AU2012318694B2 - Novel imidazole quinoline-based immune system modulators - Google Patents
Novel imidazole quinoline-based immune system modulators Download PDFInfo
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- AU2012318694B2 AU2012318694B2 AU2012318694A AU2012318694A AU2012318694B2 AU 2012318694 B2 AU2012318694 B2 AU 2012318694B2 AU 2012318694 A AU2012318694 A AU 2012318694A AU 2012318694 A AU2012318694 A AU 2012318694A AU 2012318694 B2 AU2012318694 B2 AU 2012318694B2
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- heterocycle
- alkyl
- cycloalkyl
- optionally substituted
- heteroatoms
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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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 |
| JP6995109B2 (ja) | 2016-07-30 | 2022-01-14 | ブリストル－マイヤーズ スクイブ カンパニー | ジメトキシフェニル置換インドール化合物 |
| ES2902504T3 (es) | 2016-09-09 | 2022-03-28 | Bristol Myers Squibb Co | Compuestos de indol sustituidos con piridilo |
| KR102688509B1 (ko) | 2017-08-04 | 2024-07-24 | 브리스톨-마이어스 스큅 컴퍼니 | [1,2,4]트리아졸로[4,3-a]피리디닐 치환된 인돌 화합물 |
| ES2909401T3 (es) | 2017-08-04 | 2022-05-06 | Bristol Myers Squibb Co | Compuestos de indol sustituidos útiles como inhibidores de TLR7/8/9 |
| EP3710440B1 (en) | 2017-11-14 | 2023-04-05 | Bristol-Myers Squibb Company | Substituted indole compounds |
| CA3085333A1 (en) | 2017-12-15 | 2019-06-20 | Bristol-Myers Squibb Company | Substituted indole ether compounds |
| WO2019125977A1 (en) | 2017-12-18 | 2019-06-27 | Bristol-Myers Squibb Company | 4-azaindole compounds |
| KR102742178B1 (ko) | 2017-12-19 | 2024-12-12 | 브리스톨-마이어스 스큅 컴퍼니 | Tlr 억제제로서 유용한 치환된 인돌 화합물 |
| 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 |
| EP3728264B1 (en) | 2017-12-20 | 2021-12-01 | Bristol-Myers Squibb Company | Diazaindole compounds |
| AU2018393003A1 (en) | 2017-12-20 | 2020-08-06 | Bristol-Myers Squibb Company | Aryl and heteroaryl substituted indole compounds |
| CN111491929B (zh) | 2017-12-20 | 2023-11-28 | 百时美施贵宝公司 | 可用作tlr抑制剂的氨基吲哚化合物 |
| WO2020086503A1 (en) | 2018-10-24 | 2020-04-30 | Bristol-Myers Squibb Company | Substituted indole and indazole compounds |
| EP3870589B1 (en) | 2018-10-24 | 2023-09-06 | Bristol-Myers Squibb Company | Substituted indole dimer compounds |
| JP2022525216A (ja) * | 2019-03-15 | 2022-05-11 | バーディー バイオファーマシューティカルズ インコーポレイテッド | 癌の治療のための免疫調節組成物および方法 |
| US12187723B2 (en) | 2019-05-09 | 2025-01-07 | Bristol-Myers Squibb Company | Substituted benzimidazolone compounds |
| ES2965164T3 (es) | 2019-10-04 | 2024-04-11 | Bristol Myers Squibb Co | Compuestos de carbazol sustituidos |
| US11530218B2 (en) | 2020-01-20 | 2022-12-20 | Incyte Corporation | Spiro compounds as inhibitors of KRAS |
| US11739102B2 (en) | 2020-05-13 | 2023-08-29 | 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 |
| US11767320B2 (en) | 2020-10-02 | 2023-09-26 | Incyte Corporation | Bicyclic dione compounds as inhibitors of KRAS |
| US12077539B2 (en) | 2021-03-22 | 2024-09-03 | Incyte Corporation | Imidazole and triazole KRAS inhibitors |
| US11661431B2 (en) | 2021-04-16 | 2023-05-30 | Gilead Sciences, Inc. | Thienopyrrole compounds |
| CA3230800A1 (en) | 2021-09-10 | 2023-03-16 | Gilead Sciences, Inc. | Thienopyrrole compounds |
| WO2023049697A1 (en) | 2021-09-21 | 2023-03-30 | Incyte Corporation | Hetero-tricyclic compounds as inhibitors of kras |
| US12030884B2 (en) | 2021-10-01 | 2024-07-09 | Incyte Corporation | Pyrazoloquinoline KRAS inhibitors |
| AU2022367432A1 (en) | 2021-10-14 | 2024-05-02 | Incyte Corporation | Quinoline compounds as inhibitors of kras |
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 |
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| DE69535036T3 (de) | 1994-07-15 | 2011-07-07 | The University of Iowa Research Foundation, IA | Immunomodulatorische oligonukleotide |
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| 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. |
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| CA2283557A1 (en) | 1997-03-10 | 1998-09-17 | Heather L. Davis | Use of nucleic acids containing unmethylated cpg dinucleotide as an adjuvant |
| 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 |
| ATE370740T1 (de) | 1997-05-20 | 2007-09-15 | Ottawa Health Research Inst | Verfahren zur herstellung von nukleinsäurekonstrukten |
| US6218371B1 (en) | 1998-04-03 | 2001-04-17 | University Of Iowa Research Foundation | Methods and products for stimulating the immune system using immunotherapeutic oligonucleotides and cytokines |
| WO1999056755A1 (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 |
| DK1144388T3 (da) | 1999-01-22 | 2010-05-25 | Elan Pharm Inc | Acyl-derivater, som behandler VLA-4-relaterede lidelser |
| ES2265980T5 (es) | 1999-09-27 | 2010-12-28 | Coley Pharmaceutical Group, Inc. | Metodos relacionados con interferón inducido por ácidos nucleicos inmunoestimuladores. |
| CN1721443A (zh) | 2000-05-25 | 2006-01-18 | 先灵公司 | 人受体蛋白；相关的试剂和方法 |
| KR100991644B1 (ko) | 2001-08-17 | 2010-11-02 | 콜리 파마슈티칼 게엠베하 | 활성이 개량된 조합 모티프 면역자극성 올리고뉴클레오티드 |
| WO2005016235A2 (en) | 2003-04-14 | 2005-02-24 | The 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. |
| US8158794B2 (en) | 2005-02-23 | 2012-04-17 | 3M Innovative Properties Company | Hydroxyalkyl substituted imidazoquinoline compounds and methods |
| JP5247458B2 (ja) * | 2005-11-04 | 2013-07-24 | スリーエム・イノベイティブ・プロパティーズ・カンパニー | ヒドロキシ及びアルコキシ置換１ｈ−イミダゾキノリン及び方法 |
| 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 |
| EP3176169A1 (en) * | 2007-01-31 | 2017-06-07 | 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 |
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| 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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| CA2850932A1 (en) | 2013-04-11 |
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| US9873694B2 (en) | 2018-01-23 |
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