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

Ｒｈｏキナーゼ阻害剤 Download PDF

Info

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
Authority
JP
Japan
Prior art keywords
oxo
dihydro
isoquinolin
chloro
phenyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
JP2009529306A
Other languages
English (en)
Japanese (ja)
Other versions
JP2010504342A (ja
JP2010504342A5 (enExample
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
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 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 filed Critical 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
Publication of JP2010504342A publication Critical patent/JP2010504342A/ja
Publication of JP2010504342A5 publication Critical patent/JP2010504342A5/ja
Application granted granted Critical
Publication of JP5235887B2 publication Critical patent/JP5235887B2/ja
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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

Landscapes

  • 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)
  • Engineering & Computer Science (AREA)
  • Ophthalmology & Optometry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (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 (enExample) 2010-08-26
JP5235887B2 true JP5235887B2 (ja) 2013-07-10

Family

ID=38740290

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2009529306A Expired - Fee Related JP5235887B2 (ja) 2006-09-20 2007-09-13 Ｒｈｏキナーゼ阻害剤

Country Status (9)

Country Link
US (5) US8809326B2 (enExample)
EP (2) EP2526948A1 (enExample)
JP (1) JP5235887B2 (enExample)
AR (1) AR062900A1 (enExample)
CA (1) CA2664335C (enExample)
CL (1) CL2007002686A1 (enExample)
ES (1) ES2729424T3 (enExample)
TW (1) TW200819133A (enExample)
WO (1) WO2008036540A2 (enExample)

Families Citing this family (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7470787B2 (en) 2005-07-11 2008-12-30 Aerie Pharmaceuticals, Inc. Isoquinoline compounds
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
JP5235887B2 (ja) 2006-09-20 2013-07-10 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 Ｒｈｏキナーゼ阻害剤
EP2066619A2 (en) * 2006-11-02 2009-06-10 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
AU2009262509B2 (en) * 2008-06-24 2014-01-30 Sanofi Bi-and polycyclic substituted isoquinoline and isoquinoline derivatives as Rho kinase inhibitors
US8450344B2 (en) 2008-07-25 2013-05-28 Aerie Pharmaceuticals, Inc. Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds
JP5937353B2 (ja) * 2008-08-19 2016-06-22 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプＪａｎｓｓｅｎ Ｐｈａｒｍａｃｅｕｔｉｃａ Ｎａａｍｌｏｚｅ Ｖｅｎｎｏｏｔｓｃｈａｐ 冷感−メントール受容体拮抗剤
WO2010126626A2 (en) 2009-05-01 2010-11-04 Aerie Pharmaceuticals, Inc. Dual mechanism inhibitors for the treatment of disease
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
WO2012054367A1 (en) 2010-10-19 2012-04-26 Boehringer Ingelheim International Gmbh Rho kinase inhibitors
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
JP6488239B2 (ja) 2013-01-18 2019-03-20 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ Ｒｏｃｋ阻害剤としてのフタラジノンおよびイソキノリノン
PT3811943T (pt) 2013-03-15 2023-03-15 Aerie Pharmaceuticals Inc Composto para uso no tratamento de distúrbios oculares
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
JP6683686B2 (ja) 2014-08-22 2020-04-22 オークランド ユニサービシーズ リミティド チャネル調節剤
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
US10787450B2 (en) 2016-07-07 2020-09-29 Bristol-Myers Squibb Company Spiro-fused cyclic ureas as inhibitors of rock
US11389441B2 (en) 2016-08-31 2022-07-19 Aerie Pharmaceuticals, Inc. Ophthalmic compositions
CA3057872A1 (en) 2017-03-31 2018-10-04 Aerie Pharmaceuticals, Inc. Aryl cyclopropyl-amino-isoquinolinyl amide compounds
KR102644889B1 (ko) 2017-07-12 2024-03-06 브리스톨-마이어스 스큅 컴퍼니 Rock 억제제로서의 스피로헵타닐 히단토인
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
US11306081B2 (en) 2017-07-12 2022-04-19 Bristol-Myers Squibb Company Phenylacetamides as inhibitors of rock
US11299488B2 (en) 2017-07-12 2022-04-12 Bristol-Myers Squibb Company Five membered-aminoheterocycle and 5,6-or 6,6-membered bicyclic aminoheterocyclic inhibitors of rock for the treatment of heart failure
KR102568375B1 (ko) * 2018-03-29 2023-08-18 김미희 RhoA 억제제 및 이의 용도
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
WO2022103899A1 (en) * 2020-11-10 2022-05-19 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
CA3238227A1 (en) 2021-11-11 2023-05-19 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
DK0389995T3 (da) 1989-03-28 1995-07-03 Nisshin Flour Milling Co Isoquinolinderivater til behandling af glaukom eller okular 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
JPH07504429A (ja) 1992-03-12 1995-05-18 スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー ５ＨＴ↓１ｃアンタゴニストとしてのインドール誘導体
DE4332168A1 (de) * 1993-02-22 1995-03-23 Thomae Gmbh Dr K Cyclische Derivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung
US5798380A (en) 1996-02-21 1998-08-25 Wisconsin Alumni Research Foundation Cytoskeletal active agents for glaucoma therapy
US6586425B2 (en) 1996-02-21 2003-07-01 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
WO2000076970A2 (en) 1999-06-14 2000-12-21 Eli Lilly And Company Serine protease inhibitors
HUP0302969A3 (en) 1999-11-26 2005-05-30 Shionogi & Co Npyy5 antagonists, pharmaceutical compositions containing them and their use
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
ES2341843T3 (es) 2000-02-03 2010-06-29 EISAI R&D MANAGEMENT CO., LTD. Inhibidores de la expresion de integrina.
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
US7361678B2 (en) 2002-03-05 2008-04-22 Transtech Pharma, Inc. Azole derivatives and fused bicyclic azole derivatives as therapeutic agents
US6323228B1 (en) 2000-09-15 2001-11-27 Abbott Laboratories 3-substituted indole angiogenesis inhibitors
WO2002032864A1 (en) 2000-10-17 2002-04-25 Applied Research Systems Ars Holding N.V. Pharmaceutically active sulfanilide derivatives
US7163800B2 (en) 2000-11-03 2007-01-16 Molecular Devices Corporation Methods of screening compositions for G protein-coupled receptor desensitization inhibitory activity
AU2002245590B2 (en) 2001-03-05 2006-06-29 Transtech Pharma, Inc. Benzimidazole derivatives as therapeutic agents
DE60218445T2 (de) 2001-04-20 2007-11-29 Bayer Pharmaceuticals Corp., West Haven Inhibierung der raf-kinase durch chinolin-, isochinolin- oder pyridin-harnstoffe
US6956035B2 (en) 2001-08-31 2005-10-18 Inotek Pharmaceuticals Corporation Isoquinoline derivatives and methods of use thereof
CA2472619A1 (en) 2002-01-10 2003-07-24 Bayer Corporation Fused pyrimidine derivates as rho-kinase inhibitors
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
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
DE60325719D1 (de) 2002-05-13 2009-02-26 Molecular Devices Corp Konstitutiv translozierende zelllinie
ES2382733T3 (es) 2002-08-29 2012-06-13 Santen Pharmaceutical Co., Ltd. Remedio para el glaucoma que comprende un inhibidor de la Rho quinasa y prostaglandinas
US7345158B2 (en) 2002-08-30 2008-03-18 Anges Mg, Inc. Actin related cytoskeletal protein “LACS”
CA2502583A1 (en) 2002-09-12 2004-03-25 Kirin Beer Kabushiki Kaisha Isoquinoline derivatives having kinase inhibitory activity and medicament containing the same
UY28213A1 (es) 2003-02-28 2004-09-30 Bayer Pharmaceuticals Corp Nuevos derivados de cianopiridina útiles en el tratamiento de cáncer y otros trastornos.
CA2526387A1 (en) 2003-06-12 2004-12-23 Astellas Pharma Inc. Benzamide derivative or salt thereof
JP5010917B2 (ja) 2003-08-29 2012-08-29 エグゼリクシス， インコーポレイテッド ｃ−Ｋｉｔ調節因子および使用方法
EP1689393A4 (en) 2003-10-06 2008-12-17 Glaxo Group Ltd PREPARATION OF 1,7-DISUBSTITUTED AZABENZIMIDAZOLES AS KINASE INHIBITORS
WO2005035506A1 (ja) 2003-10-15 2005-04-21 Ube Industries, Ltd. 新規インダゾール誘導体
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
JP2007008816A (ja) * 2003-10-15 2007-01-18 Ube Ind Ltd 新規イソキノリン誘導体
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
EP1718638A4 (en) 2004-02-20 2009-04-22 Smithkline Beecham Corp NEW 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
WO2006009889A1 (en) 2004-06-17 2006-01-26 Smithkline Beecham Corporation Novel inhibitors of rho-kinases
EP1810965A4 (en) 2004-10-13 2009-10-28 Eisai R&D Man Co Ltd HYDRAZIDE DERIVATIVES
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
JP2008523071A (ja) 2004-12-07 2008-07-03 ルーカス ファーマシューティカルズ， インコーポレイテッド Ｍａｐキナーゼの尿素インヒビター
EP1833832A1 (en) 2004-12-31 2007-09-19 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
AU2006249596A1 (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
ATE551059T1 (de) 2005-10-26 2012-04-15 Asahi Kasei Pharma Corp Fasudil in kombination mit bosentan zur behandlung von pulmonaler arterieller hypertonie
TW200738682A (en) 2005-12-08 2007-10-16 Organon Nv Isoquinoline derivatives
EP1962853A1 (en) 2005-12-22 2008-09-03 Alcon Research, Ltd. (indazol-5-yl)-pyrazines and (1,3-dihydro-indol-2-one)- pyrazines for treating rho kinase-mediated diseases and conditions
AR057252A1 (es) 2005-12-27 2007-11-21 Alcon Mfg Ltd Inhibicion de rho quinasa mediada por arni para el tratamiento de trastornos oculares
ES2430139T3 (es) 2005-12-30 2013-11-19 Novartis Ag Compuestos de piperidina 3,5-sustituido 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
MX2008010953A (es) 2006-02-28 2008-09-08 Amgen Inc Derivados de cinolina y quinoxalina como inhibidores de la fosfodiesterasa 10.
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
CA2653424A1 (en) 2006-06-08 2007-12-13 Ube Industries, Ltd. Novel indazole derivative having spiro ring structure in side chain
WO2008036459A2 (en) 2006-07-20 2008-03-27 Borchardt Allen J Inhibitors of rho kinase
CA2658764A1 (en) 2006-07-20 2008-01-24 Mehmet Kahraman Benzothiophene inhibitors of rho kinase
EP2050449A4 (en) 2006-07-31 2010-10-06 Senju Pharma Co AQUEOUS LIQUID PREPARATION WITH AN AMID COMPOUND
JP5235887B2 (ja) 2006-09-20 2013-07-10 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 Ｒｈｏキナーゼ阻害剤
CA2700988A1 (en) 2006-09-27 2008-05-08 Surface Logix, Inc. Rho kinase inhibitors
WO2008049000A2 (en) 2006-10-18 2008-04-24 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).
ATE502027T1 (de) 2006-12-27 2011-04-15 Sanofi Aventis Substituierte isochinoline und ihre verwendung als rho-kinase-inhibitoren
HRP20100705T1 (hr) 2006-12-27 2011-01-31 Sanofi-Aventis Cikloalkilaminski supstituirani izokinolinski i izokinolinonski derivati
CN101595094B (zh) 2006-12-27 2013-02-20 塞诺菲-安万特股份有限公司 环烷基胺取代的异喹诺酮衍生物
CA2673920C (en) 2006-12-27 2015-03-24 Sanofi-Aventis Cycloalkylamine substituted isoquinoline derivatives
MY148514A (en) 2006-12-27 2013-04-30 Sanofi Aventis Cycloalkylamine substituted isoquinolone and isoquinolinone derivatives
KR101517154B1 (ko) 2006-12-27 2015-04-30 사노피 Ｒｈｏ-키나제의 억제제로서의 치환된 이소퀴놀린 및 이소퀴놀리논 유도체
RU2009128693A (ru) 2006-12-27 2011-02-10 Санофи-Авентис (Fr) Замещенные производные изохинолина и изохинолинона
US8455513B2 (en) 2007-01-10 2013-06-04 Aerie Pharmaceuticals, Inc. 6-aminoisoquinoline compounds
WO2008124665A1 (en) 2007-04-10 2008-10-16 Boehringer Ingelheim International Gmbh Glucocorticoid mimetics, methods of making them, pharmaceutical compositions, and uses thereof
BRPI0813999A2 (pt) 2007-07-05 2019-10-01 Array Biopharma Inc ciclopentanos de pirimidil como inibidores de akt proteína cinase
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
WO2010126626A2 (en) 2009-05-01 2010-11-04 Aerie Pharmaceuticals, Inc. Dual mechanism inhibitors for the treatment of disease
TW202344254A (zh) 2011-02-04 2023-11-16 日商興和股份有限公司 青光眼或高眼壓症之預防或治療用之醫藥
PT3811943T (pt) 2013-03-15 2023-03-15 Aerie Pharmaceuticals Inc Composto para uso no tratamento de distúrbios oculares
CA2942638A1 (en) 2013-03-15 2014-09-18 Demerx, Inc. Method for noribogaine treatment of addiction in patients on methadone
WO2016009076A1 (en) 2014-07-17 2016-01-21 Merck Patent Gmbh Novel naphthryidines and isoquinolines and their use as cdk8/19 inhibitors
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

Also Published As

Publication number Publication date
CA2664335C (en) 2014-12-02
WO2008036540A3 (en) 2008-05-29
EP2068878A2 (en) 2009-06-17
US8809326B2 (en) 2014-08-19
EP2068878B1 (en) 2019-04-10
JP2010504342A (ja) 2010-02-12
US20180344723A1 (en) 2018-12-06
CL2007002686A1 (es) 2008-04-18
ES2729424T3 (es) 2019-11-04
US20080161297A1 (en) 2008-07-03
CA2664335A1 (en) 2008-03-27
AR062900A1 (es) 2008-12-10
US20160243102A1 (en) 2016-08-25
TW200819133A (en) 2008-05-01
EP2526948A1 (en) 2012-11-28
WO2008036540A2 (en) 2008-03-27
US10624882B2 (en) 2020-04-21
US20150297581A1 (en) 2015-10-22
US20140357652A1 (en) 2014-12-04

Similar Documents

Publication Publication Date Title
JP5235887B2 (ja) Ｒｈｏキナーゼ阻害剤
KR100757282B1 (ko) 아미드 유도체
US6218418B1 (en) 3(5)-amino-pyrazole derivatives, process for their preparation and their use as antitumor agents
EP2799435B1 (en) Poly (adp-ribose) polymerase inhibitor
RU2284187C2 (ru) Производные амида, способы их получения, фармацевтическая композиция, способ лечения
JP5799479B2 (ja) Ｒｈｏキナーゼインヒビター
RU2559895C2 (ru) Азотосодержащие производные гетероарилов
JP4857128B2 (ja) 新規な化合物
JP2019108346A (ja) リジン特異的なデメチラーゼ−１の阻害剤
WO2008086047A1 (en) Rho kinase inhibitors
NO329228B1 (no) Indoliziner som kinaseinhibitorer
JP2013531013A (ja) ＲｈｏキナーゼインヒビターとしてのＮ−環式−３−（環状カルボニルアミノメチル）ベンズアミド誘導体
JP2005519074A (ja) 治療用の置換インダゾール誘導体
CN103339108A (zh) 蛋白酶激活受体2(par2)拮抗剂
WO2018196757A1 (zh) 4-氨基嘧啶类化合物、其制备方法及应用
JPWO2017183723A1 (ja) Ｋｃｎｑ２〜５チャネル活性化剤
CN101006055B (zh) 作为酪蛋白激酶Iε抑制剂的3-取代的-5-和6-氨基烷基吲哚-2-羧酸酰胺以及相关类似物
JPH11152275A (ja) 含窒素縮合環化合物、その製造法および剤
HK40083035B (zh) Parp7抑制剂及其用途
HK1197679A (en) Poly (adp-ribose) polymerase inhibitor

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20100702

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20100702

A711 Notification of change in applicant

Free format text: JAPANESE INTERMEDIATE CODE: A711

Effective date: 20110610

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A821

Effective date: 20110610

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20121018

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20130118

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20130228

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20130326

R150 Certificate of patent or registration of utility model

Free format text: JAPANESE INTERMEDIATE CODE: R150

Ref document number: 5235887

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20160405

Year of fee payment: 3

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

LAPS Cancellation because of no payment of annual fees