BRPI0620865A2 - métodos para melhorar a farmacocinética de inibidores das integrases do hiv - Google Patents
métodos para melhorar a farmacocinética de inibidores das integrases do hiv Download PDFInfo
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- BRPI0620865A2 BRPI0620865A2 BRPI0620865-7A BRPI0620865A BRPI0620865A2 BR PI0620865 A2 BRPI0620865 A2 BR PI0620865A2 BR PI0620865 A BRPI0620865 A BR PI0620865A BR PI0620865 A2 BRPI0620865 A2 BR PI0620865A2
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- compound
- pharmaceutically acceptable
- acceptable salt
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Landscapes
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| PCT/US2006/049668 WO2007079260A1 (en) | 2005-12-30 | 2006-12-29 | Methods for improving the pharmacokinetics of hiv integrase inhibitors |
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| EP (2) | EP2308490A1 (https=) |
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| BR (1) | BRPI0620865A2 (https=) |
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| EA (2) | EA201201496A1 (https=) |
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| US20090233964A1 (en) * | 2005-12-30 | 2009-09-17 | Gilead Sciences, Inc. | Methods for improving the pharmacokinetics of hiv integrase inhibitors |
| PL3150586T3 (pl) | 2007-02-23 | 2020-06-01 | Gilead Sciences, Inc. | Modulatory farmakokinetycznych właściwości środków terapeutycznych |
| WO2009006199A1 (en) * | 2007-06-29 | 2009-01-08 | Gilead Sciences, Inc. | Therapeutic compositions and the use thereof |
| AR067184A1 (es) * | 2007-06-29 | 2009-09-30 | Gilead Sciences Inc | Uso de 6-(3-cloro-2-fluorbencil)-1-[(2s)-1-hidroxi-3-metilbutan-2-il]-7-metoxi-4-oxo-1,4-dihidroquinolina-3-carboxilico. composicion farmaceutica |
| US20110117193A1 (en) * | 2008-01-17 | 2011-05-19 | Duquesne University Of The Holy Spirit | Antiretroviral drug formulations for treatment of children exposed to hiv/aids |
| PE20121524A1 (es) | 2010-01-27 | 2012-12-03 | Viiv Healthcare Co | Combinaciones de compuestos que comprenden inhibidores de la integrasa de vih y otros agentes terapeuticos |
| WO2013109354A2 (en) * | 2011-12-07 | 2013-07-25 | Texas Southern University | Etravirine formulations and uses thereof |
| EA030003B1 (ru) | 2012-12-21 | 2018-06-29 | Джилид Сайэнс, Инк. | Полициклическое карбамоилпиридоновое соединение и его фармацевтическое применение для лечения вич-инфекции |
| SI3019503T1 (sl) | 2013-07-12 | 2017-11-30 | Gilead Sciences, Inc. | Policiklične karbamoilpiridonske spojine in njihova uporaba za zdravljenje HIV infekcij |
| NO2865735T3 (https=) | 2013-07-12 | 2018-07-21 | ||
| TWI677489B (zh) | 2014-06-20 | 2019-11-21 | 美商基利科學股份有限公司 | 多環型胺甲醯基吡啶酮化合物之合成 |
| NO2717902T3 (https=) | 2014-06-20 | 2018-06-23 | ||
| TW201613936A (en) | 2014-06-20 | 2016-04-16 | Gilead Sciences Inc | Crystalline forms of(2R,5S,13aR)-8-hydroxy-7,9-dioxo-n-(2,4,6-trifluorobenzyl)-2,3,4,5,7,9,13,13a-octahydro-2,5-methanopyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide |
| TWI695003B (zh) | 2014-12-23 | 2020-06-01 | 美商基利科學股份有限公司 | 多環胺甲醯基吡啶酮化合物及其醫藥用途 |
| DK3236972T3 (en) | 2014-12-26 | 2021-10-04 | Univ Emory | Antivirale N4-hydroxycytidin-derivativer |
| JP6402259B2 (ja) | 2015-04-02 | 2018-10-10 | ギリアード サイエンシーズ， インコーポレイテッド | 多環式カルバモイルピリドン化合物およびそれらの薬学的使用 |
| SG11201802983TA (en) | 2015-11-09 | 2018-05-30 | Gilead Sciences Inc | Therapeutic compositions for treatment of human immunodeficiency virus |
| JP6804790B1 (ja) | 2017-12-07 | 2020-12-23 | エモリー ユニバーシティー | Ｎ４−ヒドロキシシチジンおよび誘導体ならびにそれらに関連する抗ウイルス用途 |
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| US5354866A (en) * | 1989-05-23 | 1994-10-11 | Abbott Laboratories | Retroviral protease inhibiting compounds |
| US5552558A (en) * | 1989-05-23 | 1996-09-03 | Abbott Laboratories | Retroviral protease inhibiting compounds |
| EP1302468B1 (en) | 1992-12-29 | 2008-12-17 | Abbott Laboratories | Processes and intermediates for manufacturing retroviral protease inhibiting compounds |
| US5567823A (en) | 1995-06-06 | 1996-10-22 | Abbott Laboratories | Process for the preparation of an HIV protease inhibiting compound |
| US6037157A (en) | 1995-06-29 | 2000-03-14 | Abbott Laboratories | Method for improving pharmacokinetics |
| ATE332132T1 (de) * | 1999-06-04 | 2006-07-15 | Abbott Lab | Verbesserte arzneizubereitungen enthaltend ritonavir |
| US6541515B2 (en) * | 2000-08-09 | 2003-04-01 | Merck & Co., Inc. | HIV integrase inhibitors |
| US6407128B1 (en) * | 2001-12-03 | 2002-06-18 | Elan Pharmaceuticals, Inc. | Method for increasing the bioavailability of metaxalone |
| TWI286476B (en) * | 2001-12-12 | 2007-09-11 | Tibotec Pharm Ltd | Combination of cytochrome P450 dependent protease inhibitors |
| US20040157804A1 (en) | 2002-10-16 | 2004-08-12 | Gilead Sciences, Inc. | Pre-organized tricyclic integrase inhibitor compounds |
| EP2161258A3 (en) | 2002-11-20 | 2010-04-07 | Japan Tabacco Inc. | 4-oxoquinoline compound and use thereof as hiv integrase inhibitor |
| JP3567162B1 (ja) * | 2002-11-20 | 2004-09-22 | 日本たばこ産業株式会社 | ４−オキソキノリン化合物及びそのｈｉｖインテグラーゼ阻害剤としての利用 |
| BRPI0407052A (pt) * | 2003-01-27 | 2006-01-17 | Pfizer | Inibidores da hiv-integrase, composições farmacêuticas, e métodos para sua utilização |
| US7812016B2 (en) * | 2003-05-13 | 2010-10-12 | Smithkline Beecham Corporation | Naphthyridine integrase inhibitors |
| MY134672A (en) | 2004-05-20 | 2007-12-31 | Japan Tobacco Inc | Stable crystal of 4-oxoquinoline compound |
| WO2005113509A1 (en) * | 2004-05-20 | 2005-12-01 | Japan Tobacco Inc. | Novel 4-oxoquinoline compound and use thereof as hiv integrase inhibitor |
| EP3287130A1 (en) * | 2004-05-21 | 2018-02-28 | Japan Tobacco Inc. | Combinations comprising a 4-isoquinolone derivative and protease inhibitors |
| NZ563361A (en) * | 2005-06-02 | 2011-02-25 | Schering Corp | HCV protease inhibitors in combination with food |
| US20090233964A1 (en) * | 2005-12-30 | 2009-09-17 | Gilead Sciences, Inc. | Methods for improving the pharmacokinetics of hiv integrase inhibitors |
| EA022099B1 (ru) * | 2006-09-12 | 2015-11-30 | Джилид Сайэнс, Инк. | Способы и интермедиаты для получения ингибиторов интегразы |
| WO2009006199A1 (en) * | 2007-06-29 | 2009-01-08 | Gilead Sciences, Inc. | Therapeutic compositions and the use thereof |
| AR067184A1 (es) * | 2007-06-29 | 2009-09-30 | Gilead Sciences Inc | Uso de 6-(3-cloro-2-fluorbencil)-1-[(2s)-1-hidroxi-3-metilbutan-2-il]-7-metoxi-4-oxo-1,4-dihidroquinolina-3-carboxilico. composicion farmaceutica |
| AR068403A1 (es) * | 2007-09-11 | 2009-11-18 | Gilead Sciences Inc | Proceso e intermediarios para la preparacion de inhibidores de integrasa |
-
2006
- 2006-12-29 JP JP2008548784A patent/JP4676536B2/ja active Active
- 2006-12-29 KR KR1020087018651A patent/KR101524165B1/ko active Active
- 2006-12-29 HR HR20080313A patent/HRP20080313A2/xx not_active Application Discontinuation
- 2006-12-29 KR KR1020167016288A patent/KR20160074018A/ko not_active Ceased
- 2006-12-29 US US11/647,858 patent/US20070219243A1/en not_active Abandoned
- 2006-12-29 SG SG201102227-4A patent/SG170795A1/en unknown
- 2006-12-29 WO PCT/US2006/049668 patent/WO2007079260A1/en not_active Ceased
- 2006-12-29 EA EA201201496A patent/EA201201496A1/ru unknown
- 2006-12-29 BR BRPI0620865-7A patent/BRPI0620865A2/pt not_active IP Right Cessation
- 2006-12-29 SG SG201102229-0A patent/SG170796A1/en unknown
- 2006-12-29 NZ NZ569576A patent/NZ569576A/en unknown
- 2006-12-29 CN CN201410249622.8A patent/CN104069108A/zh active Pending
- 2006-12-29 AU AU2006332664A patent/AU2006332664B2/en active Active
- 2006-12-29 EP EP20100193364 patent/EP2308490A1/en not_active Withdrawn
- 2006-12-29 CA CA2847871A patent/CA2847871C/en active Active
- 2006-12-29 KR KR1020147014797A patent/KR20140082858A/ko not_active Ceased
- 2006-12-29 EP EP06848393A patent/EP1976517A1/en not_active Withdrawn
- 2006-12-29 EA EA200801619A patent/EA018544B1/ru unknown
- 2006-12-29 AP AP2008004522A patent/AP2702A/xx active
- 2006-12-29 CA CA2635468A patent/CA2635468C/en active Active
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2008
- 2008-06-16 IL IL192208A patent/IL192208A/en active IP Right Grant
- 2008-07-29 NO NO20083333A patent/NO20083333L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| WO2007079260A9 (en) | 2007-08-30 |
| EP2308490A1 (en) | 2011-04-13 |
| JP4676536B2 (ja) | 2011-04-27 |
| IL192208A0 (en) | 2009-02-11 |
| US20070219243A1 (en) | 2007-09-20 |
| AU2006332664A1 (en) | 2007-07-12 |
| KR101524165B1 (ko) | 2015-06-01 |
| CA2847871A1 (en) | 2007-07-12 |
| EP1976517A1 (en) | 2008-10-08 |
| CA2635468C (en) | 2016-08-09 |
| AP2008004522A0 (en) | 2008-06-30 |
| EA201201496A1 (ru) | 2013-07-30 |
| CN104069108A (zh) | 2014-10-01 |
| JP2009525265A (ja) | 2009-07-09 |
| CA2635468A1 (en) | 2007-07-12 |
| KR20160074018A (ko) | 2016-06-27 |
| CA2847871C (en) | 2016-07-26 |
| EA200801619A1 (ru) | 2008-10-30 |
| IL192208A (en) | 2013-10-31 |
| SG170796A1 (en) | 2011-05-30 |
| EA018544B1 (ru) | 2013-08-30 |
| KR20140082858A (ko) | 2014-07-02 |
| NZ569576A (en) | 2011-09-30 |
| SG170795A1 (en) | 2011-05-30 |
| HRP20080313A2 (en) | 2008-11-30 |
| WO2007079260A1 (en) | 2007-07-12 |
| AU2006332664B2 (en) | 2013-03-14 |
| AP2702A (en) | 2013-07-23 |
| KR20080081358A (ko) | 2008-09-09 |
| NO20083333L (no) | 2008-09-29 |
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