CN1379668A - 3(5)－脲基－吡唑衍生物、其制备方法及其作为抗肿瘤剂的用途 - Google Patents
3(5)－脲基－吡唑衍生物、其制备方法及其作为抗肿瘤剂的用途 Download PDFInfo
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- CN1379668A CN1379668A CN00812736A CN00812736A CN1379668A CN 1379668 A CN1379668 A CN 1379668A CN 00812736 A CN00812736 A CN 00812736A CN 00812736 A CN00812736 A CN 00812736A CN 1379668 A CN1379668 A CN 1379668A
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- pyrazoles
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| US09/372,833 US6387900B1 (en) | 1999-08-12 | 1999-08-12 | 3(5)-ureido-pyrazole derivatives process for their preparation and their use as antitumor agents |
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Families Citing this family (66)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20070244120A1 (en) * | 2000-08-18 | 2007-10-18 | Jacques Dumas | Inhibition of raf kinase using substituted heterocyclic ureas |
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| AU2003256755A1 (en) | 2002-07-24 | 2004-02-09 | Ptc Therapeutics, Inc. | Ureido substituted benzoic acid compounds, their use for nonsense suppression and the treatment of diseases caused by such mutations |
| JP2005538152A (ja) * | 2002-09-05 | 2005-12-15 | ニューロサーチ、アクティーゼルスカブ | ジアリール誘導体及びこれをクロライドチャネル遮断剤として使用する方法 |
| CA2501799C (en) | 2002-10-09 | 2008-06-17 | Pfizer Products Inc. | Pyrazole compounds for treatment of neurodegenerative disorders |
| UA81790C2 (uk) | 2002-12-19 | 2008-02-11 | Фармация Италия С.П.А. | Заміщені піролопіразольні похідні як інгібітори кінази |
| US7557129B2 (en) | 2003-02-28 | 2009-07-07 | Bayer Healthcare Llc | Cyanopyridine derivatives useful in the treatment of cancer and other disorders |
| GB0305426D0 (en) * | 2003-03-08 | 2003-04-16 | Glaxo Group Ltd | Novel compounds |
| JP2007511203A (ja) | 2003-05-20 | 2007-05-10 | バイエル、ファーマシューテイカルズ、コーポレイション | キナーゼ阻害活性を有するジアリール尿素 |
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| US7141568B2 (en) | 2003-07-09 | 2006-11-28 | Pfizer Italia S.R.L. | Pyrrolo[3,4-c]pyrazole derivatives active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them |
| DE602004010407T2 (de) | 2003-07-23 | 2008-10-16 | Bayer Pharmaceuticals Corp., West Haven | Fluorsubstituierter omega-carboxyaryldiphenylharnstoff zur behandlung und prävention von krankheiten und leiden |
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| CL2008000119A1 (es) | 2007-01-16 | 2008-05-16 | Wyeth Corp | Compuestos derivados de pirazol, antagonistas del receptor nicotinico de acetilcolina; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como demencia senil, alzheimer y esquizofrenia. |
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| US20090062294A1 (en) * | 2007-05-25 | 2009-03-05 | Richard Apodaca | Heteroaryl-substituted urea modulators of fatty acid amide hydrolase |
| EP2163541A1 (en) * | 2008-09-12 | 2010-03-17 | Bayer Schering Pharma Aktiengesellschaft | Piperazine derivatives for binding and imaging amyloid plaques and their use |
| WO2010068452A1 (en) * | 2008-11-25 | 2010-06-17 | Janssen Pharmaceutica Nv | Heteroaryl-substituted urea modulators of fatty acid amide hydrolase |
| US8461159B2 (en) | 2008-11-25 | 2013-06-11 | Jannsen Pharmaceutica BV | Heteroaryl-substituted urea modulators of fatty acid amide hydrolase |
| US20120083476A1 (en) | 2009-06-05 | 2012-04-05 | Janssen Pharmaceutica Nv | Heteroaryl-substituted spirocyclic diamine urea modulators of fatty acid amide hydrolase |
| WO2010141809A1 (en) | 2009-06-05 | 2010-12-09 | Janssen Pharmaceutica Nv | Aryl-substituted heterocyclic urea modulators of fatty acid amide hydrolase |
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| WO2012003476A2 (en) * | 2010-07-02 | 2012-01-05 | Ventana Medical Systems, Inc. | Hapten conjugates for target detection |
| CA2806634A1 (en) * | 2010-08-20 | 2012-02-23 | Gruenenthal Gmbh | Substituted cyclic carboxamide and urea derivatives as ligands of the vanilloid receptor |
| CN103119035B (zh) | 2010-09-27 | 2015-09-30 | 雅培股份有限两合公司 | 杂环化合物和它们作为糖原合成酶激酶-3抑制剂的用途 |
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| US9090592B2 (en) | 2010-12-30 | 2015-07-28 | AbbVie Deutschland GmbH & Co. KG | Heterocyclic compounds and their use as glycogen synthase kinase-3 inhibitors |
| RU2606131C2 (ru) | 2011-05-13 | 2017-01-10 | Эррэй Биофарма Инк. | СОЕДИНЕНИЯ ПИРРОЛИДИНИЛМОЧЕВИНЫ И ПИРРОЛИДИНИЛТИОМОЧЕВИНЫ КАК ИНГИБИТОРЫ КИНАЗЫ TrkA |
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| RS57001B1 (sr) | 2012-11-13 | 2018-05-31 | Array Biopharma Inc | Jedinjenja n-pirolidinil, n'-pirazolil- uree, tiouree, guanidina i cijanoguanidina kao inhibitori trka kinaze |
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| UA117573C2 (uk) | 2012-11-13 | 2018-08-27 | Ерей Біофарма Інк. | Біциклічні сполуки сечовини, тіосечовини, гуанідину й ціаногуанідину, придатні для лікування болю |
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| US9828360B2 (en) | 2012-11-13 | 2017-11-28 | Array Biopharma Inc. | Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors |
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Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3646059A (en) * | 1969-05-05 | 1972-02-29 | Du Pont | Plant growth regulatory ureidopyrazoles |
| US3754887A (en) * | 1969-05-05 | 1973-08-28 | Du Pont | Ureidopyrazoles defoliants |
| CA2203517A1 (en) | 1994-11-10 | 1996-05-23 | Alan M. Laibelman | Pharmaceutical pyrazole compositions useful as inhibitors of protein kinases |
| US6043246A (en) | 1996-12-03 | 2000-03-28 | Banyu Pharmaceutical Co., Ltd. | Urea derivatives |
| US6087381A (en) | 1997-05-22 | 2000-07-11 | G. D. Searle & Company | Pyrazole derivatives as p38 kinase inhibitors |
| JP4403482B2 (ja) | 1997-12-22 | 2010-01-27 | バイエル コーポレイション | 置換複素環尿素合成のための中間体およびその製造方法 |
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2000
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- 2000-08-10 CO CO00059913A patent/CO5200848A1/es not_active Application Discontinuation
- 2000-08-11 CN CN00812736A patent/CN1379668A/zh active Pending
- 2000-08-11 KR KR1020027001815A patent/KR20020060158A/ko not_active Application Discontinuation
- 2000-08-11 ES ES00955241T patent/ES2284518T3/es not_active Expired - Lifetime
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Also Published As
| Publication number | Publication date |
|---|---|
| JP2003507328A (ja) | 2003-02-25 |
| EP1202734A4 (en) | 2004-09-01 |
| ES2284518T3 (es) | 2007-11-16 |
| ATE361070T1 (de) | 2007-05-15 |
| HK1049790A1 (zh) | 2003-05-30 |
| BR0013277A (pt) | 2002-06-18 |
| NO20020687L (no) | 2002-04-03 |
| EA200200249A1 (ru) | 2002-08-29 |
| DE60034683D1 (de) | 2007-06-14 |
| PL354058A1 (en) | 2003-12-15 |
| EP1202734A1 (en) | 2002-05-08 |
| ZA200201118B (en) | 2003-05-28 |
| PE20010482A1 (es) | 2001-04-20 |
| CA2380786A1 (en) | 2001-02-22 |
| NZ517238A (en) | 2004-01-30 |
| MXPA02001497A (es) | 2003-07-21 |
| WO2001012188A1 (en) | 2001-02-22 |
| NO20020687D0 (no) | 2002-02-11 |
| US6387900B1 (en) | 2002-05-14 |
| KR20020060158A (ko) | 2002-07-16 |
| SK2082002A3 (en) | 2002-09-10 |
| CO5200848A1 (es) | 2002-09-27 |
| DE60034683T2 (de) | 2008-01-17 |
| AU6747000A (en) | 2001-03-13 |
| IL147925A0 (en) | 2002-08-14 |
| AR035557A1 (es) | 2004-06-16 |
| HUP0301857A2 (hu) | 2003-09-29 |
| EP1202734B1 (en) | 2007-05-02 |
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