AU2008321099A1 - Inhibitors of human phosphatidyl-inositol 3-kinase delta - Google Patents
Inhibitors of human phosphatidyl-inositol 3-kinase delta Download PDFInfo
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- AU2008321099A1 AU2008321099A1 AU2008321099A AU2008321099A AU2008321099A1 AU 2008321099 A1 AU2008321099 A1 AU 2008321099A1 AU 2008321099 A AU2008321099 A AU 2008321099A AU 2008321099 A AU2008321099 A AU 2008321099A AU 2008321099 A1 AU2008321099 A1 AU 2008321099A1
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Families Citing this family (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030133939A1 (en) | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
| US7754208B2 (en) | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, 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 |
| 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 |
| DE10320785A1 (de) | 2003-05-09 | 2004-11-25 | Bayer Healthcare Ag | 6-Arylmethyl-substituierte Pyrazolopyrimidine |
| JP2008520744A (ja) | 2004-11-19 | 2008-06-19 | ザ・レジェンツ・オブ・ザ・ユニバーシティ・オブ・カリフォルニア | 抗炎症性ピラゾロピリミジン |
| SI1912675T1 (sl) | 2005-07-25 | 2014-07-31 | Emergent Product Development Seattle, Llc | zmanjšanje števila celic B z uporabo molekul, ki se specifično vežejo na CD37 in CD20 |
| AU2007347115A1 (en) | 2006-04-04 | 2008-10-23 | The Regents Of The University Of California | PI3 kinase antagonists |
| EP2418223A3 (en) | 2006-06-12 | 2013-01-16 | Emergent Product Development Seattle, LLC | Single-chain multivalent binding proteins with effector function |
| GB2467670B (en) | 2007-10-04 | 2012-08-01 | Intellikine Inc | Chemical entities and therapeutic uses thereof |
| DK2240451T3 (da) | 2008-01-04 | 2017-11-20 | Intellikine Llc | Isoquinolinonderivater substitueret med en purin, der er anvendelig som pi3k-inhibitorer |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| US8637542B2 (en) | 2008-03-14 | 2014-01-28 | Intellikine, Inc. | Kinase inhibitors and methods of use |
| US8993580B2 (en) | 2008-03-14 | 2015-03-31 | Intellikine Llc | Benzothiazole kinase inhibitors and methods of use |
| 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 |
| SG189772A1 (en) | 2008-04-11 | 2013-05-31 | Trubion Pharmaceuticals Inc | Cd37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof |
| 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 |
| CA2738429C (en) | 2008-09-26 | 2016-10-25 | Intellikine, Inc. | Heterocyclic kinase inhibitors |
| CA2740885C (en) | 2008-10-16 | 2018-04-03 | The Regents Of The University Of California | Fused ring heteroaryl kinase inhibitors |
| US8476282B2 (en) | 2008-11-03 | 2013-07-02 | Intellikine Llc | Benzoxazole kinase inhibitors and methods of use |
| DK2414363T3 (da) | 2009-03-31 | 2014-01-27 | Boehringer Ingelheim Int | 1-heterocyklyl-1,5-dihydro-pyrazol[3,4-d]pyrimidin-4-on-derivater og anvendelse af disse som PDE9A-modulatorer. |
| EP2427195B1 (en) | 2009-05-07 | 2019-05-01 | Intellikine, LLC | Heterocyclic compounds and uses thereof |
| CN102573846B (zh) | 2009-08-17 | 2015-10-07 | 因特利凯公司 | 杂环化合物及其用途 |
| WO2011047384A2 (en) | 2009-10-16 | 2011-04-21 | The Regents Of The University Of California | Methods of inhibiting ire1 |
| AU2011255218B2 (en) | 2010-05-21 | 2015-03-12 | Infinity Pharmaceuticals, Inc. | Chemical compounds, compositions and methods for kinase modulation |
| EP3399026B1 (en) | 2010-06-14 | 2024-06-26 | The Scripps Research Institute | Reprogramming of cells to a new fate |
| AU2011326427B2 (en) | 2010-11-10 | 2016-01-07 | Infinity Pharmaceuticals Inc. | Heterocyclic compounds and uses thereof |
| PE20180318A1 (es) | 2011-01-10 | 2018-02-09 | Infinity Pharmaceuticals Inc | Procedimiento para preparar isoquinolinonas y formas solidas de isoquinolinonas |
| JP6130305B2 (ja) | 2011-02-23 | 2017-05-17 | インテリカイン， エルエルシー | キナーゼ阻害剤の組み合わせおよびそれらの使用 |
| WO2013012918A1 (en) * | 2011-07-19 | 2013-01-24 | Infinity Pharmaceuticals Inc. | Heterocyclic compounds and uses thereof |
| WO2013012915A1 (en) * | 2011-07-19 | 2013-01-24 | Infinity Pharmaceuticals Inc. | Heterocyclic compounds and uses thereof |
| AR091790A1 (es) | 2011-08-29 | 2015-03-04 | Infinity Pharmaceuticals Inc | Derivados de isoquinolin-1-ona y sus usos |
| JP6342805B2 (ja) | 2011-09-02 | 2018-06-13 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 置換ピラゾロ［３，４−ｄ］ピリミジンおよびその用途 |
| DK2790705T3 (en) | 2011-12-15 | 2018-03-12 | Novartis Ag | Use of inhibitors of the activity or function of PI3K |
| CN102614177B (zh) * | 2012-03-06 | 2014-08-06 | 北京伟峰益民科技有限公司 | 卢帕他定在制备治疗慢性阻塞性肺病药物组合物中的应用 |
| MX2014011115A (es) | 2012-03-16 | 2015-03-13 | Axikin Pharmaceuticals Inc | Inhibidores de 3,5-diaminopirazol cinasa. |
| US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| US8828998B2 (en) | 2012-06-25 | 2014-09-09 | Infinity Pharmaceuticals, Inc. | Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors |
| CN104768952B (zh) * | 2012-08-08 | 2016-10-19 | 山东亨利医药科技有限责任公司 | PI3Kδ抑制剂 |
| KR20150061651A (ko) | 2012-09-26 | 2015-06-04 | 더 리젠츠 오브 더 유니버시티 오브 캘리포니아 | Ire1의 조절 |
| LT2914296T (lt) | 2012-11-01 | 2018-09-25 | Infinity Pharmaceuticals, Inc. | Vėžio gydymas, panaudojant p13 kinazės izoformos moduliatorius |
| US9737521B2 (en) | 2012-11-08 | 2017-08-22 | Rhizen Pharmaceuticals Sa | Pharmaceutical compositions containing a PDE4 inhibitor and a PI3 delta or dual PI3 delta-gamma kinase inhibitor |
| US9481667B2 (en) | 2013-03-15 | 2016-11-01 | Infinity Pharmaceuticals, Inc. | Salts and solid forms of isoquinolinones and composition comprising and methods of using the same |
| JP6360881B2 (ja) | 2013-03-22 | 2018-07-18 | ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | 触媒的ｍｔｏｒｃ１／２阻害薬及びオーロラａキナーゼの選択的阻害薬の組合せ |
| NZ631142A (en) | 2013-09-18 | 2016-03-31 | Axikin Pharmaceuticals Inc | Pharmaceutically acceptable salts of 3,5-diaminopyrazole kinase inhibitors |
| CA2920059A1 (en) | 2013-09-22 | 2015-03-26 | Calitor Sciences, Llc | Substituted aminopyrimidine compounds and methods of use |
| US9751888B2 (en) | 2013-10-04 | 2017-09-05 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| WO2015051244A1 (en) | 2013-10-04 | 2015-04-09 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| EP3119397B1 (en) | 2014-03-19 | 2022-03-09 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds for use in the treatment of pi3k-gamma mediated disorders |
| US20150320755A1 (en) | 2014-04-16 | 2015-11-12 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| MA40250A (fr) | 2014-07-04 | 2017-05-10 | Lupin Ltd | Dérivés de quinolizinone utilisés comme inhibiteurs 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 |
| US9637488B2 (en) | 2015-01-29 | 2017-05-02 | Fuqiang Ruan | Heterocyclic compounds as inhibitors of class I PI3KS |
| CN114230571B (zh) | 2015-09-14 | 2025-07-08 | 无限药品股份有限公司 | 异喹啉酮的固体形式、其制备方法、包含其的组合物及其使用方法 |
| UA126278C2 (uk) | 2015-09-21 | 2022-09-14 | Аптево Рісьорч Енд Девелопмент Ллс | Поліпептиди, які зв'язують cd3 |
| 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 |
| US10759806B2 (en) | 2016-03-17 | 2020-09-01 | Infinity Pharmaceuticals, Inc. | Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as PI3K kinase inhibitors |
| US10919914B2 (en) | 2016-06-08 | 2021-02-16 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| UA125216C2 (uk) | 2016-06-24 | 2022-02-02 | Інфініті Фармасьютікалз, Інк. | Комбінована терапія |
| CN113194752A (zh) | 2018-06-01 | 2021-07-30 | 康奈尔大学 | Pi3k相关疾病或病症的组合疗法 |
| US20230103783A1 (en) * | 2020-02-19 | 2023-04-06 | Friedrich Miescher Institute For Biomedical Research | Novel therapeutical tools and methods using temperature-sensitive receptors for treating blindness |
Family Cites Families (23)
| 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 |
| US5656629A (en) * | 1995-03-10 | 1997-08-12 | Sanofi Winthrop, Inc. | 6-substituted pyrazolo (3,4-d)pyrimidin-4-ones and compositions and methods of use thereof |
| US5858753A (en) * | 1996-11-25 | 1999-01-12 | Icos Corporation | Lipid kinase |
| US6531477B1 (en) * | 1998-10-13 | 2003-03-11 | Dupont Pharmaceuticals Company | 6-substituted pyrazolo [3,4-d] pyrimidin-4-ones useful as cyclin dependent kinase inhibitors |
| EP1278748B1 (en) * | 2000-04-25 | 2011-03-23 | ICOS Corporation | Inhibitors of human phosphatidyl-inositol 3-kinase delta |
| US6667300B2 (en) * | 2000-04-25 | 2003-12-23 | Icos Corporation | Inhibitors of human phosphatidylinositol 3-kinase delta |
| KR100883184B1 (ko) * | 2000-12-11 | 2009-02-12 | 암젠 인코포레이션 | Ｃｘｃｒ3 길항제 |
| US6518227B2 (en) * | 2001-02-13 | 2003-02-11 | Robert Woosley | Solvent composition for denture adhesive |
| JP4467979B2 (ja) * | 2001-12-06 | 2010-05-26 | メルク・シャープ・エンド・ドーム・コーポレイション | 有糸分裂キネシン阻害剤 |
| WO2003049527A2 (en) * | 2001-12-06 | 2003-06-19 | Merck & Co., Inc. | Mitotic kinesin inhibitors |
| WO2003103575A2 (en) * | 2002-05-23 | 2003-12-18 | Cytokinetics, Inc. | Compounds, compositions, and methods |
| RS55546B1 (sr) * | 2004-05-13 | 2017-05-31 | Icos Corp | Hinazolinoni kao inhibitori humane fosfatidilonozitol 3-delta kinaze |
| WO2005117889A1 (en) * | 2004-05-25 | 2005-12-15 | Icos Corporation | Methods for treating and/or preventing aberrant proliferation of hematopoietic |
| MY141233A (en) * | 2004-08-18 | 2010-03-31 | Astrazeneca Ab | Enantiomers of selected fused heterocyclics and uses thereof |
| CA2607929A1 (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) |
| ATE474829T1 (de) * | 2005-06-27 | 2010-08-15 | Amgen Inc | Entzündungshemmende arylnitrilverbindungen |
| EP1951731A4 (en) * | 2005-11-15 | 2010-07-07 | Merck Frosst Canada Ltd | AZACYCLOHEXANDERIVATES AS INHIBITORS OF STEAROYL-COENZYME-A-DELTA-9-DESATURASE |
| ATE469905T1 (de) * | 2006-05-23 | 2010-06-15 | Hoffmann La Roche | Pyridopyrimidinonderivate |
| CA2669399A1 (en) * | 2006-11-13 | 2008-05-29 | Eli Lilly & Co. | Thienopyrimidinones for treatment of inflammatory disorders and cancers |
| EP2132207A2 (en) * | 2007-03-23 | 2009-12-16 | Amgen Inc. | Heterocyclic compounds and their uses |
-
2008
- 2008-11-12 GE GEAP200811842A patent/GEP20125635B/en unknown
- 2008-11-12 NZ NZ585460A patent/NZ585460A/xx not_active IP Right Cessation
- 2008-11-12 EP EP08850176A patent/EP2220089A4/en not_active Withdrawn
- 2008-11-12 EA EA201070611A patent/EA201070611A1/ru unknown
- 2008-11-12 SG SG2012083556A patent/SG185996A1/en unknown
- 2008-11-12 KR KR1020107013006A patent/KR20100119745A/ko not_active Withdrawn
- 2008-11-12 JP JP2010534149A patent/JP2011503193A/ja active Pending
- 2008-11-12 US US12/742,904 patent/US20110021541A1/en not_active Abandoned
- 2008-11-12 CN CN2008801245653A patent/CN101952292A/zh active Pending
- 2008-11-12 AU AU2008321099A patent/AU2008321099A1/en not_active Abandoned
- 2008-11-12 WO PCT/US2008/083262 patent/WO2009064802A2/en not_active Ceased
- 2008-11-12 CA CA2716334A patent/CA2716334A1/en not_active Abandoned
-
2010
- 2010-05-13 IL IL205747A patent/IL205747A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| GEP20125635B (en) | 2012-09-10 |
| EP2220089A2 (en) | 2010-08-25 |
| WO2009064802A2 (en) | 2009-05-22 |
| CN101952292A (zh) | 2011-01-19 |
| SG185996A1 (en) | 2012-12-28 |
| WO2009064802A3 (en) | 2009-07-02 |
| NZ585460A (en) | 2013-02-22 |
| CA2716334A1 (en) | 2009-05-22 |
| EA201070611A1 (ru) | 2010-12-30 |
| KR20100119745A (ko) | 2010-11-10 |
| IL205747A0 (en) | 2010-11-30 |
| EP2220089A4 (en) | 2011-10-26 |
| US20110021541A1 (en) | 2011-01-27 |
| JP2011503193A (ja) | 2011-01-27 |
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Legal Events
| Date | Code | Title | Description |
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| MK4 | Application lapsed section 142(2)(d) - no continuation fee paid for the application |