JP5511385B2 - 細胞骨格活性rhoキナーゼインヒビター化合物、組成物及び使用 - Google Patents
細胞骨格活性rhoキナーゼインヒビター化合物、組成物及び使用 Download PDFInfo
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- JP5511385B2 JP5511385B2 JP2009541644A JP2009541644A JP5511385B2 JP 5511385 B2 JP5511385 B2 JP 5511385B2 JP 2009541644 A JP2009541644 A JP 2009541644A JP 2009541644 A JP2009541644 A JP 2009541644A JP 5511385 B2 JP5511385 B2 JP 5511385B2
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- compound
- heterocycle
- alkyl
- alkenyl
- alkynyl
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Classifications
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- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
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- C—CHEMISTRY; METALLURGY
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| US11/958,214 | 2007-12-17 | ||
| PCT/US2007/087973 WO2008077057A2 (en) | 2006-12-18 | 2007-12-18 | Cytoskeletal active rho kinase inhibitor compounds, composition and use |
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Families Citing this family (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007008926A1 (en) | 2005-07-11 | 2007-01-18 | Aerie Pharmaceuticals, Inc. | Isoquinoline compounds |
| CN101282646B (zh) * | 2005-07-12 | 2013-03-27 | Dmi生物科学公司 | 治疗疾病的方法和产品 |
| CA2664335C (en) | 2006-09-20 | 2014-12-02 | Boehringer Ingelheim International Gmbh | Rho kinase inhibitors |
| US20100022517A1 (en) * | 2006-12-18 | 2010-01-28 | Richards Lori A | Ophthalmic formulation of rho kinase inhibitor compound |
| US8455513B2 (en) | 2007-01-10 | 2013-06-04 | Aerie Pharmaceuticals, Inc. | 6-aminoisoquinoline compounds |
| GB2455176A (en) | 2007-11-01 | 2009-06-03 | Acucela Inc | Amine derivatives useful for treating ophthalmic diseases and disorders |
| US8455514B2 (en) | 2008-01-17 | 2013-06-04 | Aerie Pharmaceuticals, Inc. | 6-and 7-amino isoquinoline compounds and methods for making and using the same |
| MX2010013952A (es) * | 2008-06-18 | 2011-02-18 | Inspire Pharmaceuticals Inc | Proceso para la preparacion de compuestos inhibidores de rho-quinasa. |
| US8410147B2 (en) * | 2008-06-26 | 2013-04-02 | Inspire Pharmaceuticals, Inc. | Method for treating diseases associated with alterations in cellular integrity using Rho kinase inhibitor compounds |
| US20090325960A1 (en) * | 2008-06-26 | 2009-12-31 | Fulcher Emilee H | Method for treating inflammatory diseases using rho kinase inhibitor compounds |
| US8299096B2 (en) * | 2008-06-26 | 2012-10-30 | Inspire Pharmaceuticals, Inc. | Method for treating pulmonary diseases using rho kinase inhibitor compounds |
| US8207195B2 (en) * | 2008-06-26 | 2012-06-26 | Inspire Pharmaceuticals, Inc. | Method for treating neurological and neuropathic diseases using rho kinase inhibitor compounds |
| US20090325959A1 (en) * | 2008-06-26 | 2009-12-31 | Vittitow Jason L | Method for treating ophthalmic diseases using rho kinase inhibitor compounds |
| US20100008968A1 (en) * | 2008-06-26 | 2010-01-14 | Lampe John W | Method for treating cardiovascular diseases using rho kinase inhibitor compounds |
| US8450344B2 (en) | 2008-07-25 | 2013-05-28 | Aerie Pharmaceuticals, Inc. | Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds |
| EP2400969A4 (en) * | 2008-12-04 | 2012-05-16 | Inspire Pharmaceuticals Inc | METHOD FOR TREATING PULMONARY DISEASES USING RHO KINASE INHIBITORY COMPOUNDS |
| ES2553827T3 (es) | 2009-05-01 | 2015-12-14 | Aerie Pharmaceuticals, Inc. | Inhibidores de mecanismo doble para el tratamiento de enfermedad |
| BRPI1010086A2 (pt) * | 2009-06-22 | 2018-02-06 | Dmi Acquisition Corp | método e produtos para tratamento de doenças |
| ES2554688T3 (es) * | 2009-06-22 | 2015-12-22 | Ampio Pharmaceuticals, Inc. | Procedimiento de tratamiento de enfermedades |
| AU2015203100B2 (en) * | 2009-06-22 | 2017-03-16 | Ampio Pharmaceuticals, Inc. | Method for treatment of diseases |
| EP2512239A4 (en) * | 2009-12-14 | 2014-11-26 | Inspire Pharmaceuticals Inc | BROKEN BICYCLIC RHO-KINASE INHIBITOR COMPOUNDS, COMPOSITION AND USE |
| MX2013000664A (es) * | 2010-07-19 | 2013-03-07 | Inspire Pharmaceuticals Inc | Compuestos bifuncionales inhibidores de quinasa de rho, composicion y usos. |
| CA2803689A1 (en) * | 2010-07-27 | 2012-02-02 | Inspire Pharmaceuticals, Inc. | Method for treating ophthalmic diseases using kinase inhibitor compounds in prodrug forms |
| GB201107223D0 (en) * | 2011-04-29 | 2011-06-15 | Amakem Nv | Novel rock inhibitors |
| EP2788472B1 (en) | 2011-12-06 | 2019-02-20 | Astellas Institute for Regenerative Medicine | Method of directed differentiation producing corneal endothelial cells |
| JP5977837B2 (ja) | 2011-12-21 | 2016-08-24 | ノヴィラ・セラピューティクス・インコーポレイテッド | B型肝炎抗ウイルス剤 |
| US20130168825A1 (en) * | 2011-12-30 | 2013-07-04 | Alliance For Sustainable Energy, Llc | Fabrication of ionic liquid electrodeposited cu-sn-zn-s-se thin films and method of making |
| MX373711B (es) | 2012-08-28 | 2020-05-08 | Janssen Sciences Ireland Uc | Sulfamoilarilamidas y su uso como medicamentos para el tratamiento de la hepatitis b. |
| WO2014068035A1 (en) | 2012-10-31 | 2014-05-08 | Amakem Nv | Novel rock inhibitors |
| WO2014100352A1 (en) | 2012-12-19 | 2014-06-26 | Ampio Pharmaceuticals, Inc. | Method for treatment of diseases |
| DK2961732T3 (en) | 2013-02-28 | 2017-07-10 | Janssen Sciences Ireland Uc | SULFAMOYLARYLAMIDS AND USE THEREOF AS MEDICINES TO TREAT HEPATITIS B |
| HUE061618T2 (hu) | 2013-03-15 | 2023-07-28 | Aerie Pharmaceuticals Inc | Vegyület szemrendellenességek kezelésére |
| CN105102451B (zh) | 2013-04-03 | 2018-09-18 | 爱尔兰詹森科学公司 | N-苯基-氨甲酰衍生物及其作为药物用于治疗乙型肝炎的用途 |
| JO3603B1 (ar) | 2013-05-17 | 2020-07-05 | Janssen Sciences Ireland Uc | مشتقات سلفامويل بيرولاميد واستخدامها كادوية لمعالجة التهاب الكبد نوع بي |
| DK2997019T3 (en) | 2013-05-17 | 2018-12-03 | Janssen Sciences Ireland Uc | SULFAMOYLTHIOPHENAMIDE DERIVATIVES AND USE THEREOF AS MEDICINES FOR TREATING HEPATITIS B |
| KR102244937B1 (ko) | 2013-07-25 | 2021-04-27 | 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 | 글리옥사미드 치환된 피롤아미드 유도체 및 b형 간염 치료용 의약으로서의 이의 용도 |
| DK3060547T3 (en) | 2013-10-23 | 2018-01-15 | Janssen Sciences Ireland Uc | CARBOXAMIDE DERIVATIVES AND USE THEREOF AS MEDICINES FOR TREATMENT OF HEPATITS B |
| US10392349B2 (en) | 2014-01-16 | 2019-08-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| US9169212B2 (en) | 2014-01-16 | 2015-10-27 | Novira Therapeutics, Inc. | Azepane derivatives and methods of treating hepatitis B infections |
| EP3102225B1 (en) | 2014-02-05 | 2020-03-25 | Novira Therapeutics Inc. | Combination therapy for treatment of hbv infections |
| US11078193B2 (en) | 2014-02-06 | 2021-08-03 | Janssen Sciences Ireland Uc | Sulphamoylpyrrolamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
| WO2016057306A1 (en) | 2014-10-06 | 2016-04-14 | University Of Houston | Rho associated kinase (rock) inhibitors and their use in treating disease |
| US9884831B2 (en) | 2015-03-19 | 2018-02-06 | Novira Therapeutics, Inc. | Azocane and azonane derivatives and methods of treating hepatitis B infections |
| EP3294871A1 (en) | 2015-05-12 | 2018-03-21 | Platod | Combination of pharmacological and microfluidic features for improved platelets production |
| US10875876B2 (en) | 2015-07-02 | 2020-12-29 | Janssen Sciences Ireland Uc | Cyclized sulfamoylarylamide derivatives and the use thereof as medicaments for the treatment of hepatitis B |
| TW201718496A (zh) | 2015-09-29 | 2017-06-01 | 諾維拉治療公司 | B型肝炎抗病毒劑之晶型 |
| KR102579582B1 (ko) | 2015-11-17 | 2023-09-15 | 에어리 파마슈티컬즈, 인코포레이티드 | 키나아제 억제제 및 이의 중간체의 제조 방법 |
| US9643927B1 (en) | 2015-11-17 | 2017-05-09 | Aerie Pharmaceuticals, Inc. | Process for the preparation of kinase inhibitors and intermediates thereof |
| CN109640980A (zh) | 2016-04-15 | 2019-04-16 | 诺维拉治疗公司 | 包含壳体装配抑制剂的组合和方法 |
| WO2018045091A1 (en) | 2016-08-31 | 2018-03-08 | Aerie Pharmaceuticals, Inc. | Ophthalmic compositions |
| JP2020509004A (ja) * | 2017-02-27 | 2020-03-26 | ヤンセン ファーマシューティカ エヌ.ベー. | Oga阻害剤としての、ピペリジン、モルホリンまたはピペラジンで置換されている[1,2,4]−トリアゾロ[1,5−a]−ピリミジニル誘導体 |
| JP2020515583A (ja) | 2017-03-31 | 2020-05-28 | アエリエ ファーマシューティカルズ インコーポレイテッド | アリールシクロプロピル−アミノ−イソキノリニルアミド化合物 |
| SG11202002947TA (en) * | 2017-11-03 | 2020-04-29 | Aclaris Therapeutics Inc | Substituted pyrrolopyrimidine jak inhibitors and methods of making and using the same |
| JP2021515769A (ja) | 2018-03-14 | 2021-06-24 | ヤンセン・サイエンシズ・アイルランド・アンリミテッド・カンパニー | カプシド集合調節剤の投薬レジメン |
| CN108929258A (zh) * | 2018-07-09 | 2018-12-04 | 张立国 | 一种Rho激酶抑制剂及其在癌症治疗中的应用 |
| CN108569990A (zh) * | 2018-07-09 | 2018-09-25 | 张立国 | 多取代吡咯烷衍生物及其作为Rho激酶抑制剂在癌症中的应用 |
| BR112021002479A2 (pt) | 2018-08-10 | 2021-07-27 | Aclaris Therapeutics, Inc. | composto, composição farmacêutica, método para inibir a atividade de itk ou jak3 em uma população de células, método para tratar um distúrbio mediado por itk ou jak3 em um indivíduo necessitando do mesmo e uso de um composto |
| WO2020047229A1 (en) | 2018-08-29 | 2020-03-05 | University Of Massachusetts | Inhibition of protein kinases to treat friedreich ataxia |
| AU2019337703B2 (en) | 2018-09-14 | 2023-02-02 | Aerie Pharmaceuticals, Inc. | Aryl cyclopropyl-amino-isoquinolinyl amide compounds |
| WO2020072456A1 (en) * | 2018-10-02 | 2020-04-09 | Case Western Reserve University | Compounds for treating myelin related disorders |
| MA55020A (fr) | 2019-02-22 | 2021-12-29 | Janssen Sciences Ireland Unlimited Co | Dérivés d'amide utiles dans le traitement d'une infection par le virus de l'hépatite b ou de maladies induites par le virus de l'hépatite b |
| AR119732A1 (es) | 2019-05-06 | 2022-01-05 | Janssen Sciences Ireland Unlimited Co | Derivados de amida útiles en el tratamiento de la infección por vhb o de enfermedades inducidas por vhb |
| CN110215519A (zh) * | 2019-07-12 | 2019-09-10 | 温州医科大学附属眼视光医院 | 药物修饰型人工晶状体及其制备方法和应用 |
| CN114133394B (zh) * | 2020-08-12 | 2023-12-08 | 赛诺哈勃药业(成都)有限公司 | 一种选择性针对细胞周期依赖性激酶12活性的化合物、制备方法及医药用途 |
| MX2024002139A (es) | 2021-08-18 | 2024-03-06 | Chemocentryx Inc | Arilsulfonil(hidroxi)piperidinas como inhibidores de ccr6. |
| WO2023023534A2 (en) | 2021-08-18 | 2023-02-23 | Chemocentryx, Inc. | Aryl sulfonyl compounds as ccr6 inhibitors |
| US12084453B2 (en) | 2021-12-10 | 2024-09-10 | Incyte Corporation | Bicyclic amines as CDK12 inhibitors |
| CN116891460A (zh) * | 2023-07-12 | 2023-10-17 | 浙江大学 | 一种吲唑类衍生物或其药用盐及应用 |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4524816A (en) * | 1984-02-21 | 1985-06-25 | Dentsply Research & Development Corp. | Centrifugal casting furnace |
| US6339099B1 (en) | 1997-06-20 | 2002-01-15 | Dupont Pharmaceuticals Company | Guanidine mimics as factor Xa inhibitors |
| YU54202A (sh) | 2000-01-18 | 2006-01-16 | Agouron Pharmaceuticals Inc. | Jedinjenja indazola, farmaceutske smeše i postupci za stimulisanje i inhibiranje ćelijske proliferacije |
| US7217722B2 (en) | 2000-02-01 | 2007-05-15 | Kirin Beer Kabushiki Kaisha | Nitrogen-containing compounds having kinase inhibitory activity and drugs containing the same |
| US7105682B2 (en) * | 2001-01-12 | 2006-09-12 | Amgen Inc. | Substituted amine derivatives and methods of use |
| EP1378247B1 (en) | 2001-04-11 | 2016-08-24 | Senju Pharmaceutical Co., Ltd. | Visual function disorder improving agents |
| ATE449763T1 (de) | 2001-04-16 | 2009-12-15 | Eisai R&D Man Co Ltd | 1h-indazolverbindungen die jnk hemmen |
| JPWO2002100833A1 (ja) | 2001-06-12 | 2004-09-24 | 住友製薬株式会社 | Rhoキナーゼ阻害剤 |
| US6867221B2 (en) | 2001-08-30 | 2005-03-15 | Kowa Co., Ltd. | Cyclic amine compounds and pharmaceutical composition containing the same |
| TW200300350A (en) * | 2001-11-14 | 2003-06-01 | Bristol Myers Squibb Co | C-5 modified indazolylpyrrolotriazines |
| US20030187026A1 (en) | 2001-12-13 | 2003-10-02 | Qun Li | Kinase inhibitors |
| AU2003257588A1 (en) | 2002-08-29 | 2004-03-19 | Santen Pharmaceutical Co., Ltd. | REMEDY FOR GLAUCOMA COMPRISING Rho KINASE INHIBITOR AND PROSTAGLANDINS |
| JPWO2004024717A1 (ja) | 2002-09-12 | 2006-01-05 | 麒麟麦酒株式会社 | キナーゼ阻害活性を有するイソキノリン誘導体およびそれを含む医薬 |
| ATE536353T1 (de) | 2003-08-20 | 2011-12-15 | Vertex Pharma | 2-(4-amino-1,2,5-oxadiazol-4-yl)-imidazol- verbindungen als protein kinase inhibitoren |
| WO2006135383A2 (en) | 2004-08-04 | 2006-12-21 | Myriad Genetics, Inc. | Indazoles |
| US20070054916A1 (en) | 2004-10-01 | 2007-03-08 | Amgen Inc. | Aryl nitrogen-containing bicyclic compounds and methods of use |
| WO2006051311A1 (en) * | 2004-11-12 | 2006-05-18 | Galapagos Nv | Nitrogen heteroaromatic compounds which bind to the active site of protein kinase enzymes |
| AR054416A1 (es) | 2004-12-22 | 2007-06-27 | Incyte Corp | Pirrolo [2,3-b]piridin-4-il-aminas y pirrolo [2,3-b]pirimidin-4-il-aminas como inhibidores de las quinasas janus. composiciones farmaceuticas. |
| ES2380795T3 (es) * | 2005-05-20 | 2012-05-18 | Vertex Pharmaceuticals, Inc. | Pirrolopiridinas útiles como inhibidores de proteínas quinasas |
| CA2615291A1 (en) * | 2005-07-14 | 2007-01-18 | Astellas Pharma Inc. | Heterocyclic janus kinase 3 inhibitors |
| US7618985B2 (en) | 2005-12-08 | 2009-11-17 | N.V. Organon | Isoquinoline derivatives |
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- 2007-12-18 RU RU2009127798/04A patent/RU2470928C2/ru not_active IP Right Cessation
- 2007-12-18 WO PCT/US2007/087973 patent/WO2008077057A2/en not_active Ceased
- 2007-12-18 CN CN2012105761391A patent/CN103254172A/zh active Pending
- 2007-12-18 EP EP07869450A patent/EP2099457A4/en not_active Withdrawn
- 2007-12-18 CA CA002672825A patent/CA2672825A1/en not_active Abandoned
- 2007-12-18 KR KR1020097012595A patent/KR20090091767A/ko not_active Ceased
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2011
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2012
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Also Published As
| Publication number | Publication date |
|---|---|
| RU2009127798A (ru) | 2011-01-27 |
| CN101583361B (zh) | 2013-01-23 |
| US8604218B2 (en) | 2013-12-10 |
| WO2008077057A2 (en) | 2008-06-26 |
| WO2008077057A3 (en) | 2008-08-21 |
| EP2099457A2 (en) | 2009-09-16 |
| US20130012543A1 (en) | 2013-01-10 |
| US8604205B2 (en) | 2013-12-10 |
| JP2010513319A (ja) | 2010-04-30 |
| BRPI0720457A2 (pt) | 2014-01-14 |
| AU2007333715A1 (en) | 2008-06-26 |
| RU2470928C2 (ru) | 2012-12-27 |
| CA2672825A1 (en) | 2008-06-26 |
| CN103254172A (zh) | 2013-08-21 |
| KR20090091767A (ko) | 2009-08-28 |
| US20120046275A1 (en) | 2012-02-23 |
| CN101583361A (zh) | 2009-11-18 |
| MX2009006493A (es) | 2009-09-10 |
| EP2099457A4 (en) | 2011-08-17 |
| US8071779B2 (en) | 2011-12-06 |
| AU2007333715B2 (en) | 2013-01-10 |
| US20080214614A1 (en) | 2008-09-04 |
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