CN1871009A - 作为抗癌剂的5－芳基嘧啶 - Google Patents
作为抗癌剂的5－芳基嘧啶 Download PDFInfo
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- CN1871009A CN1871009A CNA200480031581XA CN200480031581A CN1871009A CN 1871009 A CN1871009 A CN 1871009A CN A200480031581X A CNA200480031581X A CN A200480031581XA CN 200480031581 A CN200480031581 A CN 200480031581A CN 1871009 A CN1871009 A CN 1871009A
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- Prior art keywords
- chloro
- pyrimidine
- amine
- amido
- chemical compound
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- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims description 270
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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
-
- 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
-
- 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
-
- 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
-
- 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
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
-
- 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
- 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
- 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| CN1871009A true CN1871009A (zh) | 2006-11-29 |
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| CO (1) | CO5690592A2 (enExample) |
| DE (1) | DE602004021269D1 (enExample) |
| EC (1) | ECSP066457A (enExample) |
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| IL (1) | IL174305A0 (enExample) |
| MX (1) | MXPA06003207A (enExample) |
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| PA (1) | PA8613201A1 (enExample) |
| PE (1) | PE20050470A1 (enExample) |
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| ZA (1) | ZA200602386B (enExample) |
Cited By (1)
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| CN114585618A (zh) * | 2019-11-01 | 2022-06-03 | 优迈特株式会社 | 含氟嘧啶化合物及其制造方法 |
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| TW200637556A (en) * | 2005-01-31 | 2006-11-01 | Basf Ag | Substituted 5-phenyl pyrimidines I in therapy |
| EP1891052A1 (en) * | 2005-06-13 | 2008-02-27 | Wyeth | Tubulin inhibitor and process for its preparation |
| CN101193884A (zh) | 2005-06-13 | 2008-06-04 | 惠氏公司 | 微管蛋白抑制剂和其制备方法 |
| US20110201496A1 (en) * | 2006-03-27 | 2011-08-18 | Joachim Rheinheimer | Substituted 5-Hetaryl-4-Aminopyrimidines |
| CL2007002231A1 (es) * | 2006-08-02 | 2008-04-11 | Basf Ag | Uso de compuestos derivados de 5-(het) arilpirimidina para combatir hongos daninos; compuestos derivados de 5-(het) arilpirimidina; agente fungicida; y agente farmaceutico. |
| AR064852A1 (es) * | 2007-01-11 | 2009-04-29 | Basf Ag | Pirimidinas sustituidas en posicion 2 |
| WO2009007187A1 (de) * | 2007-07-09 | 2009-01-15 | Basf Se | Substituierte 5-hetarylpyrimidine |
| PE20140502A1 (es) | 2011-04-22 | 2014-05-02 | Signal Pharm Llc | Pirimidinas sustituidas de diaminocarboxamida y diaminocarbonitrilo, composiciones de las mismas y metodos de tratamiento con las mismas |
| WO2014047257A2 (en) | 2012-09-19 | 2014-03-27 | The Trustees Of The University Of Pennsylvania | Heterocyclic compounds and their use for the treatment of neurodegenerative tauopathies |
| NZ715903A (en) | 2014-01-30 | 2017-06-30 | Signal Pharm Llc | Solid forms of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide, compositions thereof and methods of their use |
| BR112017012795A2 (pt) | 2014-12-16 | 2018-01-02 | Signal Pharmaceuticals, Llc | Formulações de 2-(terc-butilamino)-4-((1r,3r,4r)-3- hidroxi-4-metilciclo-hexilamino)-pirimidina-5- carboxamida |
| JP6903577B2 (ja) | 2014-12-16 | 2021-07-14 | シグナル ファーマシューティカルズ，エルエルシー | 皮膚におけるｃ−Ｊｕｎ Ｎ末端キナーゼの阻害の測定方法 |
| CA2975260C (en) | 2015-01-29 | 2024-05-21 | Signal Pharmaceuticals Llc | Isotopologues of 2-(tert-butylamino)-4-((1r,3r,4r)-3-hydroxy-4-methylcyclohexylamino)-pyrimidine-5-carboxamide |
| MX2018001004A (es) | 2015-07-24 | 2018-06-07 | Celgene Corp | Metodos de sintesis de clorhidrato de (1r,2r,5r)-5-amino-2-metilci clohexanol e intermedios utiles en este. |
| WO2019169111A1 (en) | 2018-03-02 | 2019-09-06 | The Trustees Of The University Of Pennsylvania | [1,2,4]triazolo[1,5-a]pyrimidine compounds and use in stabilizing microtubules |
| TW202132285A (zh) * | 2019-11-13 | 2021-09-01 | 美商愛彼特生物製藥股份有限公司 | 經取代異吲哚啉基2,2’-聯嘧啶基化合物、其類似物及使用其之方法 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US88096A (en) * | 1869-03-23 | t h a y e r | ||
| US116429A (en) * | 1871-06-27 | Improvement in dial-telegraph apparatus | ||
| US61889A (en) * | 1867-02-05 | Improvement in animal teaps | ||
| US69242A (en) * | 1867-09-24 | Calvin pepper | ||
| US147744A (en) * | 1874-02-24 | Improvement in locomotive-furnaces | ||
| GB9700664D0 (en) | 1997-01-14 | 1997-03-05 | British Tech Group | Anti-cancer agents |
| US6117876A (en) | 1997-04-14 | 2000-09-12 | American Cyanamid Company | Fungicidal trifluorophenyl-triazolopyrimidines |
| AU3536699A (en) | 1998-04-27 | 1999-11-16 | Ihara Chemical Industry Co. Ltd. | 3-arylphenyl sulfide derivatives and insecticides and miticides |
| US5986135A (en) | 1998-09-25 | 1999-11-16 | American Cyanamid Company | Fungicidal trifluoromethylalkylamino-triazolopyrimidines |
| US6156925A (en) | 1998-09-25 | 2000-12-05 | American Cyanamid Company | Process for the preparation of halogenated phenylmaloates |
| AU778913B2 (en) * | 2000-06-13 | 2004-12-23 | Basf Aktiengesellschaft | Fungicidal 5-phenyl substituted 2-(cyanoamino) pyrimidines |
| US6670362B2 (en) | 2000-09-20 | 2003-12-30 | Pfizer Inc. | Pyridazine endothelin antagonists |
| WO2002074753A2 (de) | 2001-03-15 | 2002-09-26 | Basf Aktiengesellschaft | 5-phenylpyrimidine, verfahren und zwischenprodukte zu ihrer herstellung und ihre verwendung zur bekaempfung von schadpilzen |
| DE60204509T2 (de) | 2001-04-20 | 2006-03-16 | Ciba Speciality Chemicals Holding Inc. | 4-Amino-2-(2-pyridinyl)pyrimidine als mikrobizide Wirksubstanzen |
| CN1312134C (zh) | 2001-11-19 | 2007-04-25 | 巴斯福股份公司 | 5－苯基嘧啶化合物、包含它们的组合物、其制备方法及其用途 |
| ATE428705T1 (de) | 2002-02-21 | 2009-05-15 | Basf Se | 2-(2-pyridyl)-5-phenyl-6-aminopyrimidine, verfahren und zwischenprodukte zu ihrer herstellung und ihre verwendung zur bekämpfung von schadpilzen |
| CN1642422A (zh) | 2002-03-15 | 2005-07-20 | 西巴特殊化学品控股有限公司 | 4－氨基嘧啶及其在表面抗菌处理中的应用 |
| PT2316831E (pt) | 2002-11-21 | 2013-06-06 | Novartis Ag | 2-(morfolin-4-il)pirimidinas como inibidores da fosfatidilinositol (pi) quinase e a sua utilização no tratamento do cancro |
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2004
- 2004-09-17 MX MXPA06003207A patent/MXPA06003207A/es unknown
- 2004-09-17 CA CA002539235A patent/CA2539235A1/en not_active Abandoned
- 2004-09-17 CN CNA200480031581XA patent/CN1871009A/zh active Pending
- 2004-09-17 KR KR1020067005903A patent/KR20060089215A/ko not_active Withdrawn
- 2004-09-17 RU RU2006107578/04A patent/RU2006107578A/ru not_active Application Discontinuation
- 2004-09-17 WO PCT/US2004/030682 patent/WO2005030216A1/en not_active Ceased
- 2004-09-17 EP EP04784529A patent/EP1663241B1/en not_active Expired - Lifetime
- 2004-09-17 BR BRPI0414736-7A patent/BRPI0414736A/pt not_active IP Right Cessation
- 2004-09-17 JP JP2006528086A patent/JP2007506746A/ja not_active Withdrawn
- 2004-09-17 AT AT04784529T patent/ATE432077T1/de not_active IP Right Cessation
- 2004-09-17 AU AU2004275733A patent/AU2004275733A1/en not_active Withdrawn
- 2004-09-17 DE DE602004021269T patent/DE602004021269D1/de not_active Expired - Fee Related
- 2004-09-21 TW TW093128501A patent/TW200512198A/zh unknown
- 2004-09-22 SA SA04250303A patent/SA04250303A/ar unknown
- 2004-09-22 PE PE2004000922A patent/PE20050470A1/es not_active Application Discontinuation
- 2004-09-23 GT GT200400188A patent/GT200400188A/es unknown
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- 2004-09-24 PA PA20048613201A patent/PA8613201A1/es unknown
- 2004-09-24 US US10/950,375 patent/US7524849B2/en not_active Expired - Fee Related
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2006
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- 2006-03-23 NO NO20061319A patent/NO20061319L/no not_active Application Discontinuation
- 2006-03-23 ZA ZA200602386A patent/ZA200602386B/xx unknown
- 2006-03-24 EC EC2006006457A patent/ECSP066457A/es unknown
- 2006-04-21 CO CO06038135A patent/CO5690592A2/es not_active Application Discontinuation
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114585618A (zh) * | 2019-11-01 | 2022-06-03 | 优迈特株式会社 | 含氟嘧啶化合物及其制造方法 |
| US12371422B2 (en) | 2019-11-01 | 2025-07-29 | Unimatec Co., Ltd. | Fluorine-containing pyrimidine compound and manufacturing method for same |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1663241B1 (en) | 2009-05-27 |
| AR045811A1 (es) | 2005-11-16 |
| US20050075357A1 (en) | 2005-04-07 |
| PA8613201A1 (es) | 2005-11-25 |
| BRPI0414736A (pt) | 2006-11-21 |
| TW200512198A (en) | 2005-04-01 |
| ECSP066457A (es) | 2006-09-18 |
| RU2006107578A (ru) | 2007-10-27 |
| EP1663241A1 (en) | 2006-06-07 |
| SA04250303A (ar) | 2005-12-03 |
| JP2007506746A (ja) | 2007-03-22 |
| WO2005030216A1 (en) | 2005-04-07 |
| GT200400188A (es) | 2005-05-02 |
| PE20050470A1 (es) | 2005-10-03 |
| KR20060089215A (ko) | 2006-08-08 |
| ZA200602386B (en) | 2009-03-25 |
| CO5690592A2 (es) | 2006-10-31 |
| DE602004021269D1 (de) | 2009-07-09 |
| MXPA06003207A (es) | 2006-06-23 |
| US7524849B2 (en) | 2009-04-28 |
| NO20061319L (no) | 2006-04-20 |
| CA2539235A1 (en) | 2005-04-07 |
| IL174305A0 (en) | 2008-02-09 |
| AU2004275733A1 (en) | 2005-04-07 |
| ATE432077T1 (de) | 2009-06-15 |
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