JP2011503103A - タンパク質輸送の調節方法 - Google Patents
タンパク質輸送の調節方法 Download PDFInfo
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- 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
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Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| AU2003225933A1 (en) * | 2002-03-22 | 2003-10-13 | Cellular Genomics, Inc. | AN IMPROVED FORMULATION OF CERTAIN PYRAZOLO(3,4-d) PYRIMIDINES AS KINASE MODULATORS |
| UA80171C2 (en) * | 2002-12-19 | 2007-08-27 | Pfizer Prod Inc | Pyrrolopyrimidine derivatives |
| EP1631268A2 (en) * | 2003-05-21 | 2006-03-08 | Board Of Regents The University Of Texas System | Inhibition of protein kinase c-mu (pkd) as a treatment for cardiac hypertrophy and heart failure |
| US7429596B2 (en) * | 2003-06-20 | 2008-09-30 | The Regents Of The University Of California | 1H-pyrrolo [2,3-D] pyrimidine derivatives and methods of use thereof |
| WO2005112936A1 (en) * | 2004-05-14 | 2005-12-01 | The Regents Of The University Of Michigan | Compositions and methods relating to protein kinase inhibitors |
| US20060094682A1 (en) * | 2004-10-29 | 2006-05-04 | Odyssey Thera, Inc. | Kinase inhibitors for the treatment of diabetes and obesity |
| US9512125B2 (en) * | 2004-11-19 | 2016-12-06 | The Regents Of The University Of California | Substituted pyrazolo[3.4-D] pyrimidines as anti-inflammatory agents |
| US20090270431A1 (en) * | 2005-10-19 | 2009-10-29 | The University Of Georgia Research Foundation | Cyclopentenol Nucleoside Compounds Intermediates for their Synthesis and Methods of Treating Viral Infections |
| JP2009531443A (ja) * | 2006-03-29 | 2009-09-03 | フォールドアールエックス ファーマシューティカルズ インコーポレーティッド | α−シヌクレイン毒性の抑制 |
| WO2008147687A1 (en) * | 2007-05-21 | 2008-12-04 | Mayo Foundation For Medical Education And Research | Treating pancreatitis |
-
2008
- 2008-11-07 AU AU2008323694A patent/AU2008323694A1/en not_active Abandoned
- 2008-11-07 CN CN200880124202XA patent/CN101917999A/zh active Pending
- 2008-11-07 WO PCT/US2008/082909 patent/WO2009062118A2/en not_active Ceased
- 2008-11-07 US US12/741,992 patent/US20100331297A1/en not_active Abandoned
- 2008-11-07 BR BRPI0820342-3A patent/BRPI0820342A2/pt not_active IP Right Cessation
- 2008-11-07 CA CA2705303A patent/CA2705303A1/en not_active Abandoned
- 2008-11-07 JP JP2010533304A patent/JP2011503103A/ja not_active Withdrawn
- 2008-11-07 EA EA201070572A patent/EA201070572A1/ru unknown
- 2008-11-07 EP EP08848219A patent/EP2217239A2/en not_active Withdrawn
-
2010
- 2010-05-25 ZA ZA2010/03725A patent/ZA201003725B/en unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| CN101917999A (zh) | 2010-12-15 |
| CA2705303A1 (en) | 2009-05-14 |
| ZA201003725B (en) | 2011-03-30 |
| WO2009062118A3 (en) | 2009-12-30 |
| EP2217239A2 (en) | 2010-08-18 |
| AU2008323694A1 (en) | 2009-05-14 |
| WO2009062118A2 (en) | 2009-05-14 |
| US20100331297A1 (en) | 2010-12-30 |
| BRPI0820342A2 (pt) | 2015-05-26 |
| EA201070572A1 (ru) | 2010-12-30 |
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