JP5930278B2 - Ｍｌｋ阻害剤および使用方法 - Google Patents

Ｍｌｋ阻害剤および使用方法 Download PDF

Info

Publication number
JP5930278B2
JP5930278B2 JP2011537733A JP2011537733A JP5930278B2 JP 5930278 B2 JP5930278 B2 JP 5930278B2 JP 2011537733 A JP2011537733 A JP 2011537733A JP 2011537733 A JP2011537733 A JP 2011537733A JP 5930278 B2 JP5930278 B2 JP 5930278B2
Authority
JP
Japan
Prior art keywords
compound
mmol
pyrrolo
pyridin
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.)
Active
Application number
JP2011537733A
Other languages
English (en)
Japanese (ja)
Other versions
JP2012509903A (ja
JP2012509903A5 (show.php
Inventor
ゲルバード，ハリス，エー．
デフルスト，ステファン
グッドフェロー，ヴァル，エス．
ウイーマン，トルステン
コリン，ロヴェス
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of Rochester
Original Assignee
University of Rochester
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 University of Rochester filed Critical University of Rochester
Publication of JP2012509903A publication Critical patent/JP2012509903A/ja
Publication of JP2012509903A5 publication Critical patent/JP2012509903A5/ja
Application granted granted Critical
Publication of JP5930278B2 publication Critical patent/JP5930278B2/ja
Active 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • 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
    • A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • 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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and 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
    • A61K31/535—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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • 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
    • A61P27/16—Otologicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10—Antioedematous agents; Diuretics
    • 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
    • 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
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • A61P9/12—Antihypertensives
    • 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
    • A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—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
    • 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
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—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
    • 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
    • C07D471/10—Spiro-condensed systems
    • 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
    • C07D487/04—Ortho-condensed systems

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Hematology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Obesity (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Endocrinology (AREA)
  • Immunology (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Emergency Medicine (AREA)
  • Ophthalmology & Optometry (AREA)
  • Child & Adolescent Psychology (AREA)
  • Psychology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
JP2011537733A 2008-11-25 2009-11-25 Ｍｌｋ阻害剤および使用方法 Active JP5930278B2 (ja)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US11795008P 2008-11-25 2008-11-25
US61/117,950 2008-11-25
US14877809P 2009-01-30 2009-01-30
US14875509P 2009-01-30 2009-01-30
US61/148,778 2009-01-30
US61/148,755 2009-01-30
PCT/US2009/065878 WO2010068483A2 (en) 2008-11-25 2009-11-25 Mlk inhibitors and methods of use

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2014232195A Division JP5873544B2 (ja) 2008-11-25 2014-11-14 Ｍｌｋ阻害剤および使用方法

Publications (3)

Publication Number Publication Date
JP2012509903A JP2012509903A (ja) 2012-04-26
JP2012509903A5 JP2012509903A5 (show.php) 2013-01-17
JP5930278B2 true JP5930278B2 (ja) 2016-06-08

Family

ID=42243278

Family Applications (2)

Application Number Title Priority Date Filing Date
JP2011537733A Active JP5930278B2 (ja) 2008-11-25 2009-11-25 Ｍｌｋ阻害剤および使用方法
JP2014232195A Active JP5873544B2 (ja) 2008-11-25 2014-11-14 Ｍｌｋ阻害剤および使用方法

Family Applications After (1)

Application Number Title Priority Date Filing Date
JP2014232195A Active JP5873544B2 (ja) 2008-11-25 2014-11-14 Ｍｌｋ阻害剤および使用方法

Country Status (8)

Country Link
US (4) US8877772B2 (show.php)
EP (2) EP2379561B1 (show.php)
JP (2) JP5930278B2 (show.php)
CN (1) CN102264743B (show.php)
AU (1) AU2009324894B2 (show.php)
CA (1) CA2744498C (show.php)
ES (1) ES2554375T3 (show.php)
WO (1) WO2010068483A2 (show.php)

Families Citing this family (113)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8227603B2 (en) 2006-08-01 2012-07-24 Cytokinetics, Inc. Modulating skeletal muscle
US8299248B2 (en) 2006-08-02 2012-10-30 Cytokinetics, Incorporated Certain 1H-imidazo[4,5-b]pyrazin-2(3H)-ones and 1H-imidazo[4,5-b]pyrazin-2-ols and methods for their use
RS54542B1 (sr) 2006-08-02 2016-06-30 Cytokinetics, Inc. Određeni hemijski entiteti, kompozicije i metodi koji obuhvataju imidazopirimidine
EP2457913B1 (en) 2006-10-19 2017-04-19 Signal Pharmaceuticals, LLC Heteroaryl compounds, compositions thereof, and methods of treatment therewith
US7998976B2 (en) 2008-02-04 2011-08-16 Cytokinetics, Inc. Certain chemical entities, compositions and methods
CA2713864A1 (en) 2008-02-04 2009-08-13 Cytokinetics, Incorporated Certain chemical entities, compositions and methods
BRPI0917540A2 (pt) 2008-08-05 2015-11-17 Daiichi Sankyo Co Ltd composto, sal farmacologicamente aceitavél, composição farmacêutica, e, uso de um composto ou sal farmacologicamente aceitável
KR101712576B1 (ko) 2008-11-10 2017-03-06 버텍스 파마슈티칼스 인코포레이티드 Ａｔｒ 키나제의 억제제로서 유용한 화합물
EP2379561B1 (en) * 2008-11-25 2015-11-04 University Of Rochester Mlk inhibitors and methods of use
NZ593969A (en) 2008-12-19 2013-11-29 Vertex Pharma Pyrazine derivatives useful as inhibitors of atr kinase
CA2778615C (en) 2009-10-26 2019-04-23 Signal Pharmaceuticals, Llc Methods of synthesis and purification of heteroaryl compounds
US8962631B2 (en) 2010-05-12 2015-02-24 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
AU2011253021A1 (en) 2010-05-12 2012-11-29 Vertex Pharmaceuticals Incorporated 2 -aminopyridine derivatives useful as inhibitors of ATR kinase
WO2011143399A1 (en) 2010-05-12 2011-11-17 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
JP2013526540A (ja) 2010-05-12 2013-06-24 バーテックス ファーマシューティカルズ インコーポレイテッド Ａｔｒキナーゼ阻害剤として有用な化合物
SG185524A1 (en) 2010-05-12 2012-12-28 Vertex Pharma Compounds useful as inhibitors of atr kinase
US9062008B2 (en) 2010-05-12 2015-06-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
EP2576549A4 (en) * 2010-05-24 2013-12-18 Univ Rochester BICYCLIC HETEROARYLATES FORMING KINASE INHIBITORS AND METHODS OF USE
NZ605627A (en) * 2010-06-23 2015-06-26 Vertex Pharma Pyrrolo-pyrazine derivatives useful as inhibitors of atr kinase
DE102010049877A1 (de) 2010-11-01 2012-05-03 Merck Patent Gmbh 7-((1,2,3)Triazol-4-yl)-pyrrolo(2,3) pyrazinderivate
EP2487159A1 (en) 2011-02-11 2012-08-15 MSD Oss B.V. RorgammaT inhibitors
EP2694498B1 (en) 2011-04-05 2016-03-30 Vertex Pharmaceuticals Incorporated Aminopyrazine compounds useful as inhibitors of tra kinase
EP2723746A1 (en) 2011-06-22 2014-04-30 Vertex Pharmaceuticals Inc. Compounds useful as inhibitors of atr kinase
WO2012178123A1 (en) 2011-06-22 2012-12-27 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
JP2014522818A (ja) 2011-06-22 2014-09-08 バーテックス ファーマシューティカルズ インコーポレイテッド Ａｔｒキナーゼ阻害剤として有用な化合物
EA028060B1 (ru) 2011-07-13 2017-10-31 Сайтокинетикс, Инк. Комбинированная терапия бокового амиотрофического склероза
WO2013049859A1 (en) 2011-09-30 2013-04-04 Vertex Pharmaceuticals Incorporated Treating pancreatic cancer and non-small cell lung cancer with atr inhibitors
US8765751B2 (en) 2011-09-30 2014-07-01 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
MX353461B (es) 2011-09-30 2018-01-15 Vertex Pharma PROCESOS PARA PREPARAR COMPUESTOS ÚTILES COMO INHIBIDORES DE CINASA ATAXIA TELANGIECTASIA MUTADA Y Rad3 RELACIONADOS (ATR).
US8853217B2 (en) 2011-09-30 2014-10-07 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
WO2013049722A1 (en) 2011-09-30 2013-04-04 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
CA2852921C (en) * 2011-10-19 2023-10-10 Signal Pharmaceuticals, Llc Treatment of cancer with tor kinase inhibitors
EP2776420A1 (en) 2011-11-09 2014-09-17 Vertex Pharmaceuticals Incorporated Pyrazine compounds useful as inhibitors of atr kinase
EP2776429A1 (en) 2011-11-09 2014-09-17 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
JP2015502925A (ja) 2011-11-09 2015-01-29 バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ Ａｔｒキナーゼの阻害剤として有用なピラジン化合物
WO2013071088A1 (en) 2011-11-09 2013-05-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
EP2776422A1 (en) 2011-11-09 2014-09-17 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
SG11201402766UA (en) 2011-12-02 2014-06-27 Signal Pharm Llc PHARMACEUTICAL COMPOSITIONS OF 7-(6-(2-HYDROXYPROPAN-2-YL)PYRIDIN-3-YL)-1-((TRANS)-4-METHOXYCYCLOHEXYL)-3,4-DIHYDROPYRAZINO [2,3-<i>B</i>]PYRAZIN-2(1<i>H</i>)-ONE, A SOLID FORM THEREOF AND METHODS OF THEIR USE
WO2013126636A1 (en) 2012-02-24 2013-08-29 Signal Pharmaceuticals, Llc Methods for treating non- small cell lung cancer using tor kinase inhibitor combination therapy
CN102627646A (zh) * 2012-03-19 2012-08-08 苏州四同医药科技有限公司 一种3-碘-5-溴-4,7-二氮杂吲哚的制备方法
PT2833973T (pt) 2012-04-05 2017-12-21 Vertex Pharma Compostos úteis como inibidores da cinase atr e terapias de combinação dos mesmos
WO2014026329A1 (en) 2012-08-15 2014-02-20 Merck Sharp & Dohme Corp. N-alkylated indole and indazole compounds as rorgammat inhibitors and uses thereof
WO2014026330A1 (en) 2012-08-15 2014-02-20 Merck Sharp & Dohme Corp. 3-AMINOCYCLOALKYL COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF
WO2014026327A1 (en) 2012-08-15 2014-02-20 Merck Sharp & Dohme Corp. 4-heteroaryl substituted benzoic acid compounds as rorgammat inhibitors and uses thereof
DK2904406T3 (en) 2012-10-04 2018-06-18 Vertex Pharma METHOD OF DETERMINING THE ATR INHIBITION, INCREASED DNA DAMAGE
US8912198B2 (en) 2012-10-16 2014-12-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
AU2013203714B2 (en) 2012-10-18 2015-12-03 Signal Pharmaceuticals, Llc Inhibition of phosphorylation of PRAS40, GSK3-beta or P70S6K1 as a marker for TOR kinase inhibitory activity
WO2014080291A2 (en) 2012-11-21 2014-05-30 Rvx Therapeutics Inc. Biaryl derivatives as bromodomain inhibitors
US9073878B2 (en) 2012-11-21 2015-07-07 Zenith Epigenetics Corp. Cyclic amines as bromodomain inhibitors
EP2925319B1 (en) 2012-11-30 2019-01-09 University Of Rochester Mixed lineage kinase inhibitors for hiv/aids therapies
HK1209746A1 (en) 2012-12-07 2016-04-08 沃泰克斯药物股份有限公司 Compounds useful as inhibitors of atr kinase
US9260426B2 (en) 2012-12-14 2016-02-16 Arrien Pharmaceuticals Llc Substituted 1H-pyrrolo [2, 3-b] pyridine and 1H-pyrazolo [3, 4-b] pyridine derivatives as salt inducible kinase 2 (SIK2) inhibitors
US9271978B2 (en) 2012-12-21 2016-03-01 Zenith Epigenetics Corp. Heterocyclic compounds as bromodomain inhibitors
JP2016505041A (ja) 2013-01-16 2016-02-18 シグナル ファーマシューティカルズ，エルエルシー 置換型ピロロピリミジン化合物、その組成物、およびこれらを用いた治療方法
US9370515B2 (en) 2013-03-07 2016-06-21 Califia Bio, Inc. Mixed lineage kinase inhibitors and method of treatments
JP2016512815A (ja) 2013-03-15 2016-05-09 バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ Ａｔｒキナーゼの阻害剤として有用な縮合ピラゾロピリミジン誘導体
MX2015014455A (es) 2013-04-17 2016-07-21 Signal Pharm Llc Terapia de combinacion que comprende un inhibidor de tor cinasa y n-(3-(5-fluoro-2-(4-(2-metoxietoxi)fenilamino)pirimidin-4-ilamino )fenil)acrilamida para tratar cancer.
AU2014254053B2 (en) 2013-04-17 2019-06-06 Signal Pharmaceuticals, Llc Treatment of cancer with Dihydropyrazino-Pyrazines
SG10201801965RA (en) 2013-04-17 2018-04-27 Signal Pharm Llc Treatment of cancer with dihydropyrazino-pyrazines
CA2908957C (en) 2013-04-17 2021-05-18 Signal Pharmaceuticals, Llc Combination therapy comprising a dihydropyrazino-pyrazine compound and an androgen receptor antagonist for treating prostate cancer
US9474757B2 (en) 2013-04-17 2016-10-25 Signal Pharmaceuticals, Llc Methods for treating cancer using TOR kinase inhibitor combination therapy
US9359364B2 (en) 2013-04-17 2016-06-07 Signal Pharmaceuticals, Llc Pharmaceutical formulations, processes, solid forms and methods of use relating to 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b] pyrazin-2(1H)-one
WO2014172432A1 (en) 2013-04-17 2014-10-23 Signal Pharmaceuticals, Llc Combination therapy comprising a tor kinase inhibitor and a cytidine analog for treating cancer
WO2014181813A1 (ja) * 2013-05-10 2014-11-13 武田薬品工業株式会社 複素環化合物
CN105407892B (zh) 2013-05-29 2019-05-07 西格诺药品有限公司 一种化合物的药物组合物、其固体形式及它们的使用方法
CA2915622C (en) 2013-06-21 2020-08-18 Zenith Epigenetics Corp. Novel substituted bicyclic compounds as bromodomain inhibitors
SG11201510409QA (en) 2013-06-21 2016-01-28 Zenith Epigenetics Corp Novel bicyclic bromodomain inhibitors
US9855271B2 (en) 2013-07-31 2018-01-02 Zenith Epigenetics Ltd. Quinazolinones as bromodomain inhibitors
ES2768678T3 (es) 2013-12-06 2020-06-23 Vertex Pharma Compuesto de 2-amino-6-fluoro-N-[5-fluoro-piridin-3-il]pirazolo[1,5-a]pirimidin-3-carboxamida útil como inhibidor de la ATR quinasa, su preparación, diferentes formas sólidas y derivados radiomarcados de las mismas
US9512129B2 (en) 2014-04-16 2016-12-06 Signal Pharmaceuticals, Llc Solid forms comprising 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one and a coformer
NZ714742A (en) 2014-04-16 2017-04-28 Signal Pharm Llc Solid forms of 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one, compositions thereof and methods of their use
US9718824B2 (en) 2014-04-16 2017-08-01 Signal Pharmaceuticals, Llc Solid forms comprising 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one, and a coformer, compositions and methods of use thereof
ES2823756T3 (es) 2014-04-16 2021-05-10 Signal Pharm Llc Métodos para tratar el cáncer usando terapia de combinación de inhibidores de quinasa TOR
HRP20200186T1 (hr) 2014-06-05 2020-05-29 Vertex Pharmaceuticals Inc. Radioaktivno obilježeni derivati 2-amino-6-fluoro-n-[5-fluoro-piridin-3-il]-pirazolo[1,5-a]pirimidin-3-karboksamid spojeva koji se koriste kao inhibitori atr kinaze, priprava navedenih spojeva i njihovi različiti čvrsti oblici
PT3157566T (pt) 2014-06-17 2019-07-11 Vertex Pharma Método para tratamento de cancro utilizando uma combinação de inibidores chk1 e atr
NZ629796A (en) 2014-07-14 2015-12-24 Signal Pharm Llc Amorphous form of 4-((4-(cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7h-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-n-methylbenzamide, compositions thereof and methods of their use
EP3169686A4 (en) 2014-07-14 2018-01-24 Signal Pharmaceuticals, LLC Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
HUE049277T2 (hu) 2014-08-15 2020-09-28 Janssen Pharmaceuticals Inc Triazolok mint NR2B receptor inhibitorok
WO2016025918A1 (en) 2014-08-15 2016-02-18 Janssen Pharmaceuticals, Inc. Pyrazoles
EP3227281A4 (en) 2014-12-01 2018-05-30 Zenith Epigenetics Ltd. Substituted pyridinones as bromodomain inhibitors
US10179125B2 (en) 2014-12-01 2019-01-15 Zenith Epigenetics Ltd. Substituted pyridines as bromodomain inhibitors
HK1245248B (en) 2014-12-11 2020-05-15 恒翼生物医药(上海)股份有限公司 Substituted heterocycles as bromodomain inhibitors
HK1245247A1 (zh) 2014-12-17 2018-08-24 恒翼生物医药科技(上海)有限公司 溴结构域的抑制剂
WO2016130818A1 (en) 2015-02-11 2016-08-18 Merck Sharp & Dohme Corp. SUBSTITUTED PYRAZOLE COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF
WO2016164641A1 (en) * 2015-04-08 2016-10-13 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
BR112018000468A2 (pt) 2015-07-09 2018-09-18 Janssen Pharmaceutica Nv 4-azaindóis substituídos e seu uso como moduladores do receptor de glun2b
HK1258570A1 (zh) 2015-09-30 2019-11-15 Vertex Pharmaceuticals Inc. 使用dna损伤剂及atr抑制剂的组合治疗癌症的方法
JP2018535958A (ja) 2015-10-27 2018-12-06 メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． ＲＯＲγＴ阻害薬としての置換インダゾール化合物及びその使用
EP3368535B1 (en) 2015-10-27 2020-12-02 Merck Sharp & Dohme Corp. Heteroaryl substituted benzoic acids as rorgammat inhibitors and uses thereof
JP2018531957A (ja) 2015-10-27 2018-11-01 メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． ＲＯＲγＴ阻害薬としての置換二環式ピラゾール化合物及びその使用
SG11201806750WA (en) 2016-02-10 2018-09-27 Janssen Pharmaceutica Nv Substituted 1,2,3-triazoles as nr2b-selective nmda modulators
TW201819376A (zh) * 2016-10-06 2018-06-01 比利時商健生藥品公司 經取代之１Ｈ－咪唑並［４，５－ｂ］吡啶－２（３Ｈ）－酮及其作為ＧＬＵＮ２Ｂ受體調節劑之用途
US11447503B2 (en) 2019-06-14 2022-09-20 Janssen Pharmaceutica Nv Pyridine carbamates and their use as GLUN2B receptor modulators
BR112019027402A2 (pt) 2017-06-22 2020-07-07 Celgene Corporation tratamento de carcinoma hepatocelular caracterizado por infecção pelo vírus da hepatite b
WO2019169306A1 (en) 2018-03-01 2019-09-06 The Trustees Of Columbia University In The City Of New York Compounds, compositions, and methods for suppressing toxic endoplasmic reticulum stress
WO2019193516A2 (en) 2018-04-04 2019-10-10 Janssen Pharmaceutica Nv Substituted pyridine and pyrimidines and their use as glun2b receptor modulators
CN113015526A (zh) * 2018-09-19 2021-06-22 豪夫迈·罗氏有限公司 螺环2,3-二氢-7-氮杂吲哚化合物及其用途
EP3972606A4 (en) * 2019-05-20 2022-09-21 Mayo Foundation for Medical Education and Research TREATMENT OF CHRONIC LIVER DISEASE
PH12021552839A1 (en) 2019-06-14 2022-10-03 Janssen Pharmaceutica Nv Substituted pyrazolo-pyridine amides and their use as glun2b receptor modulators
KR20220020917A (ko) 2019-06-14 2022-02-21 얀센 파마슈티카 엔.브이. 치환된 피라졸로[4,3-b]피리딘 및 GLUN2B 수용체 조절제로서의 이들의 용도
TW202115054A (zh) 2019-06-14 2021-04-16 比利時商健生藥品公司 經取代的雜芳族吡唑并－吡啶及其作為ｇｌｕｎ２ｂ受體調節劑的用途
BR112021024117A2 (pt) 2019-06-14 2022-03-22 Janssen Pharmaceutica Nv Pirazolo-pirazinas substituídas e seu uso como moduladores do receptor de glun2b
CN113950357A (zh) 2019-06-14 2022-01-18 詹森药业有限公司 吡嗪氨基甲酸酯及其作为GluN2B受体调节剂的用途
CN113993868A (zh) 2019-06-14 2022-01-28 詹森药业有限公司 取代的吡唑并吡啶酰胺以及它们作为glun2b受体调节剂的用途
CN114555595B (zh) * 2019-08-30 2023-12-26 Tsd生命科学有限公司 咪唑并吡啶衍生物及将其作为有效成分的药学组合物
US12509430B2 (en) 2020-02-14 2025-12-30 President And Fellows Of Harvard College Inhibitors of nicotinamide N-methyltransferase, compositions and uses thereof
JP2023526521A (ja) * 2020-05-21 2023-06-21 ステムシナジー セラピューティクス， インク． Ｎｏｔｃｈ阻害剤及びそれらの使用
WO2023050323A1 (en) * 2021-09-30 2023-04-06 Citrix Systems, Inc. Automated transfer of peripheral device operations
US11479541B1 (en) 2022-01-31 2022-10-25 Pioneura Corporation Acid addition salts, compositions, and methods of treating thereof
US11661409B1 (en) * 2022-01-31 2023-05-30 Pioneura Corporation Acid addition salts, compositions, and methods of treating
CN116925106A (zh) * 2022-04-24 2023-10-24 上海医药集团股份有限公司 一种双环杂环化合物、药物组合物和应用
CN117050075A (zh) * 2022-05-05 2023-11-14 中国药科大学 一类联芳环类bet抑制剂及合成方法与用途
CN117447392B (zh) * 2023-09-13 2024-11-26 广州大学 一种荧光材料及其制备方法和应用

Family Cites Families (78)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4933438A (en) 1984-02-29 1990-06-12 University Of Florida Brain-specific analogues of centrally acting amines
US6150354A (en) 1987-01-15 2000-11-21 Bonnie Davis Compounds for the treatment of Alzheimer's disease
US5133974A (en) 1989-05-05 1992-07-28 Kv Pharmaceutical Company Extended release pharmaceutical formulations
ES2134215T3 (es) 1991-05-14 1999-10-01 Ernir Snorrason Tratamiento de sindromes de fatiga con inhibidores de colinesterasa.
IT1250421B (it) 1991-05-30 1995-04-07 Recordati Chem Pharm Composizione farmaceutica a rilascio controllato con proprieta' bio-adesive.
US6537579B1 (en) 1993-02-22 2003-03-25 American Bioscience, Inc. Compositions and methods for administration of pharmacologically active compounds
FR2710265B1 (fr) 1993-09-22 1995-10-20 Adir Composition pharmaceutique bioadhésive pour la libération contrôlée de principes actifs.
US5618819A (en) 1994-07-07 1997-04-08 Adir Et Compagnie 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one and oxazolo[4,5-b]pyridin-2-(3H)-one compounds
US6548084B2 (en) 1995-07-20 2003-04-15 Smithkline Beecham Plc Controlled release compositions
US6245347B1 (en) 1995-07-28 2001-06-12 Zars, Inc. Methods and apparatus for improved administration of pharmaceutically active compounds
DE19541260A1 (de) 1995-11-06 1997-05-07 Lohmann Therapie Syst Lts Therapeutische Zubereitung zur transdermalen Applikation von Wirkstoffen durch die Haut
US6512010B1 (en) 1996-07-15 2003-01-28 Alza Corporation Formulations for the administration of fluoxetine
ATE252892T1 (de) 1997-09-11 2003-11-15 Nycomed Danmark Aps Aus mehreren einzeleinheiten zusammengesetzte arzneimittel mit nicht-steroidalen wirkstoffen (nsaids)
US6624200B2 (en) 1998-08-25 2003-09-23 Columbia Laboratories, Inc. Bioadhesive progressive hydration tablets
US6607751B1 (en) 1997-10-10 2003-08-19 Intellipharamaceutics Corp. Controlled release delivery device for pharmaceutical agents incorporating microbial polysaccharide gum
GB9721437D0 (en) 1997-10-10 1997-12-10 Glaxo Group Ltd Heteroaromatic compounds and their use in medicine
US6403597B1 (en) 1997-10-28 2002-06-11 Vivus, Inc. Administration of phosphodiesterase inhibitors for the treatment of premature ejaculation
US6248864B1 (en) 1997-12-31 2001-06-19 Adherex Technologies, Inc. Compounds and methods and modulating tissue permeability
US6613358B2 (en) 1998-03-18 2003-09-02 Theodore W. Randolph Sustained-release composition including amorphous polymer
US6312717B1 (en) 1998-07-07 2001-11-06 Bristol-Myers Squibb Company Method for treatment of anxiety and depression
US20020009478A1 (en) 1998-08-24 2002-01-24 Douglas Joseph Dobrozsi Oral liquid mucoadhesive compositions
SE9802864D0 (sv) 1998-08-27 1998-08-27 Pharmacia & Upjohn Ab Transdermally administered tolterodine as antimuscarinic agent for the treatment of overactive bladder
ATE286725T1 (de) 1998-10-01 2005-01-15 Novartis Pharma Gmbh Neue oral anzuwendende arzneizubereitungen für rivastigmine mit kontrollierter wirkstoffabgabe
US6248363B1 (en) 1999-11-23 2001-06-19 Lipocine, Inc. Solid carriers for improved delivery of active ingredients in pharmaceutical compositions
US6498176B1 (en) 1999-03-04 2002-12-24 Smithklinebeecham Corporation 3-(anilinomethylene) oxindoles as protein tyrosine kinase and protein serine/threonine kinase inhibitors
GB9904933D0 (en) 1999-03-04 1999-04-28 Glaxo Group Ltd Compounds
GB9904995D0 (en) 1999-03-04 1999-04-28 Glaxo Group Ltd Substituted aza-oxindole derivatives
US6624171B1 (en) 1999-03-04 2003-09-23 Smithkline Beecham Corporation Substituted aza-oxindole derivatives
FR2792527B1 (fr) 1999-04-22 2004-08-13 Ethypharm Lab Prod Ethiques Microgranules de ketoprofene, procede de preparation et compositions pharmaceutiques
US6541020B1 (en) 1999-07-09 2003-04-01 Trimeris, Inc. Methods and compositions for administration of therapeutic reagents
WO2001005790A1 (en) 1999-07-21 2001-01-25 Astrazeneca Ab New compounds
US6562375B1 (en) 1999-08-04 2003-05-13 Yamanouchi Pharmaceuticals, Co., Ltd. Stable pharmaceutical composition for oral use
ATE376414T1 (de) 1999-09-02 2007-11-15 Nostrum Pharmaceuticals Inc Pellet formulierung mit gesteuerter freisetzung
US6544548B1 (en) 1999-09-13 2003-04-08 Keraplast Technologies, Ltd. Keratin-based powders and hydrogel for pharmaceutical applications
US6080736A (en) 1999-10-27 2000-06-27 Janus Pharmaceuticals, Inc. Methods and compositions for treating and preventing anxiety and anxiety disorders using optically pure (R) tofisopam
US6461631B1 (en) 1999-11-16 2002-10-08 Atrix Laboratories, Inc. Biodegradable polymer composition
AU2463701A (en) 1999-12-29 2001-07-09 Nanodelivery, Inc. Drug delivery system exhibiting permeability control
US6589549B2 (en) 2000-04-27 2003-07-08 Macromed, Incorporated Bioactive agent delivering system comprised of microparticles within a biodegradable to improve release profiles
US6524621B2 (en) 2000-05-01 2003-02-25 Aeropharm Technology Inc. Core formulation
US6482440B2 (en) 2000-09-21 2002-11-19 Phase 2 Discovery, Inc. Long acting antidepressant microparticles
US6524615B2 (en) 2001-02-21 2003-02-25 Kos Pharmaceuticals, Incorporated Controlled release pharmaceutical composition
WO2002070662A2 (en) 2001-03-02 2002-09-12 Gpc Biotech Ag Three hybrid assay system
US20030187026A1 (en) 2001-12-13 2003-10-02 Qun Li Kinase inhibitors
EP1599475A2 (en) * 2003-03-06 2005-11-30 Eisai Co., Ltd. Jnk inhibitors
GB2400101A (en) * 2003-03-28 2004-10-06 Biofocus Discovery Ltd Compounds capable of binding to the active site of protein kinases
CA2530589A1 (en) * 2003-07-02 2005-01-20 Sugen Inc. Arylmethyl triazolo and imidazopyrazines as c-met inhibitors
TWI339206B (en) 2003-09-04 2011-03-21 Vertex Pharma Compositions useful as inhibitors of protein kinases
TWI372624B (en) * 2004-03-30 2012-09-21 Vertex Pharma Azaindoles useful as inhibitors of jak and other protein kinases
US20060011139A1 (en) 2004-07-16 2006-01-19 Applied Materials, Inc. Heated substrate support for chemical vapor deposition
US7626021B2 (en) 2004-07-27 2009-12-01 Sgx Pharmaceuticals, Inc. Fused ring heterocycle kinase modulators
US7709645B2 (en) * 2004-07-27 2010-05-04 Sgx Pharmaceuticals, Inc. Pyrrolo-pyridine kinase modulators
CN101027302B (zh) * 2004-07-27 2011-05-11 Sgx药物公司 吡咯并吡啶激酶调节剂
KR20070053237A (ko) 2004-07-27 2007-05-23 에스지엑스 파마슈티컬스, 인코포레이티드 피롤로-피리딘 키나제 조절제
US7361764B2 (en) * 2004-07-27 2008-04-22 Sgx Pharmaceuticals, Inc. Pyrrolo-pyridine kinase modulators
AU2005289644A1 (en) 2004-09-24 2006-04-06 Janssen Pharmaceutica, N.V. Imidazo{4,5-b}pyrazinone inhibitors of protein kinases
EP1807425B1 (en) 2004-10-27 2014-07-30 Janssen Pharmaceutica NV Pyridine imidazoles and aza-indoles as progesterone receptor modulators
JP4954086B2 (ja) * 2004-12-08 2012-06-13 グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー １ｈ−ピロロ［２，３−ｂ］ピリジン
MX2007010068A (es) 2005-02-16 2007-10-10 Schering Corp Piperazino-piperidinas con actividad antagonista de cxcr3.
PT1893612E (pt) * 2005-06-22 2011-11-21 Plexxikon Inc Derivados de pirrolo [2,3-b]piridina como inibidores de proteína quinase
JP2007108926A (ja) 2005-10-12 2007-04-26 Denso Corp 運転支援装置及びプログラム
CA2629822A1 (en) 2005-12-08 2007-06-14 Irm Llc Methods and compositions for inhibiting hiv infection
EP2021496B1 (en) 2006-05-05 2010-08-11 George Mason Intellectual Properties, Inc. Methods for detecting hiv infection
JP2009537621A (ja) * 2006-05-22 2009-10-29 アストラゼネカ アクチボラグ インドール誘導体
US7732447B2 (en) * 2006-06-22 2010-06-08 Cephalon, Inc. Fused [d]pyridazin-7-ones
RS54542B1 (sr) 2006-08-02 2016-06-30 Cytokinetics, Inc. Određeni hemijski entiteti, kompozicije i metodi koji obuhvataju imidazopirimidine
EP2457913B1 (en) * 2006-10-19 2017-04-19 Signal Pharmaceuticals, LLC Heteroaryl compounds, compositions thereof, and methods of treatment therewith
GB0706168D0 (en) 2007-03-29 2007-05-09 Glaxo Group Ltd Compounds
AU2008237019A1 (en) 2007-04-10 2008-10-16 Sgx Pharmaceuticals, Inc. Fused ring heterocycle kinase modulators
AU2008241853B2 (en) 2007-04-18 2012-11-01 Kissei Pharmaceutical Co., Ltd. Nitrogenated fused ring derivative, pharmaceutical composition comprising the same, and use of the same for medical purposes
WO2009054941A1 (en) 2007-10-25 2009-04-30 Merck & Co., Inc. Therapeutic compounds
AU2009218607B2 (en) 2008-02-25 2014-02-13 F. Hoffmann-La Roche Ag Pyrrolopyrazine kinase inhibitors
BRPI0917540A2 (pt) * 2008-08-05 2015-11-17 Daiichi Sankyo Co Ltd composto, sal farmacologicamente aceitavél, composição farmacêutica, e, uso de um composto ou sal farmacologicamente aceitável
US8592448B2 (en) * 2008-11-20 2013-11-26 OSI Pharmaceuticals, LLC Substituted pyrrolo[2,3-b]-pyridines and -pyrazines
EP2379561B1 (en) * 2008-11-25 2015-11-04 University Of Rochester Mlk inhibitors and methods of use
US8846096B2 (en) 2008-12-12 2014-09-30 Creighton University Nanoparticles and methods of use
EP2576549A4 (en) 2010-05-24 2013-12-18 Univ Rochester BICYCLIC HETEROARYLATES FORMING KINASE INHIBITORS AND METHODS OF USE
EP2635260A4 (en) 2010-11-02 2014-07-09 Univ Nebraska COMPOSITIONS AND METHODS OF DELIVERING THERAPY AGENTS
EP2925319B1 (en) 2012-11-30 2019-01-09 University Of Rochester Mixed lineage kinase inhibitors for hiv/aids therapies

Also Published As

Publication number Publication date
WO2010068483A3 (en) 2010-09-30
JP2012509903A (ja) 2012-04-26
EP3037421A3 (en) 2016-11-30
CA2744498C (en) 2017-10-24
US8877772B2 (en) 2014-11-04
JP5873544B2 (ja) 2016-03-01
US9181247B2 (en) 2015-11-10
US20150105401A1 (en) 2015-04-16
JP2015052009A (ja) 2015-03-19
CN102264743B (zh) 2015-02-11
WO2010068483A2 (en) 2010-06-17
US9814704B2 (en) 2017-11-14
EP3037421A1 (en) 2016-06-29
EP2379561A2 (en) 2011-10-26
US20120053175A1 (en) 2012-03-01
AU2009324894A1 (en) 2011-11-24
US20160317509A1 (en) 2016-11-03
EP2379561B1 (en) 2015-11-04
AU2009324894B2 (en) 2015-04-09
ES2554375T3 (es) 2015-12-18
CN102264743A (zh) 2011-11-30
EP2379561A4 (en) 2012-10-03
US20160024087A1 (en) 2016-01-28
CA2744498A1 (en) 2010-06-17

Similar Documents

Publication Publication Date Title
JP5873544B2 (ja) Ｍｌｋ阻害剤および使用方法
JP6086326B2 (ja) 二環式ヘテロアリールキナーゼ阻害剤および使用方法
US11932643B2 (en) Substituted heterocyclic inhibitors of PTPN11
EP2925319B1 (en) Mixed lineage kinase inhibitors for hiv/aids therapies
US12186324B2 (en) Imidazopiperazine inhibitors of transcription activating proteins
CA3142239A1 (en) Anticancer combination therapy
US11046649B2 (en) Compounds useful as inhibitors of indoleamine 2,3-dioxygenase and/or tryptophan dioxygenase

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20121121

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20121122

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20140205

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20140206

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20140502

A602 Written permission of extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A602

Effective date: 20140513

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20140520

A02 Decision of refusal

Free format text: JAPANESE INTERMEDIATE CODE: A02

Effective date: 20140714

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20141114

A911 Transfer to examiner for re-examination before appeal (zenchi)

Free format text: JAPANESE INTERMEDIATE CODE: A911

Effective date: 20150202

A912 Re-examination (zenchi) completed and case transferred to appeal board

Free format text: JAPANESE INTERMEDIATE CODE: A912

Effective date: 20150220

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20160215

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20160420

R150 Certificate of patent or registration of utility model

Ref document number: 5930278

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250