PT1635835E - Derivados de 2-aminopiridina como inibidores da raf-quinase - Google Patents
Derivados de 2-aminopiridina como inibidores da raf-quinase Download PDFInfo
- Publication number
- PT1635835E PT1635835E PT04739809T PT04739809T PT1635835E PT 1635835 E PT1635835 E PT 1635835E PT 04739809 T PT04739809 T PT 04739809T PT 04739809 T PT04739809 T PT 04739809T PT 1635835 E PT1635835 E PT 1635835E
- Authority
- PT
- Portugal
- Prior art keywords
- phenyl
- methyl
- ylamino
- benzamide
- pyrimidin
- Prior art date
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- 102000009929 raf Kinases Human genes 0.000 title claims abstract description 30
- 108010077182 raf Kinases Proteins 0.000 title claims abstract description 30
- 229940043355 kinase inhibitor Drugs 0.000 title description 9
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 9
- 150000005006 2-aminopyrimidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 80
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 201000010099 disease Diseases 0.000 claims abstract description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 22
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 10
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims abstract description 9
- -1 6-substituted 3-pyridyl Chemical group 0.000 claims description 133
- 125000000217 alkyl group Chemical group 0.000 claims description 80
- 125000003545 alkoxy group Chemical group 0.000 claims description 55
- 125000001424 substituent group Chemical group 0.000 claims description 34
- 125000004414 alkyl thio group Chemical group 0.000 claims description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 102000043136 MAP kinase family Human genes 0.000 claims description 15
- 108091054455 MAP kinase family Proteins 0.000 claims description 15
- 230000019491 signal transduction Effects 0.000 claims description 15
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- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
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- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- VFRLDHFHWNLUHV-UHFFFAOYSA-N 3-(dimethylamino)-n-[4-methyl-3-[(4-pyrazin-2-ylpyrimidin-2-yl)amino]phenyl]benzamide Chemical compound CN(C)C1=CC=CC(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3N=CC=NC=3)C(C)=CC=2)=C1 VFRLDHFHWNLUHV-UHFFFAOYSA-N 0.000 claims description 3
- UMPHGYKQHPYJMX-UHFFFAOYSA-N n-[3-[[4-(4-methoxyphenyl)pyrimidin-2-yl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide Chemical compound C1=CC(OC)=CC=C1C1=CC=NC(NC=2C(=CC=C(NC(=O)C=3C=C(C=CC=3)C(F)(F)F)C=2)C)=N1 UMPHGYKQHPYJMX-UHFFFAOYSA-N 0.000 claims description 3
- VSVJHSJEHHMYFE-UHFFFAOYSA-N n-[4-methyl-3-[(4-phenylpyrimidin-2-yl)amino]phenyl]-3-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N=C(C=CN=2)C=2C=CC=CC=2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 VSVJHSJEHHMYFE-UHFFFAOYSA-N 0.000 claims description 3
- ZHQBCDOBZORJJD-UHFFFAOYSA-N n-[4-methyl-3-[(4-pyrazin-2-ylpyrimidin-2-yl)amino]phenyl]-3-(1,1,2,2-tetrafluoroethoxy)benzamide Chemical compound C1=C(NC=2N=C(C=CN=2)C=2N=CC=NC=2)C(C)=CC=C1NC(=O)C1=CC=CC(OC(F)(F)C(F)F)=C1 ZHQBCDOBZORJJD-UHFFFAOYSA-N 0.000 claims description 3
- CIXBPOVWYGGSOJ-UHFFFAOYSA-N n-[4-methyl-3-[(4-pyrazin-2-ylpyrimidin-2-yl)amino]phenyl]-3-(2,2,2-trifluoroethoxy)benzamide Chemical compound C1=C(NC=2N=C(C=CN=2)C=2N=CC=NC=2)C(C)=CC=C1NC(=O)C1=CC=CC(OCC(F)(F)F)=C1 CIXBPOVWYGGSOJ-UHFFFAOYSA-N 0.000 claims description 3
- JDCQEVCYOJOPLE-UHFFFAOYSA-N n-[4-methyl-3-[(4-pyrazin-2-ylpyrimidin-2-yl)amino]phenyl]-3-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N=C(C=CN=2)C=2N=CC=NC=2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 JDCQEVCYOJOPLE-UHFFFAOYSA-N 0.000 claims description 3
- LKFBMAZWIZKCPT-UHFFFAOYSA-N n-[4-methyl-3-[(4-pyrazin-2-ylpyrimidin-2-yl)amino]phenyl]-3-(trifluoromethylsulfanyl)benzamide Chemical compound C1=C(NC=2N=C(C=CN=2)C=2N=CC=NC=2)C(C)=CC=C1NC(=O)C1=CC=CC(SC(F)(F)F)=C1 LKFBMAZWIZKCPT-UHFFFAOYSA-N 0.000 claims description 3
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- RTMKRAGWCQSFLL-UHFFFAOYSA-N 3-(difluoromethoxy)-n-[4-methyl-3-[(4-pyrazin-2-ylpyrimidin-2-yl)amino]phenyl]benzamide Chemical compound C1=C(NC=2N=C(C=CN=2)C=2N=CC=NC=2)C(C)=CC=C1NC(=O)C1=CC=CC(OC(F)F)=C1 RTMKRAGWCQSFLL-UHFFFAOYSA-N 0.000 claims description 2
- UZTNBILCCYRFOX-UHFFFAOYSA-N 3-fluoro-n-[4-methyl-3-[(4-pyrazin-2-ylpyrimidin-2-yl)amino]phenyl]-5-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N=C(C=CN=2)C=2N=CC=NC=2)C(C)=CC=C1NC(=O)C1=CC(F)=CC(C(F)(F)F)=C1 UZTNBILCCYRFOX-UHFFFAOYSA-N 0.000 claims description 2
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- MQGDUEQZFXLVFP-UHFFFAOYSA-N n-[3-[[4-[6-(cyclopentylamino)pyridin-3-yl]pyrimidin-2-yl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N=C(C=CN=2)C=2C=NC(NC3CCCC3)=CC=2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 MQGDUEQZFXLVFP-UHFFFAOYSA-N 0.000 claims description 2
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- WNCGJLXTPNXQQA-UHFFFAOYSA-N n-[4-methyl-3-[[4-[6-(pyridin-4-ylamino)pyridin-3-yl]pyrimidin-2-yl]amino]phenyl]-3-(trifluoromethyl)benzamide Chemical compound C1=C(NC=2N=C(C=CN=2)C=2C=NC(NC=3C=CN=CC=3)=CC=2)C(C)=CC=C1NC(=O)C1=CC=CC(C(F)(F)F)=C1 WNCGJLXTPNXQQA-UHFFFAOYSA-N 0.000 claims description 2
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
-
- 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
- C07D403/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (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)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US47870903P | 2003-06-13 | 2003-06-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT1635835E true PT1635835E (pt) | 2010-03-17 |
Family
ID=33551850
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT04739809T PT1635835E (pt) | 2003-06-13 | 2004-06-11 | Derivados de 2-aminopiridina como inibidores da raf-quinase |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US20060293340A1 (https=) |
| EP (1) | EP1635835B1 (https=) |
| JP (1) | JP2006527230A (https=) |
| CN (1) | CN1805748B (https=) |
| AT (1) | ATE454152T1 (https=) |
| AU (1) | AU2004246800B2 (https=) |
| BR (1) | BRPI0411365A (https=) |
| CA (1) | CA2529090A1 (https=) |
| DE (1) | DE602004024988D1 (https=) |
| ES (1) | ES2338557T3 (https=) |
| MX (1) | MXPA05013349A (https=) |
| PL (1) | PL1635835T3 (https=) |
| PT (1) | PT1635835E (https=) |
| WO (1) | WO2004110452A1 (https=) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7939541B2 (en) * | 2004-09-09 | 2011-05-10 | Natco Pharma Limited | Intermediates and a process employing the intermediates for the preparation of (3-trifluoromethylsulfonyl)-N-[4-methyl-3-(4-pyridin-3yl-pyrimidin-2ylamino)-phenyl]-benzamide |
| US8735415B2 (en) | 2004-09-09 | 2014-05-27 | Natco Pharma Limited | Acid addition salts of (3,5-Bis trifluoromethyl)-N-[4-methyl-3-(4-pyridin-3yl-pyrimidin-2ylamino)-phenyl]-benzamide |
| UA94570C2 (en) * | 2004-09-09 | 2011-05-25 | Натко Фарма Лимитед | Phenylaminopyrimidine derivatives as inhibitors of bcr-abl kinase |
| CN1972917B (zh) * | 2004-12-31 | 2010-08-25 | 孙飘扬 | 氨基嘧啶类化合物及其盐和其制备方法与药物用途 |
| CN1939910A (zh) | 2004-12-31 | 2007-04-04 | 孙飘扬 | 氨基嘧啶类化合物及其盐和其制备方法与药物用途 |
| CN101160131A (zh) * | 2005-02-25 | 2008-04-09 | 诺瓦提斯公司 | Bcr-abl和raf抑制剂的药物组合产品 |
| KR100674813B1 (ko) * | 2005-08-05 | 2007-01-29 | 일양약품주식회사 | Ｎ-페닐-2-피리미딘-아민 유도체 및 그의 제조방법 |
| KR20080110998A (ko) * | 2006-01-30 | 2008-12-22 | 엑셀리시스, 인코포레이티드 | Ｊａｋ２ 조절자로서 ４아릴２아미노피리미딘 또는 4아릴２아미노알킬피리미딘 및 이들을 포함하는 약제학적 조성물 |
| US20100216791A1 (en) * | 2006-08-17 | 2010-08-26 | Astrazeneca | Pyridinylquinazolinamine derivatives and their use as b-raf inhibitors |
| BRPI0718812A2 (pt) | 2006-11-16 | 2013-12-03 | Italiana Sint Spa | Processo para a preparação de imatinib e intermediários deste |
| EP2152688A1 (en) * | 2007-05-04 | 2010-02-17 | Irm Llc | Compounds and compositions as c-kit and pdgfr kinase inhibitors |
| ES2607794T3 (es) * | 2007-06-07 | 2017-04-04 | Intra-Cellular Therapies, Inc. | Compuestos heterocíclicos novedosos y usos de los mismos |
| WO2008153959A1 (en) * | 2007-06-07 | 2008-12-18 | Intra-Cellular Therapies, Inc. | Novel heterocycle compounds and uses thereof |
| AU2008337286B2 (en) | 2007-12-19 | 2014-08-07 | Cancer Research Technology Limited | Pyrido[2,3-b]pyrazine-8-substituted compounds and their use |
| PE20091561A1 (es) * | 2008-02-29 | 2009-10-30 | Array Biopharma Inc | Compuestos inhibidores de raf y metodos para su uso |
| JP2011513331A (ja) * | 2008-02-29 | 2011-04-28 | アレイ バイオファーマ、インコーポレイテッド | ピラゾール［３，４−ｂ］ピリジンＲＡＦ阻害剤 |
| JP2011513332A (ja) * | 2008-02-29 | 2011-04-28 | アレイ バイオファーマ、インコーポレイテッド | 癌の治療のためのｒａｆ阻害剤としてのｎ−（６−アミノピリジン−３−イル）−３−（スルホンアミド）ベンズアミド誘導体 |
| ES2392482T3 (es) * | 2008-02-29 | 2012-12-11 | Array Biopharma, Inc. | Derivados de imidazo[4,5-b] piridina usados como inhibidores de RAF |
| US8067422B2 (en) | 2008-03-04 | 2011-11-29 | Natco Pharma Limited | Crystal form of phenylamino pyrimidine derivatives |
| US8513242B2 (en) | 2008-12-12 | 2013-08-20 | Cystic Fibrosis Foundation Therapeutics, Inc. | Pyrimidine compounds and methods of making and using same |
| WO2010100127A1 (en) | 2009-03-04 | 2010-09-10 | Novartis Ag | Disubstituted imidazole derivatives as modulators of raf kinase |
| SG178279A1 (en) | 2009-08-05 | 2012-03-29 | Intra Cellular Therapies Inc | Novel regulatory proteins and inhibitors |
| MX2012005332A (es) * | 2009-11-13 | 2012-10-15 | Oscotec Inc | Inhibidores de cinasa. |
| NZ601085A (en) | 2010-02-01 | 2015-04-24 | Cancer Rec Tech Ltd | 1-(5-tert-butyl-2-phenyl-2h-pyrazol-3-yl)-3-[2-fluoro-4-(1-methyl-2-oxo-2,3-dihydro-1h-imidazo[4,5-b]pyridin-7-yloxy)-phenyl]-urea and related compounds and their use in therapy |
| EP2569288A2 (en) * | 2010-05-11 | 2013-03-20 | Krisani Biosciences (P) Ltd. | 4,6-dibenzoylamino-2-methyl-pyrimidine derivatives and their use for the treatment of cancer |
| US8334292B1 (en) | 2010-06-14 | 2012-12-18 | Cystic Fibrosis Foundation Therapeutics, Inc. | Pyrimidine compounds and methods of making and using same |
| US8551479B2 (en) * | 2010-09-10 | 2013-10-08 | Oncomed Pharmaceuticals, Inc. | Methods for treating melanoma |
| CA2818544A1 (en) * | 2010-11-19 | 2012-05-24 | Glaxosmithkline Intellectual Property (No.2) Limited | Method of treatment with braf inhibitor |
| GB201320729D0 (en) | 2013-11-25 | 2014-01-08 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
| GB201320732D0 (en) | 2013-11-25 | 2014-01-08 | Cancer Rec Tech Ltd | Methods of chemical synthesis |
| WO2016172528A1 (en) * | 2015-04-23 | 2016-10-27 | Inhibikase Therapeutics, Inc. | Compositions and methods for inhibiting kinases |
| CN108586439A (zh) * | 2018-06-03 | 2018-09-28 | 刘思良 | 一种Raf激酶抑制剂及其在癌症治疗中的应用 |
| CN108864060A (zh) * | 2018-06-03 | 2018-11-23 | 刘思良 | 一种重氮类衍生物及其在癌症治疗中的应用 |
| CN108484587A (zh) * | 2018-06-03 | 2018-09-04 | 刘思良 | 一种Raf激酶抑制剂及其在癌症治疗中的应用 |
| CN108610336A (zh) * | 2018-06-03 | 2018-10-02 | 刘思良 | 一种重氮类衍生物及其在癌症治疗中的应用 |
| US11066404B2 (en) | 2018-10-11 | 2021-07-20 | Incyte Corporation | Dihydropyrido[2,3-d]pyrimidinone compounds as CDK2 inhibitors |
| WO2020168197A1 (en) | 2019-02-15 | 2020-08-20 | Incyte Corporation | Pyrrolo[2,3-d]pyrimidinone compounds as cdk2 inhibitors |
| WO2020180959A1 (en) | 2019-03-05 | 2020-09-10 | Incyte Corporation | Pyrazolyl pyrimidinylamine compounds as cdk2 inhibitors |
| WO2020205560A1 (en) | 2019-03-29 | 2020-10-08 | Incyte Corporation | Sulfonylamide compounds as cdk2 inhibitors |
| US11440914B2 (en) | 2019-05-01 | 2022-09-13 | Incyte Corporation | Tricyclic amine compounds as CDK2 inhibitors |
| WO2020223558A1 (en) | 2019-05-01 | 2020-11-05 | Incyte Corporation | Tricyclic amine compounds as cdk2 inhibitors |
| TW202115024A (zh) | 2019-08-14 | 2021-04-16 | 美商英塞特公司 | 作為cdk2 抑制劑之咪唑基嘧啶基胺化合物 |
| AU2020364007A1 (en) | 2019-10-11 | 2022-04-28 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
| US11981671B2 (en) | 2021-06-21 | 2024-05-14 | Incyte Corporation | Bicyclic pyrazolyl amines as CDK2 inhibitors |
| US11976073B2 (en) | 2021-12-10 | 2024-05-07 | Incyte Corporation | Bicyclic amines as CDK2 inhibitors |
| IL314582A (en) * | 2022-02-03 | 2024-09-01 | Nexys Therapeutics Inc | Aryl hydrocarbon receptor agonists and uses thereof |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
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| TW225528B (https=) * | 1992-04-03 | 1994-06-21 | Ciba Geigy Ag | |
| US5521184A (en) * | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
| UA71555C2 (en) * | 1997-10-06 | 2004-12-15 | Zentaris Gmbh | Methods for modulating function of serine/threonine protein kinases by 5-azaquinoline derivatives |
| GB9924092D0 (en) * | 1999-10-13 | 1999-12-15 | Zeneca Ltd | Pyrimidine derivatives |
| GB0022438D0 (en) * | 2000-09-13 | 2000-11-01 | Novartis Ag | Organic Compounds |
| AU2002342878A1 (en) * | 2001-05-16 | 2002-11-25 | Axxima Pharmaceuticals Ag | Pyridylpyrimidine derivatives as effective compounds against prion diseases |
| GB0121488D0 (en) * | 2001-09-05 | 2001-10-24 | Smithkline Beecham Plc | Compounds |
| GB0201508D0 (en) * | 2002-01-23 | 2002-03-13 | Novartis Ag | Organic compounds |
| GB0202873D0 (en) * | 2002-02-07 | 2002-03-27 | Novartis Ag | Organic compounds |
| WO2003070173A2 (en) * | 2002-02-15 | 2003-08-28 | Sympore Gmbh | Conjugates of biologically active compounds, methods for their preparation and use, formulation and pharmaceutical applications thereof |
| WO2004002963A1 (ja) * | 2002-06-28 | 2004-01-08 | Nippon Shinyaku Co., Ltd. | アミド誘導体及び医薬 |
| US7144911B2 (en) * | 2002-12-31 | 2006-12-05 | Deciphera Pharmaceuticals Llc | Anti-inflammatory medicaments |
| GB2398565A (en) * | 2003-02-18 | 2004-08-25 | Cipla Ltd | Imatinib preparation and salts |
-
2004
- 2004-06-11 AU AU2004246800A patent/AU2004246800B2/en not_active Ceased
- 2004-06-11 PL PL04739809T patent/PL1635835T3/pl unknown
- 2004-06-11 JP JP2006515898A patent/JP2006527230A/ja active Pending
- 2004-06-11 MX MXPA05013349A patent/MXPA05013349A/es active IP Right Grant
- 2004-06-11 CA CA002529090A patent/CA2529090A1/en not_active Abandoned
- 2004-06-11 AT AT04739809T patent/ATE454152T1/de not_active IP Right Cessation
- 2004-06-11 EP EP04739809A patent/EP1635835B1/en not_active Expired - Lifetime
- 2004-06-11 DE DE602004024988T patent/DE602004024988D1/de not_active Expired - Lifetime
- 2004-06-11 WO PCT/EP2004/006317 patent/WO2004110452A1/en not_active Ceased
- 2004-06-11 PT PT04739809T patent/PT1635835E/pt unknown
- 2004-06-11 CN CN2004800163287A patent/CN1805748B/zh not_active Expired - Fee Related
- 2004-06-11 US US10/560,352 patent/US20060293340A1/en not_active Abandoned
- 2004-06-11 BR BRPI0411365-9A patent/BRPI0411365A/pt not_active IP Right Cessation
- 2004-06-11 ES ES04739809T patent/ES2338557T3/es not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| AU2004246800A1 (en) | 2004-12-23 |
| CN1805748A (zh) | 2006-07-19 |
| ATE454152T1 (de) | 2010-01-15 |
| BRPI0411365A (pt) | 2006-07-25 |
| PL1635835T3 (pl) | 2010-06-30 |
| DE602004024988D1 (de) | 2010-02-25 |
| EP1635835B1 (en) | 2010-01-06 |
| US20060293340A1 (en) | 2006-12-28 |
| CN1805748B (zh) | 2010-05-26 |
| WO2004110452A1 (en) | 2004-12-23 |
| EP1635835A1 (en) | 2006-03-22 |
| AU2004246800B2 (en) | 2008-12-04 |
| JP2006527230A (ja) | 2006-11-30 |
| MXPA05013349A (es) | 2006-03-09 |
| ES2338557T3 (es) | 2010-05-10 |
| CA2529090A1 (en) | 2004-12-23 |
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