CN105492444B - 作为rock抑制剂的三环吡啶-甲酰胺衍生物 - Google Patents

作为rock抑制剂的三环吡啶-甲酰胺衍生物 Download PDF

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CN105492444B
CN105492444B CN201480047827.6A CN201480047827A CN105492444B CN 105492444 B CN105492444 B CN 105492444B CN 201480047827 A CN201480047827 A CN 201480047827A CN 105492444 B CN105492444 B CN 105492444B
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formamides
pyridine
independently selected
methyl
chromenes
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CN105492444A (zh
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陈丽芬
胡子伦
王彩兰
S·帕蒂尔
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Bristol Myers Squibb Co
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    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
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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
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
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CN201480047827.6A 2013-07-02 2014-07-01 作为rock抑制剂的三环吡啶-甲酰胺衍生物 Expired - Fee Related CN105492444B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361842098P 2013-07-02 2013-07-02
US61/842,098 2013-07-02
PCT/US2014/044988 WO2015002915A1 (en) 2013-07-02 2014-07-01 Tricyclic pyri do-carboxam i d e derivatives as rock inhibitors

Publications (2)

Publication Number Publication Date
CN105492444A CN105492444A (zh) 2016-04-13
CN105492444B true CN105492444B (zh) 2018-09-07

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US (1) US9914740B2 (https=)
EP (1) EP3016951B1 (https=)
JP (1) JP6434968B2 (https=)
CN (1) CN105492444B (https=)
AR (1) AR096788A1 (https=)
ES (1) ES2633987T3 (https=)
TW (1) TW201506024A (https=)
WO (1) WO2015002915A1 (https=)

Families Citing this family (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2016509066A (ja) 2013-02-22 2016-03-24 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ アダプター関連キナーゼ１（ａａｋ１）の阻害剤としての５ｈ−クロメノ［３，４−ｃ］ピリジン
CN105102448B (zh) 2013-02-28 2018-03-06 百时美施贵宝公司 作为rock1和rock2抑制剂的苯基吡唑衍生物
AR094929A1 (es) 2013-02-28 2015-09-09 Bristol Myers Squibb Co Derivados de fenilpirazol como inhibidores potentes de rock1 y rock2
WO2015002926A1 (en) 2013-07-02 2015-01-08 Bristol-Myers Squibb Company Tricyclic pyrido-carboxamide derivatives as rock inhibitors
AR096788A1 (es) 2013-07-02 2016-02-03 Bristol Myers Squibb Co Compuestos tricíclicos de carboxamida como inhibidores potentes de rock
EP3054955B1 (en) 2013-10-11 2018-05-30 Bristol-Myers Squibb Company Pyrrolotriazine kinase inhibitors
US9902702B2 (en) 2014-07-15 2018-02-27 Bristol-Myers Squibb Company Spirocycloheptanes as inhibitors of rock
AR103990A1 (es) 2015-01-09 2017-06-21 Bristol Myers Squibb Co Ureas cíclicas como inhibidoras de rock
TW201706265A (zh) 2015-03-09 2017-02-16 必治妥美雅史谷比公司 做為Ｒｈｏ激酶（ＲＯＣＫ）抑制劑之內醯胺
ES2740224T3 (es) 2015-04-10 2020-02-05 Bristol Myers Squibb Co 6H-isocromeno[3,4-c]piridinas y benzo[c][1,7]naftiridin-6-(5H)-onas como inhibidores de la cinasa asociada a adaptador 1 (AAK1)
CN107709314A (zh) 2015-06-11 2018-02-16 巴斯利尔药物国际股份公司 外排泵抑制剂及其治疗性用途
ES2862727T3 (es) * 2015-08-26 2021-10-07 Fundacion Del Sector Publico Estatal Centro Nac De Investigaciones Oncologicas Carlos Iii F S P Cnio Compuestos tricíclicos condensados como inhibidores de proteínas quinasas
AR107354A1 (es) 2016-01-13 2018-04-18 Bristol Myers Squibb Co Salicilamidas espiroheptanos y compuestos relacionados como inhibidores de rock
EP3426674A4 (en) 2016-03-09 2019-08-14 Blade Therapeutics, Inc. CYCLIC KETO AMID COMPOUNDS AS CALPAIN MODULATORS AND METHOD FOR THE PRODUCTION AND USE THEREOF
ES2781309T3 (es) 2016-05-27 2020-09-01 Bristol Myers Squibb Co Triazolonas y tetrazolonas como inhibidores de ROCK
AU2017292646A1 (en) 2016-07-05 2019-02-07 Blade Therapeutics, Inc. Calpain modulators and therapeutic uses thereof
EP3481816B1 (en) 2016-07-07 2020-06-24 Bristol-Myers Squibb Company Lactam, cyclic urea and carbamate, and triazolone derivatives as potent and selective rock inhibitors
ES2821877T3 (es) 2016-07-07 2021-04-28 Bristol Myers Squibb Co Espirolactamas como inhibidores de ROCK
JP7155102B2 (ja) 2016-07-07 2022-10-18 ブリストル－マイヤーズ スクイブ カンパニー Ｒｏｃｋ阻害剤としてのスピロ縮合環尿素
WO2018064119A1 (en) 2016-09-28 2018-04-05 Blade Therapeutics, Inc. Calpain modulators and therapeutic uses thereof
WO2018102325A1 (en) * 2016-11-30 2018-06-07 Bristol-Myers Squibb Company Tricyclic rho kinase inhibitors
EP3640242B1 (en) * 2017-06-16 2023-04-19 Hitgen Ltd. Rock-inhibiting compound and uses thereof
EP3652165B1 (en) 2017-07-12 2021-08-25 Bristol-Myers Squibb Company Five membered-aminoheterocyclic and 5,6-or 6,6-membered bicyclic aminoheterocyclic inhibitors of rock for the treatment of heart failure
EP3652167B1 (en) 2017-07-12 2021-06-02 Bristol-Myers Squibb Company Spiroheptanyl hydantoins as rock inhibitors
CN110869360B (zh) 2017-07-12 2023-12-15 百时美施贵宝公司 作为rock抑制剂的苯乙酰胺类
US12060341B2 (en) 2017-07-12 2024-08-13 Bristol-Myers Squibb Company Spiroheptanyl hydantoins as ROCK inhibitors
TW201908293A (zh) 2017-07-12 2019-03-01 美商必治妥美雅史谷比公司 作為rock抑制劑之5員及雙環雜環醯胺
WO2019089868A1 (en) 2017-11-03 2019-05-09 Bristol-Myers Squibb Company Diazaspiro rock inhibitors
JP2021523092A (ja) * 2018-03-21 2021-09-02 ピラマル・ファーマ・リミテッドＰｉｒａｍａｌ Ｐｈａｒｍａ Ｌｉｍｉｔｅｄ アルファ−（ジアリールメチル）アルキルアミンの改良された不斉合成
CN108299429B (zh) * 2018-04-09 2021-10-08 中南大学 一类八氢苯并萘啶化合物及其制备方法和应用
CN110283119A (zh) * 2018-04-20 2019-09-27 长沙理工大学 一种合成全碳基取代吡啶衍生物的方法
CN110759923B (zh) * 2018-07-26 2022-08-30 上海医药工业研究院有限公司 嘧啶并吡咯并哒嗪衍生物、其中间体、制备方法、药物组合物和用途
WO2021174167A1 (en) * 2020-02-28 2021-09-02 Remix Therapeutics Inc. Compounds and methods for modulating splicing
CN115697968B (zh) * 2020-05-28 2024-03-29 杭州中美华东制药有限公司 (s)-2-氨基-3-(4-(2,3-二甲基吡啶-4-基)苯基丙酸甲酯及其盐的制备方法
CN112010853A (zh) * 2020-09-01 2020-12-01 成都大学 一种食品中杂环胺风险物质norharman及类似物的合成方法
AU2021356130A1 (en) 2020-10-08 2023-05-18 Redona Therapeutics, Inc. Benzo[h]quinazolin-4-amine and thieno[3,2-h]quinazolin-4-amine derivatives for the treatment of cancer
US20240400584A1 (en) * 2021-08-30 2024-12-05 Remix Therapeutics Inc. Compounds and methods for modulating splicing
JPWO2023085369A1 (https=) 2021-11-11 2023-05-19
CN114544851B (zh) * 2022-02-22 2023-12-15 苏州正济医药研究有限公司 一种测定邻氯苯甘氨酸甲酯酒石酸盐及杂质的分析方法
CN117105779A (zh) * 2023-07-18 2023-11-24 河南师范大学 一种5-溴-2-甲酰基苯甲酸甲酯的制备方法
CN117263934A (zh) * 2023-08-16 2023-12-22 上海凌凯医药科技有限公司 一种5H-苯并[c][1,6]萘啶-6-酮类衍生物的制备方法
CN119874716B (zh) * 2025-03-27 2025-07-15 上海隆盛化工有限公司 1-氯-6,8-二氟-7-异丙基苯并呋喃并[2,3-c]吡啶及其合成方法和应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001068648A1 (en) * 2000-03-15 2001-09-20 Aventis Pharma Deutschland Gmbh Substituted beta-carbolines with ikb-kinase inhibiting activity

Family Cites Families (101)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HU168036B (https=) 1973-11-09 1976-02-28
HU168776B (https=) 1973-11-09 1976-07-28
CA1098910A (en) 1978-06-15 1981-04-07 Robert N. Schut 3-amino-2-(5-fluoro and 5-methoxy-1h-indol-3-yl) propanoic acid derivatives
JPS57116067A (en) 1981-01-12 1982-07-19 Sankyo Kagaku Kk Novel 8-quinolinesulfonyl derivative, its synthesis and use
DE3703435A1 (de) 1987-02-05 1988-08-18 Thomae Gmbh Dr K Neue thiazole, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
IE68593B1 (en) 1989-12-06 1996-06-26 Sanofi Sa Heterocyclic substituted acylaminothiazoles their preparation and pharmaceutical compositions containing them
EP0828738B1 (de) 1995-05-26 2003-12-17 Bayer CropScience AG Pyridyl-thiazole und deren verwendung zum schutz von pflanzen gegen befall durch mikroorganismen
US6187797B1 (en) 1996-12-23 2001-02-13 Dupont Pharmaceuticals Company Phenyl-isoxazoles as factor XA Inhibitors
DE69720773T2 (de) 1996-12-23 2004-01-29 Bristol Myers Squibb Pharma Co SAUERSTOFF ODER SCHWEFEL ENTHALTENDE 5-GLIEDRIGE HETEROAROMATISHE DERIVATIVE ALS FACTOR Xa HEMMER
US6436966B1 (en) 1997-10-27 2002-08-20 Takeda Chemical Ind., Ltd. Adenosine A3 receptor antagonists
AU3702699A (en) 1998-04-08 1999-11-01 Bayer Aktiengesellschaft Substituted oxazolyle and thiazolyl uracil herbicides
CN1376150A (zh) 1999-07-26 2002-10-23 盐野义制药株式会社 具有血栓形成素受体拮抗作用的药物组合物
HK1054039B (zh) * 2000-03-15 2010-04-16 萨诺费－阿文蒂斯德国有限公司 取代的β-咔啉
GB0010183D0 (en) 2000-04-26 2000-06-14 Ferring Bv Inhibitors of dipeptidyl peptidase IV
EP1310494B1 (en) 2000-08-11 2012-01-25 Nippon Chemiphar Co., Ltd. PPAR (delta) ACTIVATORS
JP2002053566A (ja) 2000-08-11 2002-02-19 Japan Tobacco Inc チアゾール化合物及びその医薬用途
US20020173507A1 (en) 2000-08-15 2002-11-21 Vincent Santora Urea compounds and methods of uses
US20020103192A1 (en) 2000-10-26 2002-08-01 Curtin Michael L. Inhibitors of histone deacetylase
WO2002051442A1 (en) 2000-12-26 2002-07-04 Takeda Chemical Industries, Ltd. Concomitant drugs
JPWO2002062775A1 (ja) 2001-02-02 2004-06-10 山之内製薬株式会社 ２−アシルアミノチアゾール誘導体又はその塩
MY130778A (en) 2001-02-09 2007-07-31 Vertex Pharma Heterocyclic inhibitiors of erk2 and uses thereof
US20020177594A1 (en) 2001-03-14 2002-11-28 Curtin Michael L. Inhibitors of histone deacetylase
US7078422B2 (en) 2001-03-23 2006-07-18 Nippon Chemiphar Co., Ltd. Activator for peroxisome proliferator-activated receptor
US20050009843A1 (en) 2001-04-26 2005-01-13 Kiyoshi Nakayama Medicine for inhibiting drug elimination pump
EP1402900A1 (en) 2001-06-11 2004-03-31 Takeda Chemical Industries, Ltd. Medicinal compositions
GB0123589D0 (en) 2001-10-01 2001-11-21 Syngenta Participations Ag Organic compounds
AU2002349705A1 (en) 2001-12-03 2003-06-17 Japan Tobacco Inc. Azole compound and medicinal use thereof
JP4120586B2 (ja) 2002-01-18 2008-07-16 アステラス製薬株式会社 ２−アシルアミノチアゾール誘導体又はその塩
EP1467981A1 (en) 2002-01-25 2004-10-20 Kylix Pharmaceuticals B.V. 4(hetero-) aryl substituted (thia-/oxa-/pyra) zoles for inhibition of tie-2
US7229987B2 (en) 2002-05-13 2007-06-12 Eli Lilly And Company Multicyclic compounds for use as melanin concentrating hormone antagonists in the treatment of obesity and diabetes
EP1534273A4 (en) 2002-07-18 2007-08-22 Bristol Myers Squibb Co MODULATORS OF THE GLUCOCORTICOID RECEPTOR AND METHOD
TW200424183A (en) 2002-08-09 2004-11-16 Nps Pharma Inc New compounds
AU2003265395A1 (en) 2002-08-14 2004-03-03 Ppd Discovery, Inc. Prenylation inhibitors and methods of their synthesis and use
AR043057A1 (es) 2002-10-30 2005-07-13 Vertex Pharma Compuestos derivados de piridintiazoles como inhibidores de la quinasa rock y otras proteinas quinasa
GB0230087D0 (en) 2002-12-24 2003-01-29 Astrazeneca Ab Therapeutic agents
GB0302672D0 (en) 2003-02-06 2003-03-12 Astrazeneca Ab Pharmaceutical formulations
WO2004071509A1 (ja) 2003-02-12 2004-08-26 Nippon Chemiphar Co., Ltd. オリゴデンドロサイト分化促進剤
BRPI0409227C1 (pt) 2003-04-07 2021-05-25 Axys Pharm Inc composto, composição farmacêutica, uso de um composto e processo para a preparação de um composto de fórmula (i)
SG169900A1 (en) 2003-04-16 2011-04-29 Memory Pharm Corp 4 - (3,4 - disubstituted phenyl) - pyrrolidin-2-one compounds as phosphodiesterase 4 inhibitors
CN100545161C (zh) 2003-08-15 2009-09-30 中国科学院上海药物研究所 一类杂环衍生物、制备方法及其用途
US7351727B2 (en) 2003-09-02 2008-04-01 Bristol-Myers Squibb Company Inhibitors of 15-lipoxygenase
ZA200602755B (en) 2003-09-06 2007-06-27 Vertex Pharma Modulators of ATP-binding cassette transporters
TWI336697B (en) 2003-09-19 2011-02-01 Solvay Pharm Bv Thiazole derivatives as cannabinoid receptor modulators
WO2005044194A2 (en) 2003-10-28 2005-05-19 Pharmacia Corporation TREATMENT OR PREVENTION OF NEOPLASIA BY USE OF AN Hsp90 INHIBITOR
JP2007509968A (ja) 2003-10-28 2007-04-19 ファルマシア・コーポレーション 新形成を治療または予防するためのｈｓｐ９０阻害剤およびホスホジエステラーゼ阻害剤を含む組み合わせ
US20080275062A1 (en) 2004-01-30 2008-11-06 David Harold Drewry Chemical Compounds
MXPA06008606A (es) 2004-01-30 2007-04-13 Vertex Pharma Moduladores de transportadores con casete de union a atp.
WO2005077345A1 (en) 2004-02-03 2005-08-25 Astrazeneca Ab Compounds for the treatment of gastro-esophageal reflux disease
WO2005077373A2 (en) 2004-02-03 2005-08-25 Astrazeneca Ab Treatment of gastro-esophageal reflux disease (gerd)
MY148488A (en) 2004-02-18 2013-04-30 Astrazeneca Ab Additional heteropolycyclic compounds and their use as metabotropic glutamate receptor antagonists
EP1717225A4 (en) 2004-02-18 2009-10-21 Kyorin Seiyaku Kk BICYCLIC AMID DERIVATIVES
US7259155B2 (en) 2004-05-05 2007-08-21 Otsuka Pharmaceutical Factory, Inc. Phosphonic diester derivatives
TW200637559A (en) 2005-03-29 2006-11-01 Shionogi & Co 3-propenylcefem derivative
FR2885129B1 (fr) 2005-04-29 2007-06-15 Proskelia Sas Nouveaux derives de l'ureee substituee parun thiazole ou benzothiazole, leur procede de preparation, leur application a titre de medicaments, les compositions pharmaceutiques les renfermant et utilisation.
UA92746C2 (en) 2005-05-09 2010-12-10 Акилайон Фармасьютикалз, Инк. Thiazole compounds and methods of use
US7655446B2 (en) 2005-06-28 2010-02-02 Vertex Pharmaceuticals Incorporated Crystal structure of Rho-kinase I kinase domain complexes and binding pockets thereof
US20100168102A9 (en) * 2005-07-11 2010-07-01 Devgen Nv Amide Derivatives as Kinase Inhibitors
CA2630920A1 (en) 2005-11-22 2007-05-31 University Of South Florida Inhibition of cell proliferation
WO2007075896A2 (en) 2005-12-22 2007-07-05 Kemia, Inc. Heterocyclic cytokine inhibitors
US8455658B2 (en) 2006-01-25 2013-06-04 Synta Pharmaceuticals Corp. Thiazole and thiadiazole compounds for inflammation and immune-related uses
WO2007116106A1 (es) 2006-04-12 2007-10-18 Palobiofarma, S.L. Nuevos compuestos como antagonistas de los receptores a1 de adenosina
RU2008148962A (ru) 2006-05-12 2010-06-20 Вертекс Фармасьютикалз Инкорпорейтед (Us) Избирательно действующие ингибиторы rоск протеинкиназы и их применение
CA2657247A1 (en) 2006-07-28 2008-01-31 Boehringer Ingelheim International Gmbh Compounds which modulate the cb2 receptor
US7928123B2 (en) 2006-09-25 2011-04-19 Boehringer Ingelheim International Gmbh Compounds which modulate the CB2 receptor
TW200831081A (en) 2006-12-25 2008-08-01 Kyorin Seiyaku Kk Glucokinase activator
WO2008124000A2 (en) 2007-04-02 2008-10-16 Ligand Pharmaceuticals Incorporated Thiazole derivatives as androgen receptor modulator compounds
GB0706793D0 (en) 2007-04-05 2007-05-16 Evotec Ag Compounds
ES2609912T3 (es) 2007-06-22 2017-04-25 Hydra Biosciences, Inc. Compuestos de 2,6-dioxo, -2,3-dihidro-1h-purina útiles para el tratamiento de trastornos relacionados con la actividad del canal trpa1
CN101903349B (zh) 2007-08-27 2014-01-08 Abbvie德国有限责任两合公司 4-(4-吡啶基)-苯甲酰胺及其作为rock活性调节剂的应用
TW200916447A (en) 2007-08-29 2009-04-16 Methylgene Inc Sirtuin inhibitors
ES2331220B1 (es) 2007-10-02 2010-09-23 Palobiofarma, S.L. Nuevos compuestos como antagonistas de los receptores a1 de adenosina.
WO2009057827A1 (en) 2007-10-31 2009-05-07 Nissan Chemical Industries, Ltd. Pyridazinone derivatives and use thereof as p2x7 receptor inhibitors
CA2704684A1 (en) 2007-11-07 2009-05-14 Boehringer Ingelheim International Gmbh Compounds which modulate the cb2 receptor
WO2009067607A2 (en) 2007-11-20 2009-05-28 Memory Pharmaceuticals Corporation Combinations of pde4 inhibitors and antipsychotics for the treatment of psychotic disorders
WO2009081222A1 (en) 2007-12-21 2009-07-02 Glenmark Pharmaceuticals, S.A. Substituted tricyclic pyridine or pyrimidine vanilloid receptor ligands
WO2009086303A2 (en) 2007-12-21 2009-07-09 University Of Rochester Method for altering the lifespan of eukaryotic organisms
WO2009099195A1 (ja) 2008-02-08 2009-08-13 Shiseido Company Ltd. 美白剤及び皮膚外用剤
WO2009114552A1 (en) 2008-03-10 2009-09-17 The Board Of Trustees Of The Leland Stanford Junior University Heteroaryl compounds, compositions, and methods of use in cancer treatment
US20120108614A1 (en) 2008-05-14 2012-05-03 Chong Jayhong A Compounds and compositions for treating chemical warfare agent-induced injuries
WO2010028193A1 (en) 2008-09-03 2010-03-11 Repligen Corporation Compounds including pimelic acid derivatives as hdac inhibitors
US20100063085A1 (en) * 2008-09-11 2010-03-11 University Court Of The University Of Dundee Method of treating learning impairment in down's syndrome subjects
WO2010029300A1 (en) 2008-09-12 2010-03-18 Biolipox Ab Bis aromatic compounds for use in the treatment of inflammation
US20120046305A1 (en) 2008-09-24 2012-02-23 Moran Magdalene M Methods and compositions for treating respiratory disorders
CA2747354C (en) 2008-12-19 2016-12-06 Novartis Ag Isoxazoline derivatives and their use as pesticide
EP2370407B1 (en) * 2008-12-19 2014-06-18 Bristol-Myers Squibb Company Carbazole and carboline kinase inhibitors
SG172352A1 (en) 2008-12-23 2011-07-28 Abbott Lab Anti-viral compounds
JP2012051804A (ja) * 2008-12-26 2012-03-15 Kyoto Univ Ｅｇ５阻害剤
UA103918C2 (en) 2009-03-02 2013-12-10 Айерем Элелси N-(hetero)aryl, 2-(hetero)aryl-substituted acetamides for use as wnt signaling modulators
US8362249B2 (en) 2009-04-27 2013-01-29 Boehringer Ingelheim International Gmbh CXCR3 receptor antagonists
JP2012529518A (ja) 2009-06-09 2012-11-22 アブラクシス バイオサイエンス リミテッド ライアビリティー カンパニー ヘッジホッグシグナル伝達のピリジル−トリアジン阻害剤
EP3103452A1 (en) 2009-08-25 2016-12-14 Abraxis BioScience, LLC Combination therapy with nanoparticle compositions of taxane and hedgehog inhibitors
JP5856064B2 (ja) 2009-11-17 2016-02-09 ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン 治療特性を有する１，４−ベンゾジアゼピン−２，５−ジオンおよび関連化合物
AU2010330743A1 (en) 2009-12-18 2012-07-05 Activesite Pharmaceuticals, Inc. Prodrugs of inhibitors of plasma kallikrein
US9216995B2 (en) 2010-04-12 2015-12-22 Shionogi & Co., Ltd. Pyridone derivative having integrase inhibitory activity
WO2011130740A2 (en) 2010-04-16 2011-10-20 H. Lee Moffitt Cancer Center And Research Institute, Inc. Pyridylthiazole-based ureas as inhibitors of rho associated protein kinase (rock) and methods of use
WO2011159857A1 (en) * 2010-06-16 2011-12-22 Bristol-Myers Squibb Company Carboline carboxamide compounds useful as kinase inhibitors
WO2012054367A1 (en) * 2010-10-19 2012-04-26 Boehringer Ingelheim International Gmbh Rho kinase inhibitors
US8703953B2 (en) 2012-03-09 2014-04-22 Bristol-Myers Squibb Company Aryl ether-base kinase inhibitors
DK2822555T3 (en) * 2012-03-09 2018-02-05 Lexicon Pharmaceuticals Inc Inhibition of adapter-associated kinase 1 for the treatment of pain
WO2015002926A1 (en) 2013-07-02 2015-01-08 Bristol-Myers Squibb Company Tricyclic pyrido-carboxamide derivatives as rock inhibitors
AR096788A1 (es) 2013-07-02 2016-02-03 Bristol Myers Squibb Co Compuestos tricíclicos de carboxamida como inhibidores potentes de rock

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001068648A1 (en) * 2000-03-15 2001-09-20 Aventis Pharma Deutschland Gmbh Substituted beta-carbolines with ikb-kinase inhibiting activity

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Rho/Rho-kinase and C-reactive protein relationship in hypertension and atherosclerosis;Lorenzo A. Calo`;《Nephrol Dial Transplant》;20061231;第21卷;1131-1132 *

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