JP5235887B2 - Ｒｈｏキナーゼ阻害剤 - Google Patents

Ｒｈｏキナーゼ阻害剤 Download PDF

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Publication number
JP5235887B2
JP5235887B2 JP2009529306A JP2009529306A JP5235887B2 JP 5235887 B2 JP5235887 B2 JP 5235887B2 JP 2009529306 A JP2009529306 A JP 2009529306A JP 2009529306 A JP2009529306 A JP 2009529306A JP 5235887 B2 JP5235887 B2 JP 5235887B2
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Japan
Prior art keywords
oxo
dihydro
isoquinolin
chloro
phenyl
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Expired - Fee Related
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JP2009529306A
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Japanese (ja)
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JP2010504342A5 (cg-RX-API-DMAC7.html
JP2010504342A (ja
Inventor
トッド ボサナック
ジョン ディヴィッド ジン
ユージーン リチャード ヒッキー
トーマス マーティン カーレイン
ウェイミン リウ
アンソニー エス プロコポウィッツ
チェン コン シー
ロジャー ジョン スノウ
マイケル ロバート ターナー
フランク ウー
エリック リチャード ヤング
サビーン ケイ シュリアー
Original Assignee
アエリー ファーマシューティカルズ インコーポレイテッド
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
    • C07D217/24—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/88—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/88—Oxygen atoms
    • C07D239/90—Oxygen atoms with acyclic radicals attached in position 2 or 3
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/08—Bridged systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Ophthalmology & Optometry (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
JP2009529306A 2006-09-20 2007-09-13 Ｒｈｏキナーゼ阻害剤 Expired - Fee Related JP5235887B2 (ja)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US82628406P 2006-09-20 2006-09-20
US60/826,284 2006-09-20
US86448406P 2006-11-06 2006-11-06
US60/864,484 2006-11-06
PCT/US2007/078343 WO2008036540A2 (en) 2006-09-20 2007-09-13 Rho kinase inhibitors

Publications (3)

Publication Number Publication Date
JP2010504342A JP2010504342A (ja) 2010-02-12
JP2010504342A5 JP2010504342A5 (cg-RX-API-DMAC7.html) 2010-08-26
JP5235887B2 true JP5235887B2 (ja) 2013-07-10

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JP2009529306A Expired - Fee Related JP5235887B2 (ja) 2006-09-20 2007-09-13 Ｒｈｏキナーゼ阻害剤

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US (5) US8809326B2 (cg-RX-API-DMAC7.html)
EP (2) EP2526948A1 (cg-RX-API-DMAC7.html)
JP (1) JP5235887B2 (cg-RX-API-DMAC7.html)
AR (1) AR062900A1 (cg-RX-API-DMAC7.html)
CA (1) CA2664335C (cg-RX-API-DMAC7.html)
CL (1) CL2007002686A1 (cg-RX-API-DMAC7.html)
ES (1) ES2729424T3 (cg-RX-API-DMAC7.html)
TW (1) TW200819133A (cg-RX-API-DMAC7.html)
WO (1) WO2008036540A2 (cg-RX-API-DMAC7.html)

Families Citing this family (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007008942A2 (en) * 2005-07-11 2007-01-18 Aerie Pharmaceuticals, Inc. Phenylamino-acetic acid [1-(pyridin-4-yl)-methylidene]-hydrazide derivatives and related compounds as modulators of g protein-coupled receptor kinases for the treatment of eye diseases
US7470787B2 (en) * 2005-07-11 2008-12-30 Aerie Pharmaceuticals, Inc. Isoquinoline compounds
EP2526948A1 (en) 2006-09-20 2012-11-28 Aerie Pharmaceuticals, Inc. RHO kinase inhibitors
US20080200467A1 (en) * 2006-11-02 2008-08-21 Arete Therapeutics, Inc. Soluble epoxide hydrolase inhibitors
US8455513B2 (en) 2007-01-10 2013-06-04 Aerie Pharmaceuticals, Inc. 6-aminoisoquinoline compounds
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
BRPI0914330A2 (pt) * 2008-06-24 2019-09-24 Sanofi Aventis derivados de isoquinolina e isoquinolinona substituídos bl-e policíclicos
US8450344B2 (en) 2008-07-25 2013-05-28 Aerie Pharmaceuticals, Inc. Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds
ES2610882T3 (es) * 2008-08-19 2017-05-03 Janssen Pharmaceutica, N.V. Antagonistas del receptor al mentol frío
ES2834451T3 (es) 2009-05-01 2021-06-17 Aerie Pharmaceuticals Inc Inhibidores de mecanismo doble para el tratamiento de enfermedades
FR2956816B1 (fr) 2010-03-01 2012-05-18 Univ Joseph Fourier Utilisation de quinolones pour la preparation de medicaments, nouvelles quinolones et leur procede de synthese
US8697911B2 (en) 2010-07-07 2014-04-15 Boehringer Ingelheim International Gmbh Rho kinase inhibitors
US9079880B2 (en) 2010-07-07 2015-07-14 Boehringer Ingelheim International Gmbh Rho kinase inhibitors
JP5769326B2 (ja) 2010-10-19 2015-08-26 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Ｒｈｏキナーゼ阻害薬
CN103864684A (zh) * 2012-12-07 2014-06-18 天津科技大学 一种新颖的3,4-二氢-1(2h)异喹啉类衍生物的合成与抗肿瘤药物的应用
WO2014113620A2 (en) 2013-01-18 2014-07-24 Bristol-Myers Squibb Company Phthalazinones and isoquinolinones as rock inhibitors
CN110396085B (zh) 2013-03-15 2024-11-15 爱尔康公司 联合治疗
US9902702B2 (en) 2014-07-15 2018-02-27 Bristol-Myers Squibb Company Spirocycloheptanes as inhibitors of rock
WO2016028971A1 (en) 2014-08-21 2016-02-25 Bristol-Myers Squibb Company Tied-back benzamide derivatives as potent rock inhibitors
CA2958879A1 (en) 2014-08-22 2016-02-25 Auckland Uniservices Limited Channel modulators
WO2017086941A1 (en) 2015-11-17 2017-05-26 Aerie Pharmaceuticals, Inc. Process for the preparation of kinase inhibitors and intermediates thereof
US9643927B1 (en) 2015-11-17 2017-05-09 Aerie Pharmaceuticals, Inc. Process for the preparation of kinase inhibitors and intermediates thereof
TWI730032B (zh) 2016-01-13 2021-06-11 美商必治妥美雅史谷比公司 作為ｒｏｃｋ抑制劑之螺庚烷水楊酸醯胺及相關化合物
KR102449652B1 (ko) 2016-07-07 2022-09-29 브리스톨-마이어스 스큅 컴퍼니 Rock의 억제제로서의 스피로-융합 시클릭 우레아
CN109640966A (zh) 2016-08-31 2019-04-16 爱瑞制药公司 眼用组合物
KR20190135027A (ko) 2017-03-31 2019-12-05 에어리 파마슈티컬즈, 인코포레이티드 아릴 시클로프로필-아미노-이소퀴놀리닐 아미드 화합물
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
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
JP7313331B2 (ja) 2017-07-12 2023-07-24 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ヘプタニルヒダントイン
ES2951212T3 (es) 2017-07-12 2023-10-18 Bristol Myers Squibb Co Fenilacetamidas como inhibidores de ROCK
KR102568375B1 (ko) * 2018-03-29 2023-08-18 김미희 RhoA 억제제 및 이의 용도
EP3843845A4 (en) 2018-08-29 2022-05-11 University Of Massachusetts INHIBITION OF PROTEIN KINASE FOR THE TREATMENT OF FRIEDREICH'S ATAXIA
CA3112391A1 (en) 2018-09-14 2020-03-19 Aerie Pharmaceuticals, Inc. Aryl cyclopropyl-amino-isoquinolinyl amide compounds
EP4244213A4 (en) * 2020-11-10 2024-11-20 Foghorn Therapeutics Inc. COMPOUNDS AND USES THEREOF
CN115572282B (zh) * 2021-07-05 2024-07-09 华东理工大学 含芳杂环结构的吡唑酰胺类化合物及其制备方法和应用
EP4431596A1 (en) 2021-11-11 2024-09-18 The Doshisha Cryopreservation preparation for corneal endothelial cells and method for producing said cryopreservation preparation

Family Cites Families (102)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2623228C3 (de) * 1976-05-24 1981-09-10 Ludwig Merckle Kg Chem. Pharm. Fabrik, 7902 Blaubeuren N-Acyl-substituierte Benzamide, Verfahren zu ihrer Herstellung und Arzneimittel, enthaltend solche Benzamide
JPS5587771A (en) 1978-12-27 1980-07-02 Teikoku Hormone Mfg Co Ltd 1-phenylisoquinoline derivative
US4456757A (en) * 1981-03-20 1984-06-26 Asahi Kasei Kogyo Kabushiki Kaisha Isoquinolinesulfonyl derivatives and process for the preparation thereof
JPS5993054A (ja) * 1982-11-18 1984-05-29 Asahi Chem Ind Co Ltd イソキノリンスルホン酸アミド誘導体
DK8386A (da) 1986-01-15 1987-07-09 Tpo Pharmachim Nye n-substituerede 1-benzyl-2-carbamoyltetrahydroisoquinoliner og fremgangsmaade til fremstilling af samme
US4911928A (en) * 1987-03-13 1990-03-27 Micro-Pak, Inc. Paucilamellar lipid vesicles
JPH01139528A (ja) * 1987-11-24 1989-06-01 Showa Denko Kk 抗潰瘍剤
EP0389995B1 (en) 1989-03-28 1995-05-31 Nisshin Flour Milling Co., Ltd. Isoquinoline derivatives for the treatment of glaucoma or ocular hypertension
KR920008026A (ko) * 1990-10-24 1992-05-27 오노 화아마슈티칼 캄파니 리미팃드 이소퀴놀리논 유도체 또는 이의 무독성 산부가염 또는 이의 수화물, 이의 제조방법 및 이를 포함하는 약제 조성물
EP0630373A1 (en) 1992-03-12 1994-12-28 Smithkline Beecham Plc Indole derivatives as 5ht1c antagonists
DE4332168A1 (de) * 1993-02-22 1995-03-23 Thomae Gmbh Dr K Cyclische Derivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
US6586425B2 (en) 1996-02-21 2003-07-01 Wisconsin Alumni Research Foundation Cytoskeletal active agents for glaucoma therapy
US5798380A (en) 1996-02-21 1998-08-25 Wisconsin Alumni Research Foundation Cytoskeletal active agents for glaucoma therapy
US5891646A (en) 1997-06-05 1999-04-06 Duke University Methods of assaying receptor activity and constructs useful in such methods
US6720175B1 (en) 1998-08-18 2004-04-13 The Johns Hopkins University School Of Medicine Nucleic acid molecule encoding homer 1B protein
US20020065296A1 (en) 1999-01-13 2002-05-30 Bayer Corporation Heteroaryl ureas containing nitrogen hetero-atoms as p38 kinase inhibitors
AU5413600A (en) 1999-06-14 2001-01-02 Eli Lilly And Company Compounds
NZ519070A (en) 1999-11-26 2005-08-26 Shionogi & Co NPY Y5 antagonists
CA2395772C (en) 1999-12-28 2010-09-28 Eisai Co., Ltd. Sulfonamide-containing heterocyclic compounds
YU54202A (sh) 2000-01-18 2006-01-16 Agouron Pharmaceuticals Inc. Jedinjenja indazola, farmaceutske smeše i postupci za stimulisanje i inhibiranje ćelijske proliferacije
HN2001000008A (es) 2000-01-21 2003-12-11 Inc Agouron Pharmaceuticals Compuesto de amida y composiciones farmaceuticas para inhibir proteinquinasas, y su modo de empleo
WO2001056607A1 (en) 2000-02-03 2001-08-09 Eisai Co., Ltd. Integrin expression inhibitors
US6410566B1 (en) 2000-05-16 2002-06-25 Teijin Limited Cyclic amine derivatives and their use as drugs
US6908741B1 (en) 2000-05-30 2005-06-21 Transtech Pharma, Inc. Methods to identify compounds that modulate RAGE
US6323228B1 (en) 2000-09-15 2001-11-27 Abbott Laboratories 3-substituted indole angiogenesis inhibitors
ATE464292T1 (de) 2000-10-17 2010-04-15 Merck Serono Sa Pharmazeutisch aktive sulfonamid-derivate
US7163800B2 (en) 2000-11-03 2007-01-16 Molecular Devices Corporation Methods of screening compositions for G protein-coupled receptor desensitization inhibitory activity
JP2004523565A (ja) 2001-03-05 2004-08-05 トランス　テック　ファーマ，インコーポレイテッド 治療因子としてのベンゾイミダゾール誘導体
ES2283543T3 (es) 2001-04-20 2007-11-01 Bayer Pharmaceuticals Corporation Inhibicion de raf kinasa usando quinolil-, isoquinolil- o piridil ureas.
US6956035B2 (en) 2001-08-31 2005-10-18 Inotek Pharmaceuticals Corporation Isoquinoline derivatives and methods of use thereof
JP4505228B2 (ja) 2002-01-10 2010-07-21 バイエル・シェーリング・ファルマ・アクチェンゲゼルシャフト Ｒｈｏ−キナーゼ阻害剤
TW200306819A (en) 2002-01-25 2003-12-01 Vertex Pharma Indazole compounds useful as protein kinase inhibitors
US20040180889A1 (en) 2002-03-01 2004-09-16 Pintex Pharmaceuticals, Inc. Pin1-modulating compounds and methods of use thereof
ATE529110T1 (de) 2002-03-05 2011-11-15 Transtech Pharma Inc Mono- und bicyclische azolderivate die die interaktion von liganden mit rage hemmen
GB0206876D0 (en) 2002-03-22 2002-05-01 Merck Sharp & Dohme Therapeutic agents
US7645878B2 (en) * 2002-03-22 2010-01-12 Bayer Healthcare Llc Process for preparing quinazoline Rho-kinase inhibitors and intermediates thereof
CA2483692A1 (en) 2002-05-13 2003-11-27 Norak Biosciences, Inc. Constitutively translocating cell line
EP1541151B1 (en) 2002-08-29 2012-02-22 Santen Pharmaceutical Co., Ltd. REMEDY FOR GLAUCOMA COMPRISING Rho KINASE INHIBITOR AND PROSTAGLANDINS
JPWO2004022753A1 (ja) 2002-08-30 2005-12-22 アンジェスＭｇ株式会社 アクチン関連新規細胞骨格タンパク質ｌａｃｓ
WO2004024717A1 (ja) 2002-09-12 2004-03-25 Kirin Beer Kabushiki Kaisha 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
US7557129B2 (en) 2003-02-28 2009-07-07 Bayer Healthcare Llc Cyanopyridine derivatives useful in the treatment of cancer and other disorders
KR20060027338A (ko) 2003-06-12 2006-03-27 아스텔라스세이야쿠 가부시키가이샤 벤즈 아미드 유도체 또는 그 염
US8362017B2 (en) 2003-08-29 2013-01-29 Exelixis, Inc. C-kit modulators and methods of use
EP1689393A4 (en) 2003-10-06 2008-12-17 Glaxo Group Ltd PREPARATION OF 1,7-DISUBSTITUTED AZABENZIMIDAZOLES AS KINASE INHIBITORS
JP2007008816A (ja) * 2003-10-15 2007-01-18 Ube Ind Ltd 新規イソキノリン誘導体
CN1863779B (zh) 2003-10-15 2010-05-05 宇部兴产株式会社 吲唑衍生物
DE10348023A1 (de) 2003-10-15 2005-05-19 Imtm Gmbh Neue Alanyl-Aminopeptidasen-Inhibitoren zur funktionellen Beeinflussung unterschiedlicher Zellen und zur Behandlung immunologischer, entzündlicher, neuronaler und anderer Erkrankungen
SE0400284D0 (sv) 2004-02-10 2004-02-10 Astrazeneca Ab Novel compounds
JP2005227441A (ja) 2004-02-12 2005-08-25 Konica Minolta Medical & Graphic Inc 光熱写真画像形成材料
US7592357B2 (en) 2004-02-20 2009-09-22 Smithkline Beecham Corporation Compounds
US20080096238A1 (en) 2004-03-30 2008-04-24 Alcon, Inc. High throughput assay for human rho kinase activity with enhanced signal-to-noise ratio
DE102004017438A1 (de) 2004-04-08 2005-11-03 Bayer Healthcare Ag Hetaryloxy-substituierte Phenylaminopyrimidine
US7453002B2 (en) 2004-06-15 2008-11-18 Bristol-Myers Squibb Company Five-membered heterocycles useful as serine protease inhibitors
JP2008503492A (ja) 2004-06-17 2008-02-07 スミスクライン・ビーチャム・コーポレイション Ｒｈｏ−キナーゼの新規阻害剤
JP4478157B2 (ja) 2004-10-13 2010-06-09 エーザイ・アール・アンド・ディー・マネジメント株式会社 ヒドラジド誘導体
UY29198A1 (es) * 2004-11-09 2006-05-31 Cancer Rec Tech Ltd Derivados sustituidos de quinazolinona y derivados sustituidos de quinazolina-2, 4-diona, composiciones conteniéndolos, procedimientos de preparación y aplicaciones
GB0425026D0 (en) 2004-11-12 2004-12-15 Biofocus Discovery Ltd Compounds which bind to the active site of protein kinase enzymes
US7741479B2 (en) 2004-12-07 2010-06-22 Locus Pharmaceuticals, Inc. Urea inhibitors of MAP kinases
CA2593718A1 (en) 2004-12-31 2007-05-31 Gpc Biotech Ag Napthyridine compounds as rock inhibitors
WO2006076706A1 (en) 2005-01-14 2006-07-20 Millennium Pharmaceuticals, Inc. Cinnamide and hydrocinnamide derivatives with raf-kinase inhibitory activity
WO2006086562A2 (en) 2005-02-09 2006-08-17 Microbia, Inc. Phenylazetidinone derivatives
WO2006127203A2 (en) 2005-05-25 2006-11-30 Wyeth Methods of synthesizing 6-alkylaminoquinoline derivatives
WO2007008942A2 (en) 2005-07-11 2007-01-18 Aerie Pharmaceuticals, Inc. Phenylamino-acetic acid [1-(pyridin-4-yl)-methylidene]-hydrazide derivatives and related compounds as modulators of g protein-coupled receptor kinases for the treatment of eye diseases
US7470787B2 (en) 2005-07-11 2008-12-30 Aerie Pharmaceuticals, Inc. Isoquinoline compounds
WO2007050783A2 (en) 2005-10-26 2007-05-03 Asahi Kasei Pharma Corporation Fasudil in combination therapies for the treatment of pulmonary arterial hypertension
TW200738682A (en) 2005-12-08 2007-10-16 Organon Nv Isoquinoline derivatives
BRPI0620463A2 (pt) 2005-12-22 2011-11-16 Alcon Res Ltd composição farmacêutica oftálmica, compostos, e seus usos
AR057252A1 (es) 2005-12-27 2007-11-21 Alcon Mfg Ltd Inhibicion de rho quinasa mediada por arni para el tratamiento de trastornos oculares
PE20071177A1 (es) 2005-12-30 2008-01-18 Novartis Ag Derivados de 3,5-piridina como inhibidores de renina
JP5476559B2 (ja) 2006-02-10 2014-04-23 国立大学法人九州大学 リン酸化酵素の新規基質ポリペプチド
JP2009528365A (ja) 2006-02-28 2009-08-06 アムゲン インコーポレイティッド ホスホジエステラーゼ１０阻害剤としてのシンノリン及びキナゾリン誘導体
JP2007246466A (ja) 2006-03-17 2007-09-27 Osaka Univ 中枢神経損傷に対する嗅粘膜移植にＲｈｏキナーゼ阻害剤を用いた神経機能再建法
TW200815398A (en) 2006-06-08 2008-04-01 Ube Industries A novel indazole derivative having spirocyclic structure in the side chain
WO2008011560A2 (en) 2006-07-20 2008-01-24 Mehmet Kahraman Benzothiophene inhibitors of rho kinase
US20090318485A1 (en) 2006-07-20 2009-12-24 Kalypsys, Inc. Novel inhibitors of rho kinase
BRPI0714782A2 (pt) 2006-07-31 2013-07-16 Senju Pharma Co preparaÇço lÍquida aquosa contendo composto de amida
EP2526948A1 (en) 2006-09-20 2012-11-28 Aerie Pharmaceuticals, Inc. RHO kinase inhibitors
WO2008054599A2 (en) 2006-09-27 2008-05-08 Surface Logix, Inc. Rho kinase inhibitors
US20090036465A1 (en) 2006-10-18 2009-02-05 United Therapeutics Corporation Combination therapy for pulmonary arterial hypertension
WO2008049919A2 (en) 2006-10-26 2008-05-02 Devgen N.V. Rho kinase inhibitors
US8071779B2 (en) 2006-12-18 2011-12-06 Inspire Pharmaceuticals, Inc. Cytoskeletal active rho kinase inhibitor compounds, composition and use
WO2008079945A2 (en) 2006-12-20 2008-07-03 University Of South Florida Rock inhibitors and uses thereof
AR064420A1 (es) 2006-12-21 2009-04-01 Alcon Mfg Ltd Composiciones farmaceuticas oftalmicas que comprenden una cantidad efectiva de analogos de 6-aminoimidazo[1,2b]piridazinas, utiles para el tratamiento del glaucoma y/o controlar la presion intraocular normal o elevada(iop).
MX2009005964A (es) 2006-12-27 2009-06-15 Sanofi Aventis Derivados de isoquinolina sustituidos con cicloalquilamina.
KR20090094338A (ko) 2006-12-27 2009-09-04 사노피-아벤티스 치환된 이소퀴놀린 및 이소퀴놀리논 유도체
JP5421783B2 (ja) 2006-12-27 2014-02-19 サノフイ Ｒｈｏキナーゼ阻害剤としての置換イソキノロン及びイソキノリノン誘導体
MX2009005862A (es) 2006-12-27 2009-06-17 Sanofi Aventis Nuevos derivados de isoquinolina e isoquinolinona sustituidos.
ES2364511T3 (es) 2006-12-27 2011-09-05 Sanofi Derivados de isoquinolona e isoquinolinona sustituidos con cicloalquilamina.
WO2008077551A1 (en) 2006-12-27 2008-07-03 Sanofi-Aventis Cycloalkylamine substituted isoquinolone derivatives
DK2102164T3 (da) 2006-12-27 2011-03-21 Sanofi Aventis Cycloalkylaminsubstituerede isochinolin- og isochinolinonderivater
US8455513B2 (en) 2007-01-10 2013-06-04 Aerie Pharmaceuticals, Inc. 6-aminoisoquinoline compounds
CA2683647A1 (en) 2007-04-10 2008-10-16 Boehringer Ingelheim International Gmbh Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
AR067413A1 (es) 2007-07-05 2009-10-07 Genentech Inc Compuestos heterociclicos que contienen ciclopenta[d]pirimidina inhibidores de proteinquinasas akt, composiciones farmaceuticas que los contienen, metodo de preparacion y uso de las mismas para el tratamiento de enfermedades hiperproliferativas, tales como cancer
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
US8450344B2 (en) 2008-07-25 2013-05-28 Aerie Pharmaceuticals, Inc. Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds
ES2834451T3 (es) * 2009-05-01 2021-06-17 Aerie Pharmaceuticals Inc Inhibidores de mecanismo doble para el tratamiento de enfermedades
EP2671586B1 (en) 2011-02-04 2018-05-30 Kowa Co., Ltd. Drug therapy for preventing or treating glaucoma
CN110396085B (zh) 2013-03-15 2024-11-15 爱尔康公司 联合治疗
WO2014143201A1 (en) 2013-03-15 2014-09-18 Demerx, Inc. Method for noribogaine treatment of addiction in patients on methadone
JP2017522324A (ja) 2014-07-17 2017-08-10 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングＭｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ 新規ナフチリジン及びイソキノリンならびにｃｄｋ８／１９阻害剤としてのその使用
US9643927B1 (en) 2015-11-17 2017-05-09 Aerie Pharmaceuticals, Inc. Process for the preparation of kinase inhibitors and intermediates thereof
WO2017086941A1 (en) 2015-11-17 2017-05-26 Aerie Pharmaceuticals, Inc. Process for the preparation of kinase inhibitors and intermediates thereof

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