BRPI0718895A2 - Composto de sulfoximina e uso do referido composto - Google Patents
Composto de sulfoximina e uso do referido composto Download PDFInfo
- Publication number
- BRPI0718895A2 BRPI0718895A2 BRPI0718895-1A BRPI0718895A BRPI0718895A2 BR PI0718895 A2 BRPI0718895 A2 BR PI0718895A2 BR PI0718895 A BRPI0718895 A BR PI0718895A BR PI0718895 A2 BRPI0718895 A2 BR PI0718895A2
- Authority
- BR
- Brazil
- Prior art keywords
- methyl
- phenyl
- sulfanylidene
- oxo
- ethynyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 257
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims abstract description 23
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims abstract description 23
- 230000019491 signal transduction Effects 0.000 claims abstract description 21
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- -1 hydroxy, hydroxymethyl Chemical group 0.000 claims description 557
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 484
- 239000011570 nicotinamide Substances 0.000 claims description 404
- 229960003966 nicotinamide Drugs 0.000 claims description 404
- 235000005152 nicotinamide Nutrition 0.000 claims description 402
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 284
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 212
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 175
- 239000000203 mixture Substances 0.000 claims description 96
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 88
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 62
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 37
- 125000000217 alkyl group Chemical group 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
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- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical group 0.000 claims description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 208000035475 disorder Diseases 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 125000002837 carbocyclic group Chemical group 0.000 claims description 10
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- 201000011510 cancer Diseases 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
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- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 7
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- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 208000030159 metabolic disease Diseases 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
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- 206010038933 Retinopathy of prematurity Diseases 0.000 claims description 3
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- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 2
- 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 2
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- 210000003584 mesangial cell Anatomy 0.000 claims description 2
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 2
- 229940002612 prodrug Drugs 0.000 claims description 2
- 239000000651 prodrug Substances 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
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- 150000002431 hydrogen Chemical group 0.000 claims 9
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 claims 2
- 206010063209 Chronic allograft nephropathy Diseases 0.000 claims 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims 1
- 206010018364 Glomerulonephritis Diseases 0.000 claims 1
- 102000004278 Receptor Protein-Tyrosine Kinases Human genes 0.000 claims 1
- 108090000873 Receptor Protein-Tyrosine Kinases Proteins 0.000 claims 1
- 208000034841 Thrombotic Microangiopathies Diseases 0.000 claims 1
- 208000033679 diabetic kidney disease Diseases 0.000 claims 1
- 230000003211 malignant effect Effects 0.000 claims 1
- 201000009925 nephrosclerosis Diseases 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 230000004663 cell proliferation Effects 0.000 abstract description 7
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 387
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- 239000000243 solution Substances 0.000 description 141
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- ZGJXAIOPBAMFSE-UHFFFAOYSA-N tert-butyl n-(4-ethynylphenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(C#C)C=C1 ZGJXAIOPBAMFSE-UHFFFAOYSA-N 0.000 description 1
- IFVHTFPRYMXLGC-UHFFFAOYSA-N tert-butyl-dimethyl-[(4-methylsulfanylphenyl)methoxy]silane Chemical compound CSC1=CC=C(CO[Si](C)(C)C(C)(C)C)C=C1 IFVHTFPRYMXLGC-UHFFFAOYSA-N 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- QIQITDHWZYEEPA-UHFFFAOYSA-N thiophene-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=CS1 QIQITDHWZYEEPA-UHFFFAOYSA-N 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000004953 trihalomethyl group Chemical group 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 210000003606 umbilical vein Anatomy 0.000 description 1
- 238000009424 underpinning Methods 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
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- 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
- C07D213/60—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 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
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- 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
- C07D401/02—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 two hetero rings
- C07D401/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- 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
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- 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
- C07D405/02—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 two hetero rings
- C07D405/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D413/06—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 linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
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- Cardiology (AREA)
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- Physical Education & Sports Medicine (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US86608006P | 2006-11-16 | 2006-11-16 | |
| US60/866,080 | 2006-11-16 | ||
| PCT/US2007/084999 WO2008061236A2 (en) | 2006-11-16 | 2007-11-16 | Sulfoximines as kinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
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| BRPI0718895A2 true BRPI0718895A2 (pt) | 2013-12-10 |
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| Application Number | Title | Priority Date | Filing Date |
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| BRPI0718895-1A BRPI0718895A2 (pt) | 2006-11-16 | 2007-11-16 | Composto de sulfoximina e uso do referido composto |
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| US (1) | US7915443B2 (enExample) |
| EP (1) | EP2099757B1 (enExample) |
| JP (1) | JP2010510242A (enExample) |
| AU (1) | AU2007319151B2 (enExample) |
| BR (1) | BRPI0718895A2 (enExample) |
| CA (1) | CA2669704A1 (enExample) |
| WO (1) | WO2008061236A2 (enExample) |
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| US7456476B2 (en) | 2003-06-27 | 2008-11-25 | Intel Corporation | Nonplanar semiconductor device with partially or fully wrapped around gate electrode and methods of fabrication |
| US8455656B2 (en) | 2004-04-30 | 2013-06-04 | Allergan, Inc. | Kinase inhibitors |
| WO2005107708A1 (en) | 2004-04-30 | 2005-11-17 | Allergan, Inc. | Biodegradable intravitreal tyrosine kinase inhibitors implants |
| US7771742B2 (en) | 2004-04-30 | 2010-08-10 | Allergan, Inc. | Sustained release intraocular implants containing tyrosine kinase inhibitors and related methods |
| US7042009B2 (en) | 2004-06-30 | 2006-05-09 | Intel Corporation | High mobility tri-gate devices and methods of fabrication |
| US20060086977A1 (en) | 2004-10-25 | 2006-04-27 | Uday Shah | Nonplanar device with thinned lower body portion and method of fabrication |
| US7518196B2 (en) | 2005-02-23 | 2009-04-14 | Intel Corporation | Field effect transistor with narrow bandgap source and drain regions and method of fabrication |
| US7858481B2 (en) | 2005-06-15 | 2010-12-28 | Intel Corporation | Method for fabricating transistor with thinned channel |
| US7547637B2 (en) | 2005-06-21 | 2009-06-16 | Intel Corporation | Methods for patterning a semiconductor film |
| US7279375B2 (en) * | 2005-06-30 | 2007-10-09 | Intel Corporation | Block contact architectures for nanoscale channel transistors |
| US20070090416A1 (en) | 2005-09-28 | 2007-04-26 | Doyle Brian S | CMOS devices with a single work function gate electrode and method of fabrication |
| US7485503B2 (en) | 2005-11-30 | 2009-02-03 | Intel Corporation | Dielectric interface for group III-V semiconductor device |
| WO2007087419A2 (en) | 2006-01-24 | 2007-08-02 | Allergan, Inc. | Substituted 3-(5-membered unsaturated heterocyclyl) -1, 3-dihydro-indol-2-one derivatives as tyrosine kinase inhibitors for the treatment of cancer |
| US8143646B2 (en) | 2006-08-02 | 2012-03-27 | Intel Corporation | Stacking fault and twin blocking barrier for integrating III-V on Si |
| US8558002B2 (en) * | 2006-11-16 | 2013-10-15 | Allergan, Inc. | Sulfoximines as kinase inhibitors |
| US8143410B2 (en) * | 2006-11-16 | 2012-03-27 | Allergan, Inc. | Kinase inhibitors |
| US8642067B2 (en) * | 2007-04-02 | 2014-02-04 | Allergen, Inc. | Methods and compositions for intraocular administration to treat ocular conditions |
| US8362566B2 (en) | 2008-06-23 | 2013-01-29 | Intel Corporation | Stress in trigate devices using complimentary gate fill materials |
| AR076332A1 (es) * | 2009-04-21 | 2011-06-01 | Boehringer Ingelheim Int | Derivados heterociclicos de 5-alquinil-piridinas, composiciones farmaceuticas que los comprenden y uso de los mismos para el tratamiento y/o prevencion del cancer, procesos inflamatorios, autoinmunes, y/o infecciones. |
| US20100278897A1 (en) * | 2009-05-01 | 2010-11-04 | Allergan, Inc. | Intraocular bioactive agent delivery system with molecular partitioning system |
| KR20160096174A (ko) * | 2013-12-12 | 2016-08-12 | 알러간, 인코포레이티드 | 키나제 저해제로서의 치환된 다이알킬(옥사이도)-λ⁴-설판일리덴 니코틴아마이드 유도체 |
| CN105814021B (zh) * | 2013-12-12 | 2020-03-13 | 阿勒根公司 | 作为激酶抑制剂的取代的烟酰胺衍生物 |
| CN111662227B (zh) * | 2019-03-06 | 2022-07-05 | 中国科学院上海药物研究所 | 邻氨基吡啶炔类化合物及其制备方法和用途 |
Family Cites Families (50)
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| US2383874A (en) * | 1941-04-24 | 1945-08-28 | Swiss Firm Of J R Geigy A G | p-aminobenzenesulphonamides and a process for their manufacture |
| GB602558A (en) * | 1945-10-24 | 1948-05-28 | Geigy Ag J R | Manufacture of aromatic acyl-sulphonamides |
| DE821977C (de) * | 1949-10-02 | 1951-11-22 | Basf Ag | Verfahren zur Herstellung von Azofarbstoffen |
| ZA804076B (en) * | 1979-07-18 | 1981-06-24 | Ici Ltd | Herbicides |
| EP0075377A3 (en) * | 1979-07-18 | 1983-08-31 | Imperial Chemical Industries Plc | Diphenyl ether compounds, their use as herbicides, and herbicidal compositions containing them |
| GB2061914A (en) * | 1979-11-01 | 1981-05-20 | American Cyanamid Co | Substituted anilines and their use as anti-atherosclerotic agents |
| JPS5998056A (ja) * | 1982-11-04 | 1984-06-06 | エフ・ホフマン−ラ・ロシユ・ウント・コンパニ−・アクチエンゲゼルシヤフト | 除草活性を有する安息香酸誘導体 |
| EP0109575A3 (de) | 1982-11-04 | 1984-09-05 | F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft | Benzoesäurederivate, Verfahren und Mittel zu deren Herstellung |
| JPS5890555A (ja) * | 1982-11-22 | 1983-05-30 | Ishihara Sangyo Kaisha Ltd | ベンズアミド誘導体及びそれらを含有する除草剤 |
| JPS6216465A (ja) * | 1985-03-14 | 1987-01-24 | Nissan Chem Ind Ltd | ベンズアミド誘導体、その製法および土壌病害防除剤 |
| US4966849A (en) | 1985-09-20 | 1990-10-30 | President And Fellows Of Harvard College | CDNA and genes for human angiogenin (angiogenesis factor) and methods of expression |
| DE3867401D1 (de) * | 1987-03-18 | 1992-02-13 | American Home Prod | Sulfonylcarboxamide. |
| US4826990A (en) * | 1987-09-30 | 1989-05-02 | American Home Products Corporation | 2-aryl substituted heterocyclic compounds as antiallergic and antiinflammatory agents |
| US5217999A (en) | 1987-12-24 | 1993-06-08 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Styryl compounds which inhibit EGF receptor protein tyrosine kinase |
| ES2064101T3 (es) | 1990-04-02 | 1995-01-16 | Pfizer | Compuestos de acido bencilfosfonico inhibidores de la quinasa de tirosina. |
| US5302606A (en) | 1990-04-16 | 1994-04-12 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Styryl-substituted pyridyl compounds which inhibit EGF receptor tyrosine kinase |
| WO1992020642A1 (en) | 1991-05-10 | 1992-11-26 | Rhone-Poulenc Rorer International (Holdings) Inc. | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit egf and/or pdgf receptor tyrosine kinase |
| CA2068355A1 (en) * | 1991-05-14 | 1992-11-15 | Mark S. Chambers | Benzodiazephine derivatives, compositions containing them and their use in therapy |
| JPH06503095A (ja) | 1991-05-29 | 1994-04-07 | ファイザー・インコーポレーテッド | 三環式ポリヒドロキシ系のチロシンキナーゼ阻害薬 |
| JP2600644B2 (ja) * | 1991-08-16 | 1997-04-16 | 藤沢薬品工業株式会社 | チアゾリルベンゾフラン誘導体 |
| JPH05294930A (ja) * | 1992-04-21 | 1993-11-09 | Yoshitomi Pharmaceut Ind Ltd | スチリル化合物 |
| JPH08503450A (ja) | 1992-08-06 | 1996-04-16 | ワーナー−ランバート・コンパニー | 蛋白チロシンキナーゼを阻害し、かつ抗腫瘍特性を有する2−チオインドール(セレノインドール)および関連ジスルフィド(セレニド) |
| US5330992A (en) | 1992-10-23 | 1994-07-19 | Sterling Winthrop Inc. | 1-cyclopropyl-4-pyridyl-quinolinones |
| AU687727B2 (en) | 1992-10-28 | 1998-03-05 | Genentech Inc. | Vascular endothelial cell growth factor antagonists |
| GB9226855D0 (en) | 1992-12-23 | 1993-02-17 | Erba Carlo Spa | Vinylene-azaindole derivatives and process for their preparation |
| DE4410453A1 (de) * | 1994-03-25 | 1995-09-28 | Hoechst Ag | Substituierte heterocyclische Carbonsäureamidester, ihre Herstellung und ihre Verwendung als Arzneimittel |
| EP0807105B1 (en) * | 1994-10-27 | 2004-06-16 | Fujisawa Pharmaceutical Co., Ltd. | Pyridopyrimidones, quinolines and fused n-heretocycles as bradykinin antagonists |
| US5880141A (en) | 1995-06-07 | 1999-03-09 | Sugen, Inc. | Benzylidene-Z-indoline compounds for the treatment of disease |
| IL124969A (en) * | 1995-12-28 | 2002-09-12 | Fujisawa Pharmaceutical Co | History of benzimidazole, processes for their preparation and pharmaceutical preparations containing them |
| WO1998056757A1 (fr) * | 1997-06-11 | 1998-12-17 | Sankyo Company, Limited | Derives de benzylamine |
| DE69926148D1 (en) | 1998-11-09 | 2005-08-18 | Black James Foundation | Gastrin und cholecystokinin rezeptor ligande |
| MXPA02009313A (es) * | 2000-03-22 | 2005-04-19 | Bayer Cropscience Gmbh | Acilsulfimidas heterociclicas, un metodo para su produccion, agentes que contienen las mismas y su uso como plaguicidas. |
| DE10021246A1 (de) * | 2000-04-25 | 2001-10-31 | Schering Ag | Substituierte Benzoesäureamide und deren Verwendung als Arzneimittel |
| US20020054093A1 (en) | 2000-10-04 | 2002-05-09 | Gonzalez Emmanuel C. | Ergonomic graphic interface for webpages, internet browsers and computers |
| JP2002205464A (ja) * | 2000-11-10 | 2002-07-23 | Oji Paper Co Ltd | 感熱記録体 |
| ES2257461T3 (es) * | 2000-12-21 | 2006-08-01 | Bristol-Myers Squibb Company | Inhibidores de tiazolilo de tirosina quinasas de la familia tec. |
| WO2004014300A2 (en) * | 2002-08-09 | 2004-02-19 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| DE10349423A1 (de) * | 2003-10-16 | 2005-06-16 | Schering Ag | Sulfoximinsubstituierte Parimidine als CDK- und/oder VEGF-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel |
| WO2005108370A1 (ja) * | 2004-04-16 | 2005-11-17 | Ajinomoto Co., Inc. | ベンゼン化合物 |
| DE102004031323A1 (de) * | 2004-06-29 | 2006-01-19 | Bayer Cropscience Ag | Substituierte Pyridazincarboxamide und Derivate hiervon |
| WO2006013449A1 (en) | 2004-07-30 | 2006-02-09 | Adriaan Francois Roberts | A swimming pool installation and accessory |
| US7776869B2 (en) | 2004-10-18 | 2010-08-17 | Amgen Inc. | Heteroaryl-substituted alkyne compounds and method of use |
| US20100048543A1 (en) | 2005-02-01 | 2010-02-25 | Astrazeneca Ab | Pyrimidine compounds having ties (tek) inhibitory activity |
| GB0502418D0 (en) | 2005-02-05 | 2005-03-16 | Astrazeneca Ab | Compounds |
| JP5081807B2 (ja) * | 2005-03-16 | 2012-11-28 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | 補体−媒介疾患及び状態の処置のための新規なチオフェンスルホキシイミン |
| EP1705177A1 (en) * | 2005-03-23 | 2006-09-27 | Schering Aktiengesellschaft | N-aryl-sulfoximine-substituted pyrimidines as CDK- and/or VEGF inhibitors, their production and use as pharmaceutical agents |
| US20080194552A1 (en) * | 2005-03-31 | 2008-08-14 | Astrazeneca Ab | Aminopyrimidine Derivatives With Tie2 Inhibiting Activity |
| ES2761180T3 (es) | 2005-12-23 | 2020-05-19 | Ariad Pharma Inc | Compuestos bicíclicos de heteroarilo |
| DE102006041382A1 (de) * | 2006-08-29 | 2008-03-20 | Bayer Schering Pharma Ag | Carbamoyl-Sulfoximide als Proteinkinaseinhibitoren |
| TW200930369A (en) * | 2007-11-15 | 2009-07-16 | Astrazeneca Ab | Bis-(sulfonylamino) derivatives in therapy |
-
2007
- 2007-11-16 US US11/941,753 patent/US7915443B2/en active Active
- 2007-11-16 JP JP2009537394A patent/JP2010510242A/ja active Pending
- 2007-11-16 AU AU2007319151A patent/AU2007319151B2/en not_active Ceased
- 2007-11-16 BR BRPI0718895-1A patent/BRPI0718895A2/pt not_active IP Right Cessation
- 2007-11-16 CA CA002669704A patent/CA2669704A1/en not_active Abandoned
- 2007-11-16 EP EP07864544.7A patent/EP2099757B1/en not_active Not-in-force
- 2007-11-16 WO PCT/US2007/084999 patent/WO2008061236A2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| EP2099757A2 (en) | 2009-09-16 |
| JP2010510242A (ja) | 2010-04-02 |
| HK1134674A1 (en) | 2010-05-07 |
| WO2008061236A3 (en) | 2008-07-31 |
| US7915443B2 (en) | 2011-03-29 |
| US20090099181A1 (en) | 2009-04-16 |
| AU2007319151B2 (en) | 2013-05-23 |
| AU2007319151A1 (en) | 2008-05-22 |
| EP2099757B1 (en) | 2014-06-25 |
| WO2008061236A2 (en) | 2008-05-22 |
| CA2669704A1 (en) | 2008-05-22 |
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