JP2011503193A - ヒトホスファチジルイノシトール３−キナーゼδの阻害剤 - Google Patents
ヒトホスファチジルイノシトール３−キナーゼδの阻害剤 Download PDFInfo
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011508782A (ja) * | 2008-01-04 | 2011-03-17 | インテリカイン， インコーポレイテッド | 特定の化学的実体、組成物および方法 |
| JP2014520888A (ja) * | 2011-07-19 | 2014-08-25 | インフィニティー ファーマシューティカルズ， インコーポレイテッド | 複素環式化合物及びその使用 |
| JP2014520887A (ja) * | 2011-07-19 | 2014-08-25 | インフィニティー ファーマシューティカルズ， インコーポレイテッド | 複素環式化合物及びその使用 |
| JP2015509509A (ja) * | 2012-03-06 | 2015-03-30 | ベイジン ウェイフオン イーミーン バイオ−テクノロジー リミティドカンパニー | 慢性閉塞性疾患を治療するための医薬品組成物の製造のための、ルパタジンの使用 |
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| US7754208B2 (en) | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, Inc. | Binding domain-immunoglobulin fusion proteins |
| US20030133939A1 (en) | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
| DE10238722A1 (de) | 2002-08-23 | 2004-03-11 | Bayer Ag | Selektive Phosphodiesterase 9A-Inhibitoren als Arzneimittel zur Verbesserung kognitiver Prozesse |
| DE10320785A1 (de) | 2003-05-09 | 2004-11-25 | Bayer Healthcare Ag | 6-Arylmethyl-substituierte Pyrazolopyrimidine |
| US8044060B2 (en) | 2003-05-09 | 2011-10-25 | Boehringer Ingelheim International Gmbh | 6-cyclylmethyl- and 6-alkylmethyl pyrazolo[3,4-D]pyrimidines, methods for their preparation and methods for their use to treat impairments of perception, concentration learning and/or memory |
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| SG10201403526YA (en) | 2005-07-25 | 2014-10-30 | Emergent Product Dev Seattle | B-cell reduction using cd37-specific and cd20-specific binding molecules |
| KR20090017498A (ko) | 2006-04-04 | 2009-02-18 | 더 리젠트스 오브 더 유니이버시티 오브 캘리포니아 | Ｐｉ３ 키나제 길항물질 |
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| UA105362C2 (en) | 2008-04-02 | 2014-05-12 | Бьорингер Ингельхайм Интернациональ Гмбх | 1-heterocyclyl-1, 5-dihydro-pyrazolo [3, 4-d] pyrimidin-4-one derivatives and their use as pde9a modulators |
| ES2368700T3 (es) | 2008-04-11 | 2011-11-21 | Emergent Product Development Seattle, Llc | Agente inmunoterapéutico para cd37 y combinación con un agente quimioterapéutico bifuncional del mismo. |
| US20110224223A1 (en) | 2008-07-08 | 2011-09-15 | The Regents Of The University Of California, A California Corporation | MTOR Modulators and Uses Thereof |
| BRPI0915231A2 (pt) | 2008-07-08 | 2018-06-12 | Intellikine Inc | compostos inibidores de quinase e métodos de uso |
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| DK2358720T3 (en) | 2008-10-16 | 2016-06-06 | Univ California | Heteroarylkinaseinhibitorer fused-ring |
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| US9724354B2 (en) | 2013-03-22 | 2017-08-08 | Millennium Pharmaceuticals, Inc. | Combination of catalytic mTORC1/2 inhibitors and selective inhibitors of Aurora A kinase |
| NZ631142A (en) | 2013-09-18 | 2016-03-31 | Axikin Pharmaceuticals Inc | Pharmaceutically acceptable salts of 3,5-diaminopyrazole kinase inhibitors |
| RU2675105C9 (ru) | 2013-09-22 | 2019-01-09 | Саншайн Лейк Фарма Ко., Лтд. | Замещенные аминопиримидиновые соединения и способы их использования |
| WO2015051241A1 (en) | 2013-10-04 | 2015-04-09 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| SG10201902074UA (en) | 2013-10-04 | 2019-04-29 | Infinity Pharmaceuticals Inc | Heterocyclic compounds and uses thereof |
| CN113616656B (zh) | 2014-03-19 | 2023-02-17 | 无限药品股份有限公司 | 用于治疗PI3K-γ介导的障碍的杂环化合物 |
| WO2015160975A2 (en) | 2014-04-16 | 2015-10-22 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| MX2017000208A (es) | 2014-07-04 | 2017-05-01 | Lupin Ltd | Derivados de quinolizinona como inhibidores de pi3k. |
| WO2016054491A1 (en) | 2014-10-03 | 2016-04-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| MY191736A (en) | 2014-12-23 | 2022-07-13 | Axikin Pharmaceuticals Inc | 3,5-diaminopyrazole kinase inhibitors |
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| AU2016322552B2 (en) | 2015-09-14 | 2021-03-25 | Infinity Pharmaceuticals, Inc. | Solid forms of isoquinolinone derivatives, process of making, compositions comprising, and methods of using the same |
| WO2017053469A2 (en) | 2015-09-21 | 2017-03-30 | Aptevo Research And Development Llc | Cd3 binding polypeptides |
| CN107033145B (zh) * | 2016-02-04 | 2019-11-22 | 浙江大学 | 苯并噻嗪和苯并噻二嗪类化合物及制备和应用 |
| WO2017161116A1 (en) | 2016-03-17 | 2017-09-21 | Infinity Pharmaceuticals, Inc. | Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as pi3k kinase inhibitors |
| WO2017214269A1 (en) | 2016-06-08 | 2017-12-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| WO2017223422A1 (en) | 2016-06-24 | 2017-12-28 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| CA3102279A1 (en) | 2018-06-01 | 2019-12-05 | Cornell University | Combination therapy for pi3k-associated disease or disorder |
| WO2021165876A1 (en) * | 2020-02-19 | 2021-08-26 | Friedrich Miescher Institute For Biomedical Research | Novel therapeutical tools and methods using temperature-senstive receptors for treating blindness |
Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11501923A (ja) * | 1995-03-10 | 1999-02-16 | サノフィ ファーマシューティカルズ，インコーポレイティド | ６−置換ピラゾロ〔３，４−ｄ〕ピリミジン−４−オン並びにそれらを含有する組成物および使用方法 |
| JP2002537223A (ja) * | 1998-10-13 | 2002-11-05 | デュポン ファーマシューティカルズ カンパニー | サイクリン依存性キナーゼ阻害剤として有用な６−置換ピラゾロ［３，４−ｄ］ピリミジン−４−オン類 |
| JP2005509635A (ja) * | 2001-10-19 | 2005-04-14 | アイコス コーポレイション | 人間のホスファチジルイノシトール３−キナーゼデルタの阻害 |
| JP2005516000A (ja) * | 2001-12-06 | 2005-06-02 | メルク エンド カムパニー インコーポレーテッド | 有糸分裂キネシン阻害薬 |
| JP2005520793A (ja) * | 2001-12-06 | 2005-07-14 | メルク エンド カムパニー インコーポレーテッド | 有糸分裂キネシン阻害剤 |
| WO2005113556A1 (en) * | 2004-05-13 | 2005-12-01 | Icos Corporation | Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta |
| JP2005536475A (ja) * | 2002-05-23 | 2005-12-02 | サイトキネティクス・インコーポレーテッド | 化合物、組成物、および方法 |
| WO2006122200A1 (en) * | 2005-05-11 | 2006-11-16 | Merck Sharp & Dohme Limited | 2,3-substituted fused bicyclic pyrimidin-4(3h)-ones modulating the function of the vanilloid-1 receptor (vr1) |
| WO2007056846A1 (en) * | 2005-11-15 | 2007-05-24 | Merck Frosst Canada Ltd. | Azacyclohexane derivatives as inhibitors of stearoyl-coenzyme a delta-9 desaturase |
| JP2009537588A (ja) * | 2006-05-23 | 2009-10-29 | エフ．ホフマン−ラ ロシュ アーゲー | ピリドピリミジノン誘導体 |
| JP2010509373A (ja) * | 2006-11-13 | 2010-03-25 | イーライ リリー アンド カンパニー | 炎症性疾患および癌の処置のためのチエノピリミジノン |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4782137A (en) * | 1984-01-24 | 1988-11-01 | Immunex Corporation | Synthesis of protein with an identification peptide, and hybrid polypeptide incorporating same |
| US4703004A (en) * | 1984-01-24 | 1987-10-27 | Immunex Corporation | Synthesis of protein with an identification peptide |
| US4851341A (en) * | 1986-12-19 | 1989-07-25 | Immunex Corporation | Immunoaffinity purification system |
| US5011912A (en) * | 1986-12-19 | 1991-04-30 | Immunex Corporation | Hybridoma and monoclonal antibody for use in an immunoaffinity purification system |
| US5858753A (en) * | 1996-11-25 | 1999-01-12 | Icos Corporation | Lipid kinase |
| KR100785363B1 (ko) * | 2000-04-25 | 2007-12-18 | 이코스 코포레이션 | 인간 포스파티딜-이노시톨 3-키나제 델타의 억제제 |
| CZ20031910A3 (cs) * | 2000-12-11 | 2003-12-17 | Tularik Inc. | Sloučenina s antagonistickými účinky na CXCR3 a farmaceutický postředek |
| US6518227B2 (en) * | 2001-02-13 | 2003-02-11 | Robert Woosley | Solvent composition for denture adhesive |
| WO2005117889A1 (en) * | 2004-05-25 | 2005-12-15 | Icos Corporation | Methods for treating and/or preventing aberrant proliferation of hematopoietic |
| KR20070046176A (ko) * | 2004-08-18 | 2007-05-02 | 아스트라제네카 아베 | 특정 융합 피리미돈의 거울상이성질체 및 이의 암 치료 및예방에 있어서의 용도 |
| DE602006015658D1 (de) * | 2005-06-27 | 2010-09-02 | Amgen Inc | Entzündungshemmende arylnitrilverbindungen |
| CA2680783C (en) * | 2007-03-23 | 2012-04-24 | Amgen Inc. | Heterocyclic compounds and their uses |
-
2008
- 2008-11-12 EP EP08850176A patent/EP2220089A4/en not_active Withdrawn
- 2008-11-12 JP JP2010534149A patent/JP2011503193A/ja active Pending
- 2008-11-12 KR KR1020107013006A patent/KR20100119745A/ko not_active Withdrawn
- 2008-11-12 AU AU2008321099A patent/AU2008321099A1/en not_active Abandoned
- 2008-11-12 NZ NZ585460A patent/NZ585460A/xx not_active IP Right Cessation
- 2008-11-12 SG SG2012083556A patent/SG185996A1/en unknown
- 2008-11-12 GE GEAP200811842A patent/GEP20125635B/en unknown
- 2008-11-12 CN CN2008801245653A patent/CN101952292A/zh active Pending
- 2008-11-12 EA EA201070611A patent/EA201070611A1/ru unknown
- 2008-11-12 WO PCT/US2008/083262 patent/WO2009064802A2/en not_active Ceased
- 2008-11-12 US US12/742,904 patent/US20110021541A1/en not_active Abandoned
- 2008-11-12 CA CA2716334A patent/CA2716334A1/en not_active Abandoned
-
2010
- 2010-05-13 IL IL205747A patent/IL205747A0/en unknown
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH11501923A (ja) * | 1995-03-10 | 1999-02-16 | サノフィ ファーマシューティカルズ，インコーポレイティド | ６−置換ピラゾロ〔３，４−ｄ〕ピリミジン−４−オン並びにそれらを含有する組成物および使用方法 |
| JP2002537223A (ja) * | 1998-10-13 | 2002-11-05 | デュポン ファーマシューティカルズ カンパニー | サイクリン依存性キナーゼ阻害剤として有用な６−置換ピラゾロ［３，４−ｄ］ピリミジン−４−オン類 |
| JP2005509635A (ja) * | 2001-10-19 | 2005-04-14 | アイコス コーポレイション | 人間のホスファチジルイノシトール３−キナーゼデルタの阻害 |
| JP2005516000A (ja) * | 2001-12-06 | 2005-06-02 | メルク エンド カムパニー インコーポレーテッド | 有糸分裂キネシン阻害薬 |
| JP2005520793A (ja) * | 2001-12-06 | 2005-07-14 | メルク エンド カムパニー インコーポレーテッド | 有糸分裂キネシン阻害剤 |
| JP2005536475A (ja) * | 2002-05-23 | 2005-12-02 | サイトキネティクス・インコーポレーテッド | 化合物、組成物、および方法 |
| WO2005113556A1 (en) * | 2004-05-13 | 2005-12-01 | Icos Corporation | Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta |
| WO2006122200A1 (en) * | 2005-05-11 | 2006-11-16 | Merck Sharp & Dohme Limited | 2,3-substituted fused bicyclic pyrimidin-4(3h)-ones modulating the function of the vanilloid-1 receptor (vr1) |
| WO2007056846A1 (en) * | 2005-11-15 | 2007-05-24 | Merck Frosst Canada Ltd. | Azacyclohexane derivatives as inhibitors of stearoyl-coenzyme a delta-9 desaturase |
| JP2009537588A (ja) * | 2006-05-23 | 2009-10-29 | エフ．ホフマン−ラ ロシュ アーゲー | ピリドピリミジノン誘導体 |
| JP2010509373A (ja) * | 2006-11-13 | 2010-03-25 | イーライ リリー アンド カンパニー | 炎症性疾患および癌の処置のためのチエノピリミジノン |
Non-Patent Citations (1)
| Title |
|---|
| JPN6013044852; Ｊｏｕｒｎｎａｌ ｏｆ Ｍｅｄｉｃｉｎａｌ Ｃｈｅｍｉｓｔｒｙ Ｖｏｌ．４７， Ｎｏ．２４, 2004, ｐ．５８９４-５９１１ * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011508782A (ja) * | 2008-01-04 | 2011-03-17 | インテリカイン， インコーポレイテッド | 特定の化学的実体、組成物および方法 |
| JP2014520888A (ja) * | 2011-07-19 | 2014-08-25 | インフィニティー ファーマシューティカルズ， インコーポレイテッド | 複素環式化合物及びその使用 |
| JP2014520887A (ja) * | 2011-07-19 | 2014-08-25 | インフィニティー ファーマシューティカルズ， インコーポレイテッド | 複素環式化合物及びその使用 |
| JP2015509509A (ja) * | 2012-03-06 | 2015-03-30 | ベイジン ウェイフオン イーミーン バイオ−テクノロジー リミティドカンパニー | 慢性閉塞性疾患を治療するための医薬品組成物の製造のための、ルパタジンの使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2009064802A3 (en) | 2009-07-02 |
| SG185996A1 (en) | 2012-12-28 |
| NZ585460A (en) | 2013-02-22 |
| EP2220089A4 (en) | 2011-10-26 |
| EP2220089A2 (en) | 2010-08-25 |
| GEP20125635B (en) | 2012-09-10 |
| IL205747A0 (en) | 2010-11-30 |
| AU2008321099A1 (en) | 2009-05-22 |
| CA2716334A1 (en) | 2009-05-22 |
| EA201070611A1 (ru) | 2010-12-30 |
| KR20100119745A (ko) | 2010-11-10 |
| US20110021541A1 (en) | 2011-01-27 |
| CN101952292A (zh) | 2011-01-19 |
| WO2009064802A2 (en) | 2009-05-22 |
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