JP2007529422A - 抗ウイルス治療 - Google Patents
抗ウイルス治療 Download PDFInfo
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- JP2007529422A JP2007529422A JP2006551523A JP2006551523A JP2007529422A JP 2007529422 A JP2007529422 A JP 2007529422A JP 2006551523 A JP2006551523 A JP 2006551523A JP 2006551523 A JP2006551523 A JP 2006551523A JP 2007529422 A JP2007529422 A JP 2007529422A
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- JP
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- Prior art keywords
- alkyl
- cycloalkenyl
- aryl
- heteroaryl
- aminocarbonyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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- 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
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- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A—HUMAN NECESSITIES
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Landscapes
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US54044404P | 2004-01-29 | 2004-01-29 | |
| PCT/US2005/002897 WO2005072412A2 (en) | 2004-01-29 | 2005-01-31 | Anti-viral therapeutics |
Publications (2)
| Publication Number | Publication Date |
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| JP2007529422A true JP2007529422A (ja) | 2007-10-25 |
| JP2007529422A5 JP2007529422A5 (https=) | 2008-03-13 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP2006551523A Withdrawn JP2007529422A (ja) | 2004-01-29 | 2005-01-31 | 抗ウイルス治療 |
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| Country | Link |
|---|---|
| US (1) | US20060019952A1 (https=) |
| EP (1) | EP1715855A4 (https=) |
| JP (1) | JP2007529422A (https=) |
| AU (1) | AU2005208938A1 (https=) |
| CA (1) | CA2553670A1 (https=) |
| WO (1) | WO2005072412A2 (https=) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012513481A (ja) * | 2008-12-23 | 2012-06-14 | プレジデント アンド フェロウズ オブ ハーバード カレッジ | ネクロトーシスの小分子阻害剤 |
| US9725452B2 (en) | 2013-03-15 | 2017-08-08 | Presidents And Fellows Of Harvard College | Substituted indoles and pyrroles as RIP kinase inhibitors |
| JP2018529714A (ja) * | 2015-09-30 | 2018-10-11 | ギリアード サイエンシーズ， インコーポレイテッド | Ｈｉｖの処置のための化合物および組合せ物 |
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| EP4352059A1 (en) | 2021-06-09 | 2024-04-17 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| WO2022261159A1 (en) | 2021-06-09 | 2022-12-15 | Incyte Corporation | Tricyclic heterocycles as fgfr inhibitors |
| CN119173514A (zh) | 2022-03-17 | 2024-12-20 | 因赛特公司 | 作为jak2 v617f抑制剂的三环脲化合物 |
| CN116919949B (zh) * | 2023-08-31 | 2024-03-22 | 中国医学科学院医药生物技术研究所 | 2-氨基-5-苯基噻吩-3-羧酸酰胺在制备抗新型冠状病毒药物中的应用 |
Family Cites Families (8)
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| US5308612A (en) * | 1992-08-12 | 1994-05-03 | Blue Marble Research, Inc. | Uses of polystyrenesulfonate and related compounds as inhibitors of transactivating transcription factor (TAT) and as therapeutics for HIV infection and AIDS |
| US6335358B1 (en) * | 1995-04-12 | 2002-01-01 | President And Fellows Of Harvard College | Lactacystin analogs |
| CA2281925A1 (en) * | 1997-02-26 | 1998-09-03 | Ciblex Corporation | Inhibitors of leaderless protein export |
| US6262055B1 (en) * | 1998-06-03 | 2001-07-17 | Merck & Co., Inc. | HIV integrase inhibitors |
| JP3929244B2 (ja) * | 1998-12-25 | 2007-06-13 | 塩野義製薬株式会社 | Ｈｉｖインテグラーゼ阻害活性を有する芳香族ヘテロ環誘導体 |
| US20040005574A1 (en) * | 2002-07-08 | 2004-01-08 | Leonard Guarente | SIR2 activity |
| EP1429765A2 (en) * | 2001-09-14 | 2004-06-23 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| US7351542B2 (en) * | 2002-05-20 | 2008-04-01 | The Regents Of The University Of California | Methods of modulating tubulin deacetylase activity |
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- 2005-01-31 AU AU2005208938A patent/AU2005208938A1/en not_active Abandoned
- 2005-01-31 CA CA002553670A patent/CA2553670A1/en not_active Abandoned
- 2005-01-31 US US11/048,490 patent/US20060019952A1/en not_active Abandoned
- 2005-01-31 WO PCT/US2005/002897 patent/WO2005072412A2/en not_active Ceased
- 2005-01-31 EP EP05712361A patent/EP1715855A4/en not_active Withdrawn
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012513481A (ja) * | 2008-12-23 | 2012-06-14 | プレジデント アンド フェロウズ オブ ハーバード カレッジ | ネクロトーシスの小分子阻害剤 |
| US9586880B2 (en) | 2008-12-23 | 2017-03-07 | President And Fellows Of Harvard College | Small molecule inhibitors of necroptosis |
| US9725452B2 (en) | 2013-03-15 | 2017-08-08 | Presidents And Fellows Of Harvard College | Substituted indoles and pyrroles as RIP kinase inhibitors |
| JP2018529714A (ja) * | 2015-09-30 | 2018-10-11 | ギリアード サイエンシーズ， インコーポレイテッド | Ｈｉｖの処置のための化合物および組合せ物 |
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| US20060019952A1 (en) | 2006-01-26 |
| CA2553670A1 (en) | 2005-08-11 |
| WO2005072412A3 (en) | 2007-03-22 |
| AU2005208938A1 (en) | 2005-08-11 |
| EP1715855A2 (en) | 2006-11-02 |
| EP1715855A4 (en) | 2010-06-16 |
| WO2005072412A2 (en) | 2005-08-11 |
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