ZA200502304B - Novel pyrimidineamide derivatives and the use thereof - Google Patents
Novel pyrimidineamide derivatives and the use thereof Download PDFInfo
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- ZA200502304B ZA200502304B ZA200502304A ZA200502304A ZA200502304B ZA 200502304 B ZA200502304 B ZA 200502304B ZA 200502304 A ZA200502304 A ZA 200502304A ZA 200502304 A ZA200502304 A ZA 200502304A ZA 200502304 B ZA200502304 B ZA 200502304B
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- South Africa
- Prior art keywords
- lower alkyl
- compound
- alkylene
- carbon atoms
- formula
- Prior art date
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Classifications
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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
- C07D401/02—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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Oncology (AREA)
- Ophthalmology & Optometry (AREA)
- Vascular Medicine (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0222514.2A GB0222514D0 (en) | 2002-09-27 | 2002-09-27 | Organic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200502304B true ZA200502304B (en) | 2006-04-26 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200502304A ZA200502304B (en) | 2002-09-27 | 2005-03-18 | Novel pyrimidineamide derivatives and the use thereof |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US7655669B2 (ru) |
| EP (1) | EP1546127B1 (ru) |
| JP (2) | JP4463685B2 (ru) |
| KR (2) | KR100876055B1 (ru) |
| CN (1) | CN100404528C (ru) |
| AT (1) | ATE369355T1 (ru) |
| AU (1) | AU2003270277B2 (ru) |
| BR (1) | BR0314797A (ru) |
| CA (1) | CA2499822C (ru) |
| DE (1) | DE60315479T2 (ru) |
| DK (1) | DK1546127T3 (ru) |
| EC (1) | ECSP055701A (ru) |
| ES (1) | ES2288615T3 (ru) |
| GB (1) | GB0222514D0 (ru) |
| HK (1) | HK1080459A1 (ru) |
| MX (1) | MXPA05003253A (ru) |
| NO (1) | NO20051966L (ru) |
| NZ (1) | NZ538930A (ru) |
| PL (1) | PL374443A1 (ru) |
| PT (1) | PT1546127E (ru) |
| RU (1) | RU2378267C2 (ru) |
| SI (1) | SI1546127T1 (ru) |
| WO (1) | WO2004029038A1 (ru) |
| ZA (1) | ZA200502304B (ru) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0222514D0 (en) * | 2002-09-27 | 2002-11-06 | Novartis Ag | Organic compounds |
| US7232825B2 (en) * | 2003-05-02 | 2007-06-19 | Guoqing P Chen | Phenylaminopyrimidine derivatives and methods of use |
| GB0325031D0 (en) * | 2003-10-27 | 2003-12-03 | Novartis Ag | Organic compounds |
| DE10352979A1 (de) * | 2003-11-13 | 2005-06-09 | Merck Patent Gmbh | Pyridopyrimidinone |
| TW200616974A (en) * | 2004-07-01 | 2006-06-01 | Astrazeneca Ab | Chemical compounds |
| CA2577275A1 (en) | 2004-08-31 | 2006-03-09 | Astrazeneca Ab | Quinazolinone derivatives and their use as b-raf inhibitors |
| UA94570C2 (en) | 2004-09-09 | 2011-05-25 | Натко Фарма Лимитед | Phenylaminopyrimidine derivatives as inhibitors of bcr-abl kinase |
| 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 |
| 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 |
| 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 |
| KR101325424B1 (ko) * | 2005-01-28 | 2013-11-04 | 노파르티스 아게 | Ｔｉｅ-2 키나제 활성의 조절에 반응하는 질환의 치료를위한 피리미딜아미노벤즈아미드의 용도 |
| MY146795A (en) | 2005-06-09 | 2012-09-28 | Novartis Ag | Process for the synthesis of organic compounds |
| WO2008020203A1 (en) * | 2006-08-17 | 2008-02-21 | Astrazeneca Ab | Pyridinylquinaz0linamine derivatives and their use as b-raf inhibitors |
| KR20090065512A (ko) | 2006-09-22 | 2009-06-22 | 노파르티스 아게 | Ａｂｌ 티로신 키나제 억제제에 의해 필라델피아-양성 백혈병의 치료를 최적화시키는 방법 |
| KR20120049397A (ko) * | 2006-11-03 | 2012-05-16 | 노파르티스 아게 | 단백질 키나제 억제제로서의 화합물 및 조성물 |
| US7550591B2 (en) * | 2007-05-02 | 2009-06-23 | Chemagis Ltd. | Imatinib production process |
| CN101687853A (zh) | 2007-05-04 | 2010-03-31 | Irm责任有限公司 | 作为c-kit和pdgfr激酶抑制剂的嘧啶衍生物和组合物 |
| CA2686382C (en) | 2007-05-04 | 2013-09-17 | Irm Llc | Phenylaminopyrimidine derivatives and compositions thereof as c-kit and pdgfr kinase inhibitors |
| WO2008151183A1 (en) | 2007-06-04 | 2008-12-11 | Avila Therapeutics, Inc. | Heterocyclic compounds and uses thereof |
| RU2455288C2 (ru) | 2007-08-22 | 2012-07-10 | Айрм Ллк | Соединения и композиции 5-(4-(галогеналкокси)фенил)пиримидин-2-амина в качестве ингибиторов киназ |
| EA017392B1 (ru) | 2007-08-22 | 2012-12-28 | Айрм Ллк | Производные 2-гетероариламинопиримидина в качестве ингибиторов киназ |
| US8067422B2 (en) | 2008-03-04 | 2011-11-29 | Natco Pharma Limited | Crystal form of phenylamino pyrimidine derivatives |
| 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 |
| AU2012340200B2 (en) | 2011-11-17 | 2017-10-12 | Dana-Farber Cancer Institute, Inc. | Inhibitors of c-Jun-N-Terminal Kinase (JNK) |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE135699T1 (de) | 1986-01-13 | 1996-04-15 | American Cyanamid Co | 4,5,6-substituierte 2-pyrimidinamine |
| US5215989A (en) * | 1989-12-08 | 1993-06-01 | Merck & Co., Inc. | Nitrogen-containing heterocyclic compounds as class III antiarrhythmic agents |
| US5521184A (en) * | 1992-04-03 | 1996-05-28 | Ciba-Geigy Corporation | Pyrimidine derivatives and processes for the preparation thereof |
| TW225528B (ru) | 1992-04-03 | 1994-06-21 | Ciba Geigy Ag | |
| US5516775A (en) | 1992-08-31 | 1996-05-14 | Ciba-Geigy Corporation | Further use of pyrimidine derivatives |
| AU693475B2 (en) | 1993-10-01 | 1998-07-02 | Novartis Ag | Pyrimidineamine derivatives and processes for the preparation thereof |
| US5543520A (en) | 1993-10-01 | 1996-08-06 | Ciba-Geigy Corporation | Pyrimidine derivatives |
| ITMI992711A1 (it) | 1999-12-27 | 2001-06-27 | Novartis Ag | Composti organici |
| US7087608B2 (en) | 2000-03-03 | 2006-08-08 | Robert Charles Atkins | Use of PDGF receptor tyrosine kinase inhibitors for the treatment of diabetic nephropathy |
| GB0022438D0 (en) | 2000-09-13 | 2000-11-01 | Novartis Ag | Organic Compounds |
| GB0025820D0 (en) | 2000-10-20 | 2000-12-06 | Novartis Ag | Organic compounds |
| ATE331519T1 (de) * | 2001-05-16 | 2006-07-15 | Gpc Biotech Ag | Pyridylpyrimidin-derivate als wirksame verbindungen gegen prionen-krankheiten |
| GB0222514D0 (en) * | 2002-09-27 | 2002-11-06 | Novartis Ag | Organic compounds |
| JP4579927B2 (ja) | 2003-12-23 | 2010-11-10 | コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ | 浸漬リソグラフィのための除去可能なペリクル |
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