JP7098716B2 - Jakキナーゼ阻害剤としてのピラゾロおよびトリアゾロ二環式化合物 - Google Patents
Jakキナーゼ阻害剤としてのピラゾロおよびトリアゾロ二環式化合物 Download PDFInfo
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- JP7098716B2 JP7098716B2 JP2020505224A JP2020505224A JP7098716B2 JP 7098716 B2 JP7098716 B2 JP 7098716B2 JP 2020505224 A JP2020505224 A JP 2020505224A JP 2020505224 A JP2020505224 A JP 2020505224A JP 7098716 B2 JP7098716 B2 JP 7098716B2
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| WO2013060636A1 (en) | 2011-10-25 | 2013-05-02 | Sanofi | 6-(4-hydroxy-phenyl)-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| WO2016178110A1 (en) | 2015-05-01 | 2016-11-10 | Pfizer Inc. | Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl, pyrrolo[2,3-b]pyridinyl acrylamides and epoxides thereof |
| JP2016539137A (ja) | 2013-12-05 | 2016-12-15 | ファイザー・インク | ピロロ[2,3−d]ピリミジニル、ピロロ[2,3−b]ピラジニル、およびピロロ[2,3−d]ピリジニルアクリルアミド |
| JP2017515836A (ja) | 2014-05-14 | 2017-06-15 | ファイザー・インク | ピラゾロピリジンおよびピラゾロピリミジン |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2444036A1 (en) | 2001-04-20 | 2002-10-31 | Yanfang Li | Heterocyclylalkoxy-, -alkylthio- and -alkylaminobenzazole derivatives as 5-hydroxytryptamine-6 ligands |
| FR2836915B1 (fr) | 2002-03-11 | 2008-01-11 | Aventis Pharma Sa | Derives d'aminoindazoles, procede de preparation et intermediaires de ce procede a titre de medicaments et compositions pharmaceutiques les renfermant |
| US20030139427A1 (en) * | 2002-08-23 | 2003-07-24 | Osi Pharmaceuticals Inc. | Bicyclic pyrimidinyl derivatives and methods of use thereof |
| JP4810427B2 (ja) | 2003-05-22 | 2011-11-09 | アボット・ラボラトリーズ | インダゾール、ベンズイソオキサゾールおよびベンズイソチアゾールキナーゼ阻害剤 |
| EP1647549A1 (en) | 2004-10-14 | 2006-04-19 | Laboratoire Theramex | Indazoles, benzisoxazoles and benzisothiazoles as estrogenic agents |
| CA2626579A1 (en) | 2005-10-25 | 2007-05-03 | Abbott Laboratories | Formulation comprising a drug of low water solubility and method of use thereof |
| EP1999135A2 (en) | 2006-03-30 | 2008-12-10 | Takeda San Diego, Inc. | Kinase inhibitors |
| KR100834758B1 (ko) | 2006-07-05 | 2008-06-05 | 삼성전자주식회사 | 컴퓨터 시스템 보안 장치 및 방법 |
| JP2009007342A (ja) | 2007-06-01 | 2009-01-15 | Mitsubishi Tanabe Pharma Corp | 医薬組成物 |
| US8648069B2 (en) | 2007-06-08 | 2014-02-11 | Abbvie Inc. | 5-substituted indazoles as kinase inhibitors |
| ES2445199T3 (es) | 2008-06-05 | 2014-02-28 | Glaxo Group Limited | Derivados de benzpirazol como inhibidores de PI3-quinasas |
| ATE552255T1 (de) | 2008-06-05 | 2012-04-15 | Glaxo Group Ltd | 4-aminoindazole |
| ES2526966T3 (es) | 2008-06-05 | 2015-01-19 | Glaxo Group Limited | Compuestos novedosos |
| JP2011529090A (ja) | 2008-07-28 | 2011-12-01 | 江蘇国華投資有限公司 | アラルキルピペリジン(又はピペラジン)誘導体及びその統合失調症治療のための使用 |
| TW201111385A (en) | 2009-08-27 | 2011-04-01 | Biocryst Pharm Inc | Heterocyclic compounds as janus kinase inhibitors |
| FR2951172B1 (fr) | 2009-10-13 | 2014-09-26 | Pf Medicament | Derives pyrazolopyridines en tant qu'agent anticancereux |
| EP2507226A1 (en) | 2009-12-03 | 2012-10-10 | Glaxo Group Limited | Novel compounds |
| EP2507223A1 (en) | 2009-12-03 | 2012-10-10 | Glaxo Group Limited | Benzpyrazole derivatives as inhibitors of p13 kinases |
| TW201200518A (en) | 2010-03-10 | 2012-01-01 | Kalypsys Inc | Heterocyclic inhibitors of histamine receptors for the treatment of disease |
| CN103370076A (zh) | 2010-11-02 | 2013-10-23 | 纽约市哥伦比亚大学托管会 | 治疗毛发脱落疾病的方法 |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| US8846712B2 (en) | 2011-09-12 | 2014-09-30 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| CN102993201A (zh) * | 2011-09-14 | 2013-03-27 | 赛诺菲 | 作为激酶抑制剂的6-(4-羟基-苯基)-3-苯乙烯基-1H-吡唑并[3,4-b]吡啶-4-羧酸酰胺衍生物 |
| WO2013045413A1 (en) | 2011-09-27 | 2013-04-04 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| US20130102601A1 (en) | 2011-10-21 | 2013-04-25 | F. Hoffmann-La Roche Ltd | Pyrimidin-4-one derivatives and their use in the treatment, amelioration or prevention of a viral disease |
| US8993756B2 (en) * | 2011-12-06 | 2015-03-31 | Merck Sharp & Dohme Corp. | Pyrrolopyrimidines as janus kinase inhibitors |
| US8377946B1 (en) * | 2011-12-30 | 2013-02-19 | Pharmacyclics, Inc. | Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors |
| CN104334191A (zh) | 2012-03-29 | 2015-02-04 | 纽约市哥伦比亚大学托管会 | 治疗毛发脱落疾病的方法 |
| EP2847191B1 (en) | 2012-05-09 | 2016-06-15 | Sanofi | Substituted 6-(4-hydroxy-phenyl)-1h-pyrazolo[3,4-b]pyridine derivatives as kinase inhibitors |
| TWI629275B (zh) | 2013-03-13 | 2018-07-11 | 賽諾菲公司 | N-(4-(氮雜吲唑-6-基)-苯基)-磺醯胺及其作為醫藥之用途 |
| JP2016113366A (ja) * | 2013-03-29 | 2016-06-23 | 大鵬薬品工業株式会社 | アセトアミド基を有する1,2,4−トリアジン−6−カルボキサミド誘導体 |
| WO2015112445A1 (en) | 2014-01-24 | 2015-07-30 | Abbvie Inc. | 6-phenyl- or 6-(pyridin-3-yl)indazole derivatives and methods of use |
| ES2921874T3 (es) * | 2014-02-28 | 2022-09-01 | Nimbus Lakshmi Inc | Inhibidores de TYK2 y usos de los mismos |
| US10519160B2 (en) | 2014-07-18 | 2019-12-31 | The General Hospital Corporation | Imaging agents for neural flux |
| US10590086B2 (en) | 2014-11-03 | 2020-03-17 | Iomet Pharma Ltd. | Pharmaceutical compound |
| CN105837574B (zh) | 2015-02-02 | 2018-03-02 | 四川大学 | N‑(3‑哌啶基)‑芳香胺衍生物及其制备方法和用途 |
| EP3291794A4 (en) | 2015-05-07 | 2019-02-13 | The Trustees of Columbia University in the City of New York | PROCEDURE AND COMPOSITIONS FOR PROMOTING HAIR GROWTH |
| DK3712152T3 (da) | 2015-11-03 | 2021-03-22 | Topivert Pharma Ltd | 4,5,6,7-tetrahydro-1h-imidazo[4,5-c]pyridin og 1,4,5,6,7,8-hexahydroimidazo[4,5-d]azepinderivater som janus kinase-inhibitorer |
| US10973913B2 (en) | 2016-02-16 | 2021-04-13 | Washington University | JAK inhibitors and uses thereof |
| CN109311896B (zh) | 2016-06-30 | 2021-08-24 | 株式会社大熊制药 | 吡唑并嘧啶衍生物作为激酶抑制剂 |
| US9956158B2 (en) | 2016-09-08 | 2018-05-01 | Synergistic Therapeutics, Llc | Topical hair growth formulation |
| EP3528816A4 (en) | 2016-10-21 | 2020-04-08 | Nimbus Lakshmi, Inc. | TYK2 INHIBITORS AND USES THEREOF |
| US20180117148A1 (en) | 2016-10-28 | 2018-05-03 | Andrew J. Holman | Compounds, pharmaceutical compositions and methods of treatments of immune related diseases and disorders |
| KR102032418B1 (ko) * | 2017-06-15 | 2019-10-16 | 한국화학연구원 | 접합 피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 포함하는 브루톤티로신 키나제 활성 관련 질환의 예방 또는 치료용 약학적 조성물 |
| BR112020002265A2 (pt) | 2017-08-01 | 2020-07-28 | Theravance Biopharma R&D Ip, Llc | compostos pirazólicos e triazólicos bicíclicos como inibidores de jak quiinase |
| SG11202002947TA (en) | 2017-11-03 | 2020-04-29 | Aclaris Therapeutics Inc | Substituted pyrrolopyrimidine jak inhibitors and methods of making and using the same |
| KR102577242B1 (ko) | 2017-12-28 | 2023-09-11 | 주식회사 대웅제약 | 카이네이즈 저해제로서의 아미노-메틸피페리딘 유도체 |
| TN2020000082A1 (en) | 2017-12-28 | 2022-01-06 | Dae Woong Pharma | Oxy-fluoropiperidine derivative as kinase inhibitor |
| KR102577241B1 (ko) | 2017-12-28 | 2023-09-11 | 주식회사 대웅제약 | 카이네이즈 저해제로서의 아미노-플루오로피페리딘 유도체 |
| JP2022518741A (ja) * | 2019-01-23 | 2022-03-16 | セラヴァンス バイオファーマ アール&ディー アイピー, エルエルシー | JAKキナーゼ阻害剤としてのイミダゾ[1,5-a]ピリジン、1,2,4-トリアゾロ[4,3-a]ピリジンおよびイミダゾ[1,5-a]ピラジン |
| EP4149462A4 (en) * | 2020-05-14 | 2024-04-24 | Theravance Biopharma R&D IP, LLC | Administration of gut-selective jak3 inhibitor |
-
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- 2021-03-17 JP JP2021043173A patent/JP2021098751A/ja not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013060636A1 (en) | 2011-10-25 | 2013-05-02 | Sanofi | 6-(4-hydroxy-phenyl)-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| JP2016539137A (ja) | 2013-12-05 | 2016-12-15 | ファイザー・インク | ピロロ[2,3−d]ピリミジニル、ピロロ[2,3−b]ピラジニル、およびピロロ[2,3−d]ピリジニルアクリルアミド |
| JP2017515836A (ja) | 2014-05-14 | 2017-06-15 | ファイザー・インク | ピラゾロピリジンおよびピラゾロピリミジン |
| WO2016178110A1 (en) | 2015-05-01 | 2016-11-10 | Pfizer Inc. | Pyrrolo[2,3-d]pyrimidinyl, pyrrolo[2,3-b]pyrazinyl, pyrrolo[2,3-b]pyridinyl acrylamides and epoxides thereof |
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