SA04250302A - 6ـفينيل(مستبدل) تريازولوبيريميدينات كعوامل مضاده للسرطان - Google Patents
6ـفينيل(مستبدل) تريازولوبيريميدينات كعوامل مضاده للسرطان Download PDFInfo
- Publication number
- SA04250302A SA04250302A SA04250302A SA04250302A SA04250302A SA 04250302 A SA04250302 A SA 04250302A SA 04250302 A SA04250302 A SA 04250302A SA 04250302 A SA04250302 A SA 04250302A SA 04250302 A SA04250302 A SA 04250302A
- Authority
- SA
- Saudi Arabia
- Prior art keywords
- pyrimidine
- triazolo
- amine
- pharmaceutically acceptable
- chloro
- Prior art date
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- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 201000002510 thyroid cancer Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- XPDWGBQVDMORPB-UHFFFAOYSA-N trifluoromethane acid Natural products FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 235000012773 waffles Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
Landscapes
- 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)
- Oncology (AREA)
- Hematology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US50554403P | 2003-09-24 | 2003-09-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SA04250302A true SA04250302A (ar) | 2005-12-03 |
Family
ID=34393032
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SA04250302A SA04250302A (ar) | 2003-09-24 | 2004-09-22 | 6ـفينيل(مستبدل) تريازولوبيريميدينات كعوامل مضاده للسرطان |
Country Status (30)
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| US (1) | US7507739B2 (https=) |
| EP (1) | EP1680425B1 (https=) |
| JP (1) | JP2007506744A (https=) |
| KR (1) | KR20060098368A (https=) |
| CN (1) | CN100519559C (https=) |
| AR (1) | AR045810A1 (https=) |
| AU (1) | AU2004276240A1 (https=) |
| BR (1) | BRPI0414700A (https=) |
| CA (1) | CA2539252A1 (https=) |
| CO (1) | CO5690598A2 (https=) |
| CR (1) | CR8288A (https=) |
| CY (1) | CY1106392T1 (https=) |
| DE (1) | DE602004004295T8 (https=) |
| DK (1) | DK1680425T3 (https=) |
| EC (1) | ECSP066458A (https=) |
| ES (1) | ES2279452T3 (https=) |
| GT (1) | GT200400190A (https=) |
| IL (1) | IL174281A0 (https=) |
| MX (1) | MXPA06003206A (https=) |
| NO (1) | NO20061318L (https=) |
| PA (1) | PA8613301A1 (https=) |
| PE (1) | PE20050433A1 (https=) |
| PL (1) | PL1680425T3 (https=) |
| PT (1) | PT1680425E (https=) |
| RU (1) | RU2006107579A (https=) |
| SA (1) | SA04250302A (https=) |
| SI (1) | SI1680425T1 (https=) |
| TW (1) | TW200512211A (https=) |
| WO (1) | WO2005030775A1 (https=) |
| ZA (1) | ZA200602387B (https=) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6255309B1 (en) * | 1999-03-19 | 2001-07-03 | American Cyanomid Co. | Fungicidal trifluoromethylalkylamino-triazolopyrimidines |
| GEP20053688B (en) * | 2000-06-30 | 2005-12-12 | Wyeth Corp | Substituted-Triazolopyrimidines as Anticancer Agents |
| ES2279452T3 (es) | 2003-09-24 | 2007-08-16 | Wyeth Holdings Corporation | 6-((sustituido)fenil)triazolopirimidinas como agentes antineoplasicos. |
| US7419982B2 (en) * | 2003-09-24 | 2008-09-02 | Wyeth Holdings Corporation | Crystalline forms of 5-chloro-6-{2,6-difluoro-4-[3-(methylamino)propoxy]phenyl}-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine salts |
| MY179926A (en) * | 2003-12-08 | 2020-11-19 | Wyeth Corp | Process for the preparation of tubulin inhibitors |
| MX2007015718A (es) * | 2005-06-13 | 2008-02-21 | Wyeth Corp | Inhibidor de tubulina y proceso para su preparacion. |
| 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 |
| WO2007000412A1 (de) * | 2005-06-27 | 2007-01-04 | Basf Aktiengesellschaft | Verfahren zur herstellung von substituierten phenylmalonestern, zwischenverbindungen sowie deren verwendung zur herstellung von 5 , 7-dihydr0xy-6- (2,4, 6-trifluorphenyl) -(1,2 , 4) triazolo (1 , 5-a) pyrimidinen |
| WO2007075465A1 (en) * | 2005-12-16 | 2007-07-05 | Wyeth | Dimers and adducts of 6-[(substituted) phenyl] triazolopyrimidines useful as anticancer agents |
| TW200730530A (en) * | 2005-12-16 | 2007-08-16 | Wyeth Corp | Lyophilized compositions of a triazolopyrimidine compound |
| CN101600350A (zh) * | 2007-01-08 | 2009-12-09 | 巴斯夫欧洲公司 | 唑并嘧啶在防治植物病原性有害真菌中的用途 |
| US9649317B2 (en) | 2012-09-19 | 2017-05-16 | The Trustees Of The University Of Pennsylvania | Heterocyclic compounds and their use for the treatment of neurodegenerative tauopathies |
| US11623927B2 (en) | 2018-03-02 | 2023-04-11 | The Trustees Of The University Of Pennsylvania | Substituted [1,2,4]triazolo[1,5-a]pyrimidines for stabilizing microtubules |
| JP7646140B2 (ja) * | 2020-04-14 | 2025-03-17 | ザ トラスティーズ オブ ザ ユニバーシティ オブ ペンシルバニア | 置換された｛１，２，４，｝トリアゾロ｛１，５－ａ｝ピリミジン化合物および微小管の安定化におけるその使用 |
| CN114369098B (zh) * | 2022-01-06 | 2023-03-10 | 苏州大学 | 一种三唑并嘧啶醇类化合物及其制备方法和应用 |
Family Cites Families (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW224044B (https=) | 1991-12-30 | 1994-05-21 | Shell Internat Res Schappej B V | |
| US5593996A (en) * | 1991-12-30 | 1997-01-14 | American Cyanamid Company | Triazolopyrimidine derivatives |
| JP2794510B2 (ja) | 1992-03-27 | 1998-09-10 | 富士写真フイルム株式会社 | ハロゲン化銀写真感光材料 |
| IL108731A (en) | 1993-03-04 | 1997-03-18 | Shell Int Research | 6, N-DISUBSTITUTED-£1, 2, 4| TRIAZOLO-£1, 5-a| PYRIMIDINE- 7-AMINE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS FUNGICIDES |
| IL108747A (en) | 1993-03-04 | 1999-03-12 | Shell Int Research | Mushroom-killing preparations containing a history of 6 metamorphoses of 5 - 7 Dihalo - 1, 2 - 4 Triazlo [A-1,5] Pyrimidine Certain such new compounds and their preparation |
| RU2147584C1 (ru) | 1995-10-27 | 2000-04-20 | Американ Цианамид Компани | Способ получения дигалоидазолопиримидинов и способ получения дигидроксиазолопиримидинов |
| US5817663A (en) | 1996-10-07 | 1998-10-06 | American Cyanamid Company | Pentafluorophenylazolopyrimidines |
| US5750766A (en) | 1997-03-18 | 1998-05-12 | American Cyanamid Company | Process for the preparation of arylmalonates |
| EP0984919B1 (en) | 1997-03-18 | 2003-01-22 | Basf Aktiengesellschaft | Process for the preparation of arylmalonates |
| TWI252231B (en) | 1997-04-14 | 2006-04-01 | American Cyanamid Co | Fungicidal trifluorophenyl-triazolopyrimidines |
| US6117876A (en) | 1997-04-14 | 2000-09-12 | American Cyanamid Company | Fungicidal trifluorophenyl-triazolopyrimidines |
| US5948783A (en) | 1997-04-14 | 1999-09-07 | American Cyanamid Company | Fungicidal trifluoromethylalkylamino-triazolopyrimidines |
| US6255309B1 (en) | 1999-03-19 | 2001-07-03 | American Cyanomid Co. | Fungicidal trifluoromethylalkylamino-triazolopyrimidines |
| TW460476B (en) | 1997-04-14 | 2001-10-21 | American Cyanamid Co | Fungicidal trifluoromethylalkylamino-triazolopyrimidines |
| US5994360A (en) | 1997-07-14 | 1999-11-30 | American Cyanamid Company | Fungicidal 5-alkyl-triazolopyrimidines |
| US6020338A (en) | 1998-02-11 | 2000-02-01 | American Cyanamid Company | Fungicidal 7-alkyl-triazolopyrimidines |
| NZ506247A (en) | 1998-02-11 | 2003-03-28 | American Cyanamid Co | Fungicidal 7-(alkyl, alkenyl, alkadienyl, cycloalkyl, cycloalkenyl or aryl)-[1,2,4]triazolo[1,5-a]pyrimidines |
| US6124301A (en) | 1998-03-17 | 2000-09-26 | American Cyanamid Company | Enhancement of the efficacy of triazolopyrimidines |
| JPH11322517A (ja) | 1998-03-17 | 1999-11-24 | American Cyanamid Co | トリアゾロピリミジン類の効力の増進 |
| US5981534A (en) | 1998-09-25 | 1999-11-09 | American Cyanamid Company | Fungicidal 6-(2,6-difluoro-4-alkoxyphenyl)-triazolopyrimidines |
| US6284762B1 (en) | 1998-03-23 | 2001-09-04 | American Cyanamid Company | Fungicidal 6-(2-halo-4-alkoxyphenyl)-triazolopyrimidines |
| DE69926119T2 (de) | 1998-03-23 | 2005-12-29 | Basf Ag | Fungizide 6-(2-halo-4-alkoxyphenyl)-triazolopyrimidine |
| US6117865A (en) | 1998-09-10 | 2000-09-12 | American Cyanamid Company | Fungicidal trifluorophenyl-triazolopyrimidines |
| US6268371B1 (en) | 1998-09-10 | 2001-07-31 | American Cyanamid Co. | Fungicidal mixtures |
| JP2000103790A (ja) | 1998-09-25 | 2000-04-11 | American Cyanamid Co | 殺菌・殺カビ性のトリハロフェニル―トリアゾロピリミジン類 |
| US6242451B1 (en) | 1998-09-25 | 2001-06-05 | Klaus-Juergen Pees | Fungicidal trihalophenyl-triazolopyrimidines |
| US6277856B1 (en) | 1998-09-25 | 2001-08-21 | American Cynamid Co. | Fungicidal mixtures |
| ATE240648T1 (de) | 1998-09-25 | 2003-06-15 | Basf Ag | Fungizide mischungen |
| SK3662001A3 (en) | 1998-09-25 | 2001-11-06 | Basf Ag | Non-aqueous suspension concentrate |
| US5985883A (en) | 1998-09-25 | 1999-11-16 | American Cyanamid Company | Fungicidal trichlorophenyl-triazolopyrimidines |
| US5986135A (en) | 1998-09-25 | 1999-11-16 | American Cyanamid Company | Fungicidal trifluoromethylalkylamino-triazolopyrimidines |
| US6521628B1 (en) | 1999-01-29 | 2003-02-18 | Basf Aktiengesellschaft | Fungicidal mixtures |
| US6699874B2 (en) | 1999-09-24 | 2004-03-02 | Basf Aktiengesellschaft | Fungicidal mixtures |
| AU3154601A (en) | 1999-11-18 | 2001-05-30 | Basf Aktiengesellschaft | Non-aqueous concentrated spreading oil composition |
| US6559151B2 (en) | 2000-05-08 | 2003-05-06 | Basf Aktiengesellschaft | 6-(2-trifluoromethyl-phenyl)-triazolopyrimidines |
| GEP20053688B (en) * | 2000-06-30 | 2005-12-12 | Wyeth Corp | Substituted-Triazolopyrimidines as Anticancer Agents |
| AU1495802A (en) | 2000-08-25 | 2002-03-04 | Basf Ag | Fungicidal formulation |
| US6459602B1 (en) * | 2000-10-26 | 2002-10-01 | O2 Micro International Limited | DC-to-DC converter with improved transient response |
| JP2004513170A (ja) | 2000-11-13 | 2004-04-30 | ビーエーエスエフ アクチェンゲゼルシャフト | ７−（ｒ）−アミノトリアゾロピリミジン類、それらの製造及び植物病原性真菌を防除するためのそれらの使用 |
| DK1341794T3 (da) | 2000-12-06 | 2004-12-06 | Wyeth Corp | Fungicide 6-(2-trifluormethyl-phenyl)-triazolopyrimidiner |
| DE10063115A1 (de) | 2000-12-18 | 2002-06-27 | Bayer Ag | Triazolopyrimidine |
| WO2002067679A1 (en) | 2001-02-19 | 2002-09-06 | Basf Aktiengesellschaft | Fungicidal mixtures |
| PL367107A1 (en) | 2001-04-11 | 2005-02-21 | Basf Aktiengesellschaft | 5-halogen-6-phenyl-7-fluoroalkylamino-triazolopyrimidines as fungicides |
| DE10124208A1 (de) | 2001-05-18 | 2002-11-21 | Bayer Ag | Verwendung von Triazolopyrimidin-Derivaten als Mikrobizide |
| WO2003008416A1 (en) | 2001-07-18 | 2003-01-30 | Basf Aktiengesellschaft | Substituted 6-(2-methoxyphenyl) triazolopyrimides as fungicides |
| ES2279452T3 (es) | 2003-09-24 | 2007-08-16 | Wyeth Holdings Corporation | 6-((sustituido)fenil)triazolopirimidinas como agentes antineoplasicos. |
-
2004
- 2004-09-17 ES ES04788820T patent/ES2279452T3/es not_active Expired - Lifetime
- 2004-09-17 EP EP04788820A patent/EP1680425B1/en not_active Expired - Lifetime
- 2004-09-17 CA CA002539252A patent/CA2539252A1/en not_active Abandoned
- 2004-09-17 PL PL04788820T patent/PL1680425T3/pl unknown
- 2004-09-17 CN CNB2004800302006A patent/CN100519559C/zh not_active Expired - Fee Related
- 2004-09-17 MX MXPA06003206A patent/MXPA06003206A/es active IP Right Grant
- 2004-09-17 AU AU2004276240A patent/AU2004276240A1/en not_active Withdrawn
- 2004-09-17 DE DE602004004295T patent/DE602004004295T8/de active Active
- 2004-09-17 JP JP2006528075A patent/JP2007506744A/ja not_active Withdrawn
- 2004-09-17 BR BRPI0414700-6A patent/BRPI0414700A/pt not_active IP Right Cessation
- 2004-09-17 WO PCT/US2004/030515 patent/WO2005030775A1/en not_active Ceased
- 2004-09-17 KR KR1020067005785A patent/KR20060098368A/ko not_active Withdrawn
- 2004-09-17 RU RU2006107579/04A patent/RU2006107579A/ru not_active Application Discontinuation
- 2004-09-17 SI SI200430195T patent/SI1680425T1/sl unknown
- 2004-09-17 PT PT04788820T patent/PT1680425E/pt unknown
- 2004-09-17 DK DK04788820T patent/DK1680425T3/da active
- 2004-09-21 TW TW093128500A patent/TW200512211A/zh unknown
- 2004-09-22 SA SA04250302A patent/SA04250302A/ar unknown
- 2004-09-23 AR ARP040103440A patent/AR045810A1/es not_active Application Discontinuation
- 2004-09-23 PE PE2004000925A patent/PE20050433A1/es not_active Application Discontinuation
- 2004-09-24 GT GT200400190A patent/GT200400190A/es unknown
- 2004-09-24 PA PA20048613301A patent/PA8613301A1/es unknown
- 2004-09-24 US US10/950,543 patent/US7507739B2/en not_active Expired - Fee Related
-
2006
- 2006-03-13 IL IL174281A patent/IL174281A0/en unknown
- 2006-03-14 CR CR8288A patent/CR8288A/es not_active Application Discontinuation
- 2006-03-23 NO NO20061318A patent/NO20061318L/no not_active Application Discontinuation
- 2006-03-23 ZA ZA200602387A patent/ZA200602387B/xx unknown
- 2006-03-24 EC EC2006006458A patent/ECSP066458A/es unknown
- 2006-04-21 CO CO06038133A patent/CO5690598A2/es not_active Application Discontinuation
-
2007
- 2007-03-16 CY CY20071100373T patent/CY1106392T1/el unknown
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