EA023715B1 - Вещество, применяемое для лечения заболеваний, опосредованных pi3-киназой - Google Patents
Вещество, применяемое для лечения заболеваний, опосредованных pi3-киназой Download PDFInfo
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- EA023715B1 EA023715B1 EA201491675A EA201491675A EA023715B1 EA 023715 B1 EA023715 B1 EA 023715B1 EA 201491675 A EA201491675 A EA 201491675A EA 201491675 A EA201491675 A EA 201491675A EA 023715 B1 EA023715 B1 EA 023715B1
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- Eurasian Patent Office
- Prior art keywords
- compound
- formula
- lactose
- solid crystalline
- anhydrous form
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| PCT/GB2013/050624 WO2013136076A1 (en) | 2012-03-13 | 2013-03-13 | Crystalline pi3 kinase inhibitors |
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| EA201491674A EA025465B1 (ru) | 2012-03-13 | 2013-03-13 | СПОСОБ ПОВЫШЕНИЯ СТАБИЛЬНОСТИ К ХИМИЧЕСКОМУ РАЗЛОЖЕНИЮ ФАРМАЦЕВТИЧЕСКОЙ КОМПОЗИЦИИ, СОДЕРЖАЩЕЙ 6-(2-((4-АМИНО-3-(3-ГИДРОКСИФЕНИЛ)-1Н-ПИРАЗОЛО[3,4-d]ПИРИМИДИН-1-ИЛ)МЕТИЛ)-3-(2-ХЛОРБЕНЗИЛ)-4-ОКСО-3,4-ДИГИДРОХИНАЗОЛИН-5-ИЛ)-N,N-БИС(2-МЕТОКСИЭТИЛ)ГЕКС-5-ИНАМИД |
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| SG11201404522VA (en) | 2012-03-13 | 2014-10-30 | Respivert Ltd | Crystalline pi3 kinase inhibitors |
| US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
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| AR095353A1 (es) | 2013-03-15 | 2015-10-07 | Respivert Ltd | Compuesto |
| TW201522341A (zh) | 2013-03-15 | 2015-06-16 | Respivert Ltd | 化合物 |
| SG10201902074UA (en) | 2013-10-04 | 2019-04-29 | Infinity Pharmaceuticals Inc | Heterocyclic compounds and uses thereof |
| WO2015051241A1 (en) | 2013-10-04 | 2015-04-09 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| PT3119397T (pt) | 2014-03-19 | 2022-04-11 | Infinity Pharmaceuticals Inc | Compostos heterocíclicos para utilização no tratamento de distúrbios mediados por pi3k-gama |
| EP3164400A1 (en) | 2014-07-04 | 2017-05-10 | Lupin Limited | Quinolizinone derivatives as pi3k inhibitors |
| ES2701525T3 (es) * | 2014-07-09 | 2019-02-22 | Arven Ilac Sanayi Ve Ticaret As | Un procedimiento para la preparación de formulaciones para inhalación |
| WO2016054491A1 (en) | 2014-10-03 | 2016-04-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| KR102787845B1 (ko) | 2015-09-14 | 2025-03-31 | 트웰브 테라퓨틱스, 아이엔씨. | 이소퀴놀리논의 고체형, 그의 제조 방법, 이를 포함하는 조성물 및 이를 사용하는 방법 |
| US10759806B2 (en) | 2016-03-17 | 2020-09-01 | Infinity Pharmaceuticals, Inc. | Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as PI3K kinase inhibitors |
| JP7166929B2 (ja) * | 2016-04-15 | 2022-11-08 | チア タイ ティエンチン ファーマシューティカル グループ カンパニー リミテッド | イソグリチルリチン酸またはその塩の吸入製剤および呼吸器疾患を治療する薬物の製造におけるそれらの使用 |
| US10919914B2 (en) | 2016-06-08 | 2021-02-16 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
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Family Cites Families (58)
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| GB9501841D0 (en) | 1995-01-31 | 1995-03-22 | Co Ordinated Drug Dev | Improvements in and relating to carrier particles for use in dry powder inhalers |
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| US6667300B2 (en) | 2000-04-25 | 2003-12-23 | Icos Corporation | Inhibitors of human phosphatidylinositol 3-kinase delta |
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| US6608053B2 (en) | 2000-04-27 | 2003-08-19 | Yamanouchi Pharmaceutical Co., Ltd. | Fused heteroaryl derivatives |
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| AU2002317377A1 (en) | 2001-07-20 | 2003-03-03 | Cancer Research Technology Limited | Biphenyl apurinic/apyrimidinic site endonuclease inhibitors to treat cancer |
| WO2004037176A2 (en) | 2002-10-21 | 2004-05-06 | Bristol-Myers Squibb Company | Quinazolinones and derivatives thereof as factor xa inhibitors |
| JP4736043B2 (ja) | 2003-03-14 | 2011-07-27 | 小野薬品工業株式会社 | 含窒素複素環誘導体およびそれらを有効成分とする薬剤 |
| US7122557B2 (en) | 2003-03-18 | 2006-10-17 | Bristol-Myers Squibb Company | Sulfonyl-amidino-containing and tetrahydropyrimidino-containing compounds as factor Xa inhibitors |
| CA2520121A1 (en) | 2003-04-03 | 2004-10-21 | Protein Design Labs, Inc. | Inhibitors of integrin alpha5beta1 and their use for the control of tissue granulation |
| 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 |
| GB0316341D0 (en) * | 2003-07-11 | 2003-08-13 | Glaxo Group Ltd | Pharmaceutical formulations |
| EP1643973A1 (en) * | 2003-07-11 | 2006-04-12 | Glaxo Group Limited | Pharmaceutical formulations comprising magnesium stearate |
| JPWO2005012221A1 (ja) | 2003-08-04 | 2006-09-14 | 小野薬品工業株式会社 | ジフェニルエーテル化合物、その製造方法および用途 |
| WO2005016349A1 (en) | 2003-08-14 | 2005-02-24 | Icos Corporation | Methods of inhibiting leukocyte accumulation |
| WO2005016348A1 (en) | 2003-08-14 | 2005-02-24 | Icos Corporation | Method of inhibiting immune responses stimulated by an endogenous factor |
| GB0326632D0 (en) | 2003-11-14 | 2003-12-17 | Jagotec Ag | Dry powder formulations |
| US20050239809A1 (en) | 2004-01-08 | 2005-10-27 | Watts Stephanie W | Methods for treating and preventing hypertension and hypertension-related disorders |
| CN102229609A (zh) * | 2004-05-13 | 2011-11-02 | 艾科斯有限公司 | 作为人磷脂酰肌醇3-激酶δ抑制剂的喹唑啉酮 |
| CA2566436C (en) | 2004-05-13 | 2011-05-10 | Vanderbilt University | Phosphoinositide 3-kinase delta selective inhibitors for inhibiting angiogenesis |
| EP1755609A1 (en) | 2004-05-25 | 2007-02-28 | Icos Corporation | Methods for treating and/or preventing aberrant proliferation of hematopoietic cells |
| EP1750715A1 (en) | 2004-06-04 | 2007-02-14 | Icos Corporation | Methods for treating mast cell disorders |
| TWI400232B (zh) | 2004-09-13 | 2013-07-01 | Ono Pharmaceutical Co | 含氮雜環衍生物及以該含氮雜環衍生物為有效成分之藥劑 |
| GB0425758D0 (en) | 2004-11-23 | 2004-12-22 | Vectura Ltd | Preparation of pharmaceutical compositions |
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| GB0525254D0 (en) | 2005-12-12 | 2006-01-18 | Jagotec Ag | Powder compositions for inhalation |
| US20080032960A1 (en) | 2006-04-04 | 2008-02-07 | Regents Of The University Of California | PI3 kinase antagonists |
| CN101448505A (zh) * | 2006-04-04 | 2009-06-03 | 加利福尼亚大学董事会 | Pi3激酶拮抗剂 |
| WO2007134876A2 (en) | 2006-05-24 | 2007-11-29 | Bayer Schering Pharma Aktiengesellschaft | HIGH AFFINITY HUMAN AND HUMANIZED ANTI-α5β1 INTEGRIN FUNCTION BLOCKING ANTIBODIES WITH REDUCED IMMUNOGENICITY |
| CN101506198A (zh) | 2006-06-29 | 2009-08-12 | 先灵公司 | 取代的双环和三环凝血酶受体拮抗剂 |
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| WO2008067219A2 (en) | 2006-11-29 | 2008-06-05 | Kalypsys, Inc. | Quinazolinone modulators of tgr5 |
| WO2008104077A1 (en) | 2007-02-28 | 2008-09-04 | Methylgene Inc. | Small molecule inhibitors of protein arginine methyltransferases (prmts) |
| AR066477A1 (es) | 2007-05-09 | 2009-08-19 | Novartis Ag | Imidazopiridazinas sustituidas como inhibidores de cinasa de lipido |
| WO2008140750A1 (en) | 2007-05-10 | 2008-11-20 | Hydra Biosciences Inc. | Compounds for modulating trpv3 function |
| MX2010007418A (es) | 2008-01-04 | 2010-11-12 | Intellikine Inc | Ciertas entidades quimicas, composiciones y metodos. |
| JP5731978B2 (ja) | 2008-09-26 | 2015-06-10 | インテリカイン， エルエルシー | 複素環キナーゼ阻害剤 |
| WO2010059593A1 (en) | 2008-11-18 | 2010-05-27 | Intellikine, Inc. | Methods and compositions for treatment of ophthalmic conditions |
| US20110294803A1 (en) | 2008-12-04 | 2011-12-01 | Law Amanda J | Phosphatidylinositol-3-kinase p110 delta-targeted drugs in the treatment of cns disorders |
| US8658648B2 (en) | 2008-12-05 | 2014-02-25 | Designmedix, Inc. | Modified chloroquines with single ring moiety or fused ring moiety |
| US20110135655A1 (en) | 2009-01-13 | 2011-06-09 | PHILADELPHIA HEALTH AND EDUCATION CORPORATION d/b/a Drexel University College of Medicine; | Role of PI3K p110 delta Signaling in Retroviral Infection and Replication |
| PE20120602A1 (es) | 2009-03-24 | 2012-05-21 | Gilead Calistoga Llc | ATROPISOMEROS DE 2-[(6-AMINO-9H-PURIN-9-IL)METIL]-5-METIL-3-o-TOLILQUINAZOLIN-4(3H)-ONA |
| JP2013501008A (ja) | 2009-08-05 | 2013-01-10 | バーシテック リミテッド | 抗ウイルス性化合物ならびにそれを含む医薬組成物 |
| WO2011083387A1 (en) | 2010-01-07 | 2011-07-14 | Pfizer Limited | Hydrochloride salt of biphenyl-2-yl-carbamic acid 1-{9-[(3-fluoro-4-hydroxy-benzoyl)-methyl-amino]-nonyl}-piperidin-4-yl ester |
| CN201676365U (zh) * | 2010-03-29 | 2010-12-22 | 山东京卫制药有限公司 | 带有语音提示的给药吸入装置 |
| CN201692450U (zh) * | 2010-06-22 | 2011-01-05 | 于清 | 用于药物输送的高效干粉吸入器 |
| EP2954888A1 (en) * | 2010-08-31 | 2015-12-16 | GlaxoSmithKline Intellectual Property Development Limited | Dry powder inhalation drug products exhibiting moisture control properties and methods of administering the same |
| KR101886987B1 (ko) | 2010-09-30 | 2018-08-08 | 키에시 파르마슈티시 엣스. 피. 에이. | 흡입용 건조 분말 제제 내 마그네슘 스테아레이트의 용도 |
| CN202154919U (zh) * | 2011-05-03 | 2012-03-07 | 王晓明 | 一种防交叉感染雾化吸入装置 |
| SG11201404522VA (en) | 2012-03-13 | 2014-10-30 | Respivert Ltd | Crystalline pi3 kinase inhibitors |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011048111A1 (en) * | 2009-10-19 | 2011-04-28 | Respivert Limited | Compounds |
| WO2012052753A1 (en) * | 2010-10-18 | 2012-04-26 | Respivert Limited | Quinazolin-4 (3h) -one derivatives used as pi3 kinase inhibitors |
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