CA2850932A1 - Novel imidazole quinoline-based immune system modulators - Google Patents
Novel imidazole quinoline-based immune system modulators Download PDFInfo
- Publication number
- CA2850932A1 CA2850932A1 CA2850932A CA2850932A CA2850932A1 CA 2850932 A1 CA2850932 A1 CA 2850932A1 CA 2850932 A CA2850932 A CA 2850932A CA 2850932 A CA2850932 A CA 2850932A CA 2850932 A1 CA2850932 A1 CA 2850932A1
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- Prior art keywords
- alkyl
- heterocycle
- optionally substituted
- cycloalkyl
- heteroatoms
- Prior art date
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- Abandoned
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| PCT/US2012/058566 WO2013052550A2 (en) | 2011-10-04 | 2012-10-03 | Novel imidazole quinoline-based immune system modulators |
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| US9227969B2 (en) | 2013-08-14 | 2016-01-05 | Novartis Ag | Compounds and compositions as inhibitors of MEK |
| US10071079B2 (en) | 2016-06-29 | 2018-09-11 | Bristol-Myers Squibb Company | [1,2,4]triazolo[1,5-a]pyridinyl substituted indole compounds |
| MX391344B (es) | 2016-07-30 | 2025-03-21 | Bristol Myers Squibb Co | Compuestos indol sustituidos con dimetoxifenilo como inhibidores de receptores tipo toll 7, 8 o 9 (tlr7, tlr8 o tlr9). |
| MA46188A (fr) | 2016-09-09 | 2019-07-17 | Bristol Myers Squibb Co | Composés indole substitués par pyridyle |
| US11130756B2 (en) | 2017-08-04 | 2021-09-28 | Bristol-Myers Squibb Company | [1,2,4]Triazolo[4,3-A]pyridinyl substituted indole compounds |
| EP3661926B1 (en) | 2017-08-04 | 2022-02-23 | Bristol-Myers Squibb Company | Substituted indole compounds useful as inhibitors of tlr7/8/9 |
| WO2019099336A1 (en) | 2017-11-14 | 2019-05-23 | Bristol-Myers Squibb Company | Substituted indole compounds |
| WO2019118799A1 (en) | 2017-12-15 | 2019-06-20 | Bristol-Myers Squibb Company | Substituted indole ether compounds |
| US10544143B2 (en) | 2017-12-18 | 2020-01-28 | Bristol-Myers Squibb Company | 4-azaindole compounds |
| ES2932361T3 (es) | 2017-12-19 | 2023-01-18 | Bristol Myers Squibb Co | Compuestos de indol sustituidos útiles como inhibidores de TLR |
| JP7313354B2 (ja) | 2017-12-19 | 2023-07-24 | ブリストル－マイヤーズ スクイブ カンパニー | Ｔｌｒ阻害剤として有用なアミド置換されたインドール化合物 |
| AU2018390543A1 (en) | 2017-12-19 | 2020-08-06 | Bristol-Myers Squibb Company | 6-azaindole compounds |
| SG11202005733QA (en) | 2017-12-20 | 2020-07-29 | Bristol Myers Squibb Co | Diazaindole compounds |
| US11306092B2 (en) | 2017-12-20 | 2022-04-19 | Bristol-Myers Squibb Company | Amino indole compounds useful as TLR inhibitors |
| SG11202005695PA (en) | 2017-12-20 | 2020-07-29 | Bristol Myers Squibb Co | Aryl and heteroaryl substituted indole compounds |
| EP3870583A1 (en) | 2018-10-24 | 2021-09-01 | Bristol-Myers Squibb Company | Substituted indole and indazole compounds |
| US11998537B2 (en) | 2018-10-24 | 2024-06-04 | Bristol-Myers Squibb Company | Substituted indole dimer compounds |
| WO2020190690A1 (en) * | 2019-03-15 | 2020-09-24 | Birdie Biopharmaceuticals, Inc. | Immune modulatory compositions and methods for treating cancers |
| CN114126713B (zh) | 2019-05-09 | 2023-12-08 | 百时美施贵宝公司 | 经取代的苯并咪唑酮化合物 |
| JP7545467B2 (ja) | 2019-10-04 | 2024-09-04 | ブリストル－マイヤーズ スクイブ カンパニー | 置換カルバゾール化合物 |
| US11530218B2 (en) | 2020-01-20 | 2022-12-20 | Incyte Corporation | Spiro compounds as inhibitors of KRAS |
| WO2021231526A1 (en) | 2020-05-13 | 2021-11-18 | Incyte Corporation | Fused pyrimidine compounds as kras inhibitors |
| US11999752B2 (en) | 2020-08-28 | 2024-06-04 | Incyte Corporation | Vinyl imidazole compounds as inhibitors of KRAS |
| WO2022072783A1 (en) | 2020-10-02 | 2022-04-07 | Incyte Corporation | Bicyclic dione compounds as inhibitors of kras |
| US12077539B2 (en) | 2021-03-22 | 2024-09-03 | Incyte Corporation | Imidazole and triazole KRAS inhibitors |
| TWI861488B (zh) | 2021-04-16 | 2024-11-11 | 美商基利科學股份有限公司 | 噻吩并吡咯化合物 |
| JP2024533374A (ja) | 2021-09-10 | 2024-09-12 | ギリアード サイエンシーズ， インコーポレイテッド | チエノピロール化合物 |
| WO2023049697A1 (en) | 2021-09-21 | 2023-03-30 | Incyte Corporation | Hetero-tricyclic compounds as inhibitors of kras |
| EP4408536A1 (en) | 2021-10-01 | 2024-08-07 | Incyte Corporation | Pyrazoloquinoline kras inhibitors |
| JP2024539651A (ja) | 2021-10-14 | 2024-10-29 | インサイト・コーポレイション | Ｋｒａｓの阻害剤としてのキノリン化合物 |
Family Cites Families (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3854480A (en) | 1969-04-01 | 1974-12-17 | Alza Corp | Drug-delivery system |
| US4452775A (en) | 1982-12-03 | 1984-06-05 | Syntex (U.S.A.) Inc. | Cholesterol matrix delivery system for sustained release of macromolecules |
| CA1271477A (en) * | 1983-11-18 | 1990-07-10 | John F. Gerster | 1h-imidazo[4,5-c]quinolin-4-amines |
| US5075109A (en) | 1986-10-24 | 1991-12-24 | Southern Research Institute | Method of potentiating an immune response |
| US5133974A (en) | 1989-05-05 | 1992-07-28 | Kv Pharmaceutical Company | Extended release pharmaceutical formulations |
| US5407686A (en) | 1991-11-27 | 1995-04-18 | Sidmak Laboratories, Inc. | Sustained release composition for oral administration of active ingredient |
| US5491084A (en) | 1993-09-10 | 1996-02-13 | The Trustees Of Columbia University In The City Of New York | Uses of green-fluorescent protein |
| US6239116B1 (en) | 1994-07-15 | 2001-05-29 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| US6207646B1 (en) | 1994-07-15 | 2001-03-27 | University Of Iowa Research Foundation | Immunostimulatory nucleic acid molecules |
| AU713040B2 (en) | 1994-07-15 | 1999-11-18 | University Of Iowa Research Foundation, The | Immunomodulatory oligonucleotides |
| US5736152A (en) | 1995-10-27 | 1998-04-07 | Atrix Laboratories, Inc. | Non-polymeric sustained release delivery system |
| AR006928A1 (es) | 1996-05-01 | 1999-09-29 | Pioneer Hi Bred Int | Una molecula de adn aislada que codifica una proteina fluorescente verde como marcador rastreable para la transformacion de plantas, un metodo para laproduccion de plantas transgenicas, un vector de expresion, una planta transgenica y celulas de dichas plantas. |
| WO1998037919A1 (en) | 1997-02-28 | 1998-09-03 | University Of Iowa Research Foundation | USE OF NUCLEIC ACIDS CONTAINING UNMETHYLATED CpG DINUCLEOTIDE IN THE TREATMENT OF LPS-ASSOCIATED DISORDERS |
| PT1005368E (pt) | 1997-03-10 | 2009-11-19 | Coley Pharm Gmbh | Utilização de ácidos nucleicos contendo dinucleótidos cpg não metilados em combinação com alúmen como adjuvante |
| CN101486759A (zh) | 1997-05-07 | 2009-07-22 | 先灵公司 | 人Toll样受体蛋白、相关试剂和方法 |
| AU7690898A (en) | 1997-05-20 | 1998-12-11 | Ottawa Civic Hospital Loeb Research Institute | Vectors and methods for immunization or therapeutic protocols |
| CA2323929C (en) | 1998-04-03 | 2004-03-09 | University Of Iowa Research Foundation | Methods and products for stimulating the immune system using immunotherapeutic oligonucleotides and cytokines |
| CA2328602A1 (en) | 1998-05-06 | 1999-11-11 | University Of Iowa Research Foundation | Methods for the prevention and treatment of parasitic infections and related diseases using cpg oligonucleotides |
| JP2000119271A (ja) * | 1998-08-12 | 2000-04-25 | Hokuriku Seiyaku Co Ltd | １ｈ―イミダゾピリジン誘導体 |
| HK1046132B (zh) | 1999-01-22 | 2006-05-04 | 依兰制药公司 | 用於治疗与vla-4有关的疾病的酰基衍生物 |
| WO2001022990A2 (en) | 1999-09-27 | 2001-04-05 | Coley Pharmaceutical Group, Inc. | Methods related to immunostimulatory nucleic acid-induced interferon |
| EP1283849A2 (en) | 2000-05-25 | 2003-02-19 | Schering Corporation | Human receptor proteins; related reagents and methods |
| PT1446162E (pt) | 2001-08-17 | 2009-01-27 | Coley Pharm Gmbh | Agrupamentos imunoestimuladores oligonucléotidos com actividade melhorada |
| US20050004144A1 (en) | 2003-04-14 | 2005-01-06 | Regents Of The University Of California | Combined use of IMPDH inhibitors with toll-like receptor agonists |
| MXPA05013922A (es) * | 2003-06-20 | 2006-02-24 | Coley Pharm Group Inc | Antagonistas de receptor tipo toll de molecula pequena. |
| WO2006091567A2 (en) | 2005-02-23 | 2006-08-31 | Coley Pharmaceutical Group, Inc. | Hydroxyalkyl substituted imidazoquinoline compounds and methods |
| EP1948173B1 (en) * | 2005-11-04 | 2013-07-17 | 3M Innovative Properties Company | Hydroxy and alkoxy substituted 1h-imidazoquinolines and methods |
| EP2010530A2 (en) * | 2006-03-23 | 2009-01-07 | Novartis AG | Methods for the preparation of imidazole-containing compounds |
| US8027888B2 (en) * | 2006-08-31 | 2011-09-27 | Experian Interactive Innovation Center, Llc | Online credit card prescreen systems and methods |
| US20080149123A1 (en) * | 2006-12-22 | 2008-06-26 | Mckay William D | Particulate material dispensing hairbrush with combination bristles |
| US7943771B2 (en) * | 2007-01-24 | 2011-05-17 | Chemagis Ltd. | Imiquimod production process |
| EP2115140B8 (en) * | 2007-01-31 | 2017-01-25 | Chongxi Yu | Positively charged water-soluble prodrugs of 1H-imidazo[4,5-c]quinolin-4-amines and related compounds with very high skin penetration rates |
| EP1972629A1 (en) | 2007-03-23 | 2008-09-24 | Mutabilis SA | New imidazolo-heteroaryl derivatives with antibacterial properties |
| US20100120741A1 (en) * | 2008-09-10 | 2010-05-13 | Kalypsys, Inc. | Heterocyclic inhibitors of histamine receptors for the treatment of disease |
| WO2011068233A1 (en) * | 2009-12-03 | 2011-06-09 | Dainippon Sumitomo Pharma Co., Ltd. | Imidazoquinolines which act via toll - like receptors (tlr) |
| US8728486B2 (en) * | 2011-05-18 | 2014-05-20 | University Of Kansas | Toll-like receptor-7 and -8 modulatory 1H imidazoquinoline derived compounds |
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| AU2012318694A1 (en) | 2014-05-22 |
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| EP2763677A2 (en) | 2014-08-13 |
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| US9873694B2 (en) | 2018-01-23 |
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