1OC HKZCQULQCAPKRS-AQTBWJFISA-N 0.000 claims description 4
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 4
- 239000002207 metabolite Substances 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- LLTZGYZYWGAACV-HKVBYMSFSA-N (3z)-1-[(e)-2-phenylethenyl]-3-(1h-pyrrol-2-ylmethylidene)indol-2-one Chemical compound C12=CC=CC=C2\C(=C\C=2NC=CC=2)C(=O)N1\C=C\C1=CC=CC=C1 LLTZGYZYWGAACV-HKVBYMSFSA-N 0.000 claims description 3
- CNELYFGFVRCQQO-ATVHPVEESA-N (3z)-3-(1h-pyrrol-2-ylmethylidene)-5-(2-thiophen-2-ylethynyl)-1h-indol-2-one Chemical compound O=C1NC2=CC=C(C#CC=3SC=CC=3)C=C2\C1=C\C1=CC=CN1 CNELYFGFVRCQQO-ATVHPVEESA-N 0.000 claims description 3
- SOYFKPDKCDIHMW-SSZFMOIBSA-N (3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-4-(2-pyridin-4-ylethynyl)-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC=4C=CN=CC=4)C=CC=C3NC\2=O)=C1OC SOYFKPDKCDIHMW-SSZFMOIBSA-N 0.000 claims description 3
- CIBQBCXWQYRSFJ-SDXDJHTJSA-N (3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-4-(3-phenoxyprop-1-ynyl)-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CCOC=4C=CC=CC=4)C=CC=C3NC\2=O)=C1OC CIBQBCXWQYRSFJ-SDXDJHTJSA-N 0.000 claims description 3
- ZFTNBLBWWCOJCD-QINSGFPZSA-N (3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-5-(2-trimethylsilylethynyl)-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=CC(=CC=C3NC\2=O)C#C[Si](C)(C)C)=C1OC ZFTNBLBWWCOJCD-QINSGFPZSA-N 0.000 claims description 3
- XWDAYWGNKHFMGK-GDNBJRDFSA-N (3z)-3-[(5-methyl-1h-imidazol-4-yl)methylidene]-5-(2-trimethylsilylethynyl)-1h-indol-2-one Chemical compound N1=CNC(\C=C/2C3=CC(=CC=C3NC\2=O)C#C[Si](C)(C)C)=C1C XWDAYWGNKHFMGK-GDNBJRDFSA-N 0.000 claims description 3
- IZXHJFBVDXOSDL-VKAVYKQESA-N (3z)-4-(3-hydroxy-3-phenylprop-1-ynyl)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=CC=CC=4)C=CC=C3NC\2=O)=C1OC IZXHJFBVDXOSDL-VKAVYKQESA-N 0.000 claims description 3
- WPAMZQZOUUBLDX-HNMBUVAWSA-N (3z)-4-[(e)-2-(2-chlorophenyl)ethenyl]-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound ClC1=CC=CC=C1\C=C\C1=CC=CC(NC\2=O)=C1C/2=C/C1=CC=CN1 WPAMZQZOUUBLDX-HNMBUVAWSA-N 0.000 claims description 3
- IEMHQFOFIAWLHH-VAVYRGOBSA-N (3z)-4-[(e)-2-(4-methoxyphenyl)ethenyl]-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound C1=CC(OC)=CC=C1\C=C\C1=CC=CC(NC\2=O)=C1C/2=C/C1=CC=CN1 IEMHQFOFIAWLHH-VAVYRGOBSA-N 0.000 claims description 3
- DTCDOONGFRBLDF-PAAQWSFZSA-N (3z)-4-[(e)-2-(4-methoxyphenyl)ethenyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(\C=C\C=4C=CC(OC)=CC=4)C=CC=C3NC\2=O)=C1OC DTCDOONGFRBLDF-PAAQWSFZSA-N 0.000 claims description 3
- NUCZORXTPQUVGZ-VBKFSLOCSA-N (3z)-4-[3-(1,3-benzodioxol-5-yl)-3-hydroxyprop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=C5OCOC5=CC=4)C=CC=C3NC\2=O)=C1OC NUCZORXTPQUVGZ-VBKFSLOCSA-N 0.000 claims description 3
- YRXDNKVXUTYODU-SQFISAMPSA-N (3z)-4-[3-hydroxy-3-(1-methylpyrrol-2-yl)prop-1-ynyl]-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4N(C=CC=4)C)C=CC=C3NC\2=O)=C1OC YRXDNKVXUTYODU-SQFISAMPSA-N 0.000 claims description 3
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- LELVBSYVHOBCGR-PDGQHHTCSA-N (3z)-5-(2-pyridin-3-ylethynyl)-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=C(C#CC=3C=NC=CC=3)C=C2\C1=C\C1=CC=CN1 LELVBSYVHOBCGR-PDGQHHTCSA-N 0.000 claims description 3
- BGMXWZJIMIWZLP-UYRXBGFRSA-N (3z)-5-[2-(3-nitrophenyl)ethynyl]-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound [O-][N+](=O)C1=CC=CC(C#CC=2C=C3C(=C/C=4NC=CC=4)/C(=O)NC3=CC=2)=C1 BGMXWZJIMIWZLP-UYRXBGFRSA-N 0.000 claims description 3
- YRAQZUQALGLTGH-UYRXBGFRSA-N (3z)-5-[2-(4-nitrophenyl)ethynyl]-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound C1=CC([N+](=O)[O-])=CC=C1C#CC1=CC=C(NC(=O)\C2=C/C=3NC=CC=3)C2=C1 YRAQZUQALGLTGH-UYRXBGFRSA-N 0.000 claims description 3
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims description 3
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 229940095102 methyl benzoate Drugs 0.000 claims description 3
- DKNKBLBPQHSVGJ-HKWRFOASSA-N n-[(3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-2-oxo-4-(2-pyridin-3-ylethynyl)-1h-indol-5-yl]-2-thiophen-2-ylacetamide Chemical compound C1=CNC(\C=C/2C3=C(C#CC=4C=NC=CC=4)C(NC(=O)CC=4SC=CC=4)=CC=C3NC\2=O)=C1OC DKNKBLBPQHSVGJ-HKWRFOASSA-N 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
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- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- WRJUBHOADRPYQU-PGMHBOJBSA-N tert-butyl 2-[4-[1-hydroxy-3-[(3z)-3-[(3-methoxy-1h-pyrrol-2-yl)methylidene]-2-oxo-1h-indol-4-yl]prop-2-ynyl]phenoxy]acetate Chemical compound C1=CNC(\C=C/2C3=C(C#CC(O)C=4C=CC(OCC(=O)OC(C)(C)C)=CC=4)C=CC=C3NC\2=O)=C1OC WRJUBHOADRPYQU-PGMHBOJBSA-N 0.000 claims description 3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Rheumatology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11258998P | 1998-12-17 | 1998-12-17 | |
| US112589P | 1998-12-17 | ||
| US14148299P | 1999-06-29 | 1999-06-29 | |
| PCT/EP1999/009578 WO2000035906A2 (en) | 1998-12-17 | 1999-12-07 | 4- and 5-alkynyloxindoles and 4- and 5-alkenyloxindoles |
| US141482P | 2008-12-30 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69912479D1 DE69912479D1 (de) | 2003-12-04 |
| DE69912479T2 true DE69912479T2 (de) | 2004-07-22 |
Family
ID=26810125
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69912479T Expired - Fee Related DE69912479T2 (de) | 1998-12-17 | 1999-12-07 | 4- und 5-alkynyloxindole sowie 4- und 5-alkenyloxindole |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP1149092B1 (enExample) |
| JP (1) | JP2002532490A (enExample) |
| KR (1) | KR20010087421A (enExample) |
| CN (1) | CN1147486C (enExample) |
| AT (1) | ATE253062T1 (enExample) |
| AU (1) | AU771599B2 (enExample) |
| BR (1) | BR9916272A (enExample) |
| CA (1) | CA2354510A1 (enExample) |
| DE (1) | DE69912479T2 (enExample) |
| DK (1) | DK1149092T3 (enExample) |
| ES (1) | ES2209527T3 (enExample) |
| PT (1) | PT1149092E (enExample) |
| TR (1) | TR200101747T2 (enExample) |
| WO (1) | WO2000035906A2 (enExample) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6569868B2 (en) | 1998-04-16 | 2003-05-27 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
| MY128450A (en) | 2000-05-24 | 2007-02-28 | Upjohn Co | 1-(pyrrolidin-1-ylmethyl)-3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives |
| EP1294688A2 (en) | 2000-06-02 | 2003-03-26 | Sugen, Inc. | Indolinone derivatives as protein kinase/phosphatase inhibitors |
| CA2414468A1 (en) * | 2000-06-30 | 2002-01-10 | Sugen, Inc. | 4-heteroaryl-3-heteroarylidenyl-2-indolinones and their use as protein kinase inhibitors |
| AU2002255263B2 (en) | 2001-04-16 | 2006-12-14 | Eisai R&D Management Co., Ltd. | Novel 1H-indazole compound |
| US7018999B2 (en) | 2001-05-16 | 2006-03-28 | Cephalon, Inc. | Methods for the treatment and prevention of pain |
| US6599902B2 (en) | 2001-05-30 | 2003-07-29 | Sugen, Inc. | 5-aralkysufonyl-3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives as kinase inhibitors |
| ATE419247T1 (de) | 2001-07-23 | 2009-01-15 | Serono Lab | Arylsulfonamidderivate als hemmer c-jun- terminaler kinasen (jnk) |
| MXPA04002537A (es) * | 2001-10-12 | 2004-05-31 | Warner Lambert Co | Alquinos como inhibidores de metaloproteinasa de matriz. |
| US6962922B2 (en) | 2001-10-12 | 2005-11-08 | Warner-Lambert Company Llc | Alkynylated quinazoline compounds |
| DE60332215D1 (de) | 2002-02-28 | 2010-06-02 | Eisai R&D Man Co Ltd | Neue indazolverbindungen mit kondensiertem ring |
| US6747147B2 (en) | 2002-03-08 | 2004-06-08 | Warner-Lambert Company | Oxo-azabicyclic compounds |
| US6894057B2 (en) | 2002-03-08 | 2005-05-17 | Warner-Lambert Company | Oxo-azabicyclic compounds |
| IL164209A0 (en) | 2002-05-31 | 2005-12-18 | Eisai Co Ltd | Pyrazole derivatives and pharmaceutical compositions containing the same |
| CA2487948A1 (en) | 2002-06-14 | 2003-12-24 | Applied Research Systems Ars Holding N.V. | Azole methylidene cyanide derivatives and their use as protein kinase modulators |
| BRPI0415773A (pt) | 2003-10-24 | 2006-12-26 | Schering Ag | derivados de indolinona e sua aplicação no tratamento de estados de doença tais como cáncer |
| DE102004012070A1 (de) * | 2004-03-12 | 2005-09-29 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue cycloalkyl-haltige 5-Acylindolinone, deren Herstellung und deren Verwendung als Arzneimittel |
| US7803824B2 (en) | 2004-10-29 | 2010-09-28 | Alcon, Inc. | Use of inhibitors of Jun N-terminal kinases to treat glaucoma |
| US20060094753A1 (en) | 2004-10-29 | 2006-05-04 | Alcon, Inc. | Use of inhibitors of Jun N-terminal kinases for the treatment of glaucomatous retinopathy and ocular diseases |
| WO2006090698A1 (ja) * | 2005-02-22 | 2006-08-31 | Ono Pharmaceutical Co., Ltd. | キナーゼ阻害薬およびその用途 |
| KR20080044836A (ko) | 2005-07-15 | 2008-05-21 | 라보라뚜와르 세로노 에스. 에이. | 자궁내막증 치료용 jnk 억제제 |
| BRPI0613042A2 (pt) | 2005-07-15 | 2010-12-14 | Serono Lab | inibidores de jnk para o tratamento de endometriose |
| CN1939922B (zh) * | 2005-09-27 | 2010-10-13 | 天津和美生物技术有限公司 | 可抑制细胞释放肿瘤坏死因子的5H-噻吩[3,4-c]吡咯-4,6-二酮衍生物 |
| US7968572B2 (en) | 2005-10-03 | 2011-06-28 | Ono Pharmaceuticals Co., Ltd. | Nitrogen-containing heterocyclic compound and pharmaceutical application thereof |
| FR2962733B1 (fr) | 2010-07-13 | 2012-08-17 | Michelin Soc Tech | Polymere greffe par des molecules associatives azotees. |
| FR2962729B1 (fr) | 2010-07-13 | 2012-09-21 | Arkema France | Molecules porteuses de groupes associatifs |
| WO2012178015A2 (en) * | 2011-06-24 | 2012-12-27 | Zenobia Therapeutics, Inc. | Lrrk2 inhibitors |
| JP7270590B2 (ja) | 2019-11-27 | 2023-05-10 | 財團法人工業技術研究院 | 自己発電式検出送信装置 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9501567D0 (en) * | 1995-01-26 | 1995-03-15 | Pharmacia Spa | Hydrosoluble 3-arylidene-2-oxindole derivatives as tyrosine kinase inhibitors |
| GB9507298D0 (en) * | 1995-04-07 | 1995-05-31 | Pharmacia Spa | Substituted indolylmethylene-oxindale analogues as tyrosine kinase inhibitors |
| US5880141A (en) * | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
| GB9610964D0 (en) * | 1996-05-24 | 1996-07-31 | Pharmacia & Upjohn Spa | Substituted tetralylmethylen-oxindole analogues as tyrosine kinase inhibitors |
| ATE308520T1 (de) * | 1996-08-23 | 2005-11-15 | Sugen Inc | Kombinatorische bibliotheken von indolinone und verwandte produkte und verfahren zur behandlung von krankheiten |
| EP0984930B1 (en) * | 1997-05-07 | 2005-04-06 | Sugen, Inc. | 2-indolinone derivatives as modulators of protein kinase activity |
-
1999
- 1999-12-07 DE DE69912479T patent/DE69912479T2/de not_active Expired - Fee Related
- 1999-12-07 WO PCT/EP1999/009578 patent/WO2000035906A2/en not_active Ceased
- 1999-12-07 CA CA002354510A patent/CA2354510A1/en not_active Abandoned
- 1999-12-07 BR BR9916272-5A patent/BR9916272A/pt not_active IP Right Cessation
- 1999-12-07 EP EP99957341A patent/EP1149092B1/en not_active Expired - Lifetime
- 1999-12-07 AT AT99957341T patent/ATE253062T1/de not_active IP Right Cessation
- 1999-12-07 JP JP2000588166A patent/JP2002532490A/ja active Pending
- 1999-12-07 KR KR1020017007552A patent/KR20010087421A/ko not_active Ceased
- 1999-12-07 CN CNB998146994A patent/CN1147486C/zh not_active Expired - Fee Related
- 1999-12-07 PT PT99957341T patent/PT1149092E/pt unknown
- 1999-12-07 AU AU15076/00A patent/AU771599B2/en not_active Ceased
- 1999-12-07 DK DK99957341T patent/DK1149092T3/da active
- 1999-12-07 ES ES99957341T patent/ES2209527T3/es not_active Expired - Lifetime
- 1999-12-07 TR TR2001/01747T patent/TR200101747T2/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000035906A2 (en) | 2000-06-22 |
| ES2209527T3 (es) | 2004-06-16 |
| EP1149092B1 (en) | 2003-10-29 |
| WO2000035906A3 (en) | 2000-11-09 |
| CN1147486C (zh) | 2004-04-28 |
| CN1331689A (zh) | 2002-01-16 |
| DK1149092T3 (da) | 2004-02-23 |
| EP1149092A2 (en) | 2001-10-31 |
| BR9916272A (pt) | 2001-09-04 |
| AU771599B2 (en) | 2004-03-25 |
| KR20010087421A (ko) | 2001-09-15 |
| CA2354510A1 (en) | 2000-06-22 |
| DE69912479D1 (de) | 2003-12-04 |
| TR200101747T2 (tr) | 2001-11-21 |
| JP2002532490A (ja) | 2002-10-02 |
| AU1507600A (en) | 2000-07-03 |
| ATE253062T1 (de) | 2003-11-15 |
| PT1149092E (pt) | 2004-03-31 |
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| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |