CN107406426B - 作为rock抑制剂的环状脲类 - Google Patents

作为rock抑制剂的环状脲类 Download PDF

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Publication number
CN107406426B
CN107406426B CN201680012270.1A CN201680012270A CN107406426B CN 107406426 B CN107406426 B CN 107406426B CN 201680012270 A CN201680012270 A CN 201680012270A CN 107406426 B CN107406426 B CN 107406426B
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pyrazol
phenyl
imidazolidin
methoxybenzyl
pyridin
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Chinese (zh)
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CN107406426A (zh
Inventor
P.W.格伦斯
D.F.西特科夫
N.D.亚达夫
M.S.博达斯
R.S.比德
S.帕蒂尔
K.钦纳科蒂
P.S.M.劳
J.舍蒂
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Bristol Myers Squibb Co
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Bristol Myers Squibb Co
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • A61K31/41781,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42Oxazoles
    • A61K31/422Oxazoles not condensed and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/498Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/04Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/10Heterocyclic 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 carbon chain containing aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/10Heterocyclic 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 carbon chain containing aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
    • C07D413/10Heterocyclic 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 carbon chain containing aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/04Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Immunology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Transplantation (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
CN201680012270.1A 2015-01-09 2016-01-08 作为rock抑制剂的环状脲类 Active CN107406426B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201562101434P 2015-01-09 2015-01-09
US62/101434 2015-01-09
PCT/US2016/012560 WO2016112236A1 (en) 2015-01-09 2016-01-08 Cyclic ureas as inhibitors of rock

Publications (2)

Publication Number Publication Date
CN107406426A CN107406426A (zh) 2017-11-28
CN107406426B true CN107406426B (zh) 2020-11-20

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Country Status (8)

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US (1) US10123993B2 (enExample)
EP (1) EP3242873B1 (enExample)
JP (1) JP6779214B2 (enExample)
CN (1) CN107406426B (enExample)
AR (1) AR103990A1 (enExample)
ES (1) ES2815681T3 (enExample)
TW (1) TW201630899A (enExample)
WO (1) WO2016112236A1 (enExample)

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WO2016112236A1 (en) 2015-01-09 2016-07-14 Bristol-Myers Squibb Company Cyclic ureas as inhibitors of rock
WO2016144936A1 (en) 2015-03-09 2016-09-15 Bristol-Myers Squibb Company Lactams as inhibitors of rock
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AR107354A1 (es) 2016-01-13 2018-04-18 Bristol Myers Squibb Co Salicilamidas espiroheptanos y compuestos relacionados como inhibidores de rock
JP6987792B2 (ja) * 2016-05-27 2022-01-05 ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company Rock阻害剤としてのトリアゾロンおよびテトラゾロン
ES2821877T3 (es) 2016-07-07 2021-04-28 Bristol Myers Squibb Co Espirolactamas como inhibidores de ROCK
CN110049977B (zh) 2016-07-07 2022-01-18 百时美施贵宝公司 作为强效和选择性rock抑制剂的内酰胺、环状脲和氨基甲酸酯及三唑酮衍生物
ES2829550T3 (es) 2016-07-07 2021-06-01 Bristol Myers Squibb Co Ureas cíclicas espiro-condensadas como inhibidores de ROCK
KR102511441B1 (ko) * 2016-11-30 2023-03-16 브리스톨-마이어스 스큅 컴퍼니 트리시클릭 Rho 키나제 억제제
JP7206253B2 (ja) 2017-07-12 2023-01-17 ブリストル-マイヤーズ スクイブ カンパニー Rock阻害剤としてのフェニルアセトアミド
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
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
US12060341B2 (en) 2017-07-12 2024-08-13 Bristol-Myers Squibb Company Spiroheptanyl hydantoins as ROCK inhibitors
KR102680160B1 (ko) 2017-07-12 2024-06-28 브리스톨-마이어스 스큅 컴퍼니 심부전의 치료를 위한 rock의 5원-아미노헤테로사이클 및 5,6- 또는 6,6-원 비시클릭 아미노헤테로시클릭 억제제
WO2019089868A1 (en) * 2017-11-03 2019-05-09 Bristol-Myers Squibb Company Diazaspiro rock inhibitors
EP3886854A4 (en) 2018-11-30 2022-07-06 Nuvation Bio Inc. Pyrrole and pyrazole compounds and methods of use thereof
CN112759550A (zh) * 2019-11-04 2021-05-07 上海科技大学 一种平滑受体拮抗剂
JP2021183586A (ja) * 2020-05-22 2021-12-02 武田薬品工業株式会社 複素環化合物
WO2023085369A1 (ja) 2021-11-11 2023-05-19 学校法人同志社 角膜内皮細胞の凍結保存製剤およびその製造法
TW202508595A (zh) 2023-05-04 2025-03-01 美商銳新醫藥公司 用於ras相關疾病或病症之組合療法
CN119219603A (zh) * 2023-06-28 2024-12-31 科辉智药(深圳)新药研究中心有限公司 Sarm1酶活性抑制剂及其用途
WO2025034702A1 (en) 2023-08-07 2025-02-13 Revolution Medicines, Inc. Rmc-6291 for use in the treatment of ras protein-related disease or disorder
WO2025080946A2 (en) 2023-10-12 2025-04-17 Revolution Medicines, Inc. Ras inhibitors
CN120424050A (zh) * 2024-02-05 2025-08-05 科辉智药(深圳)新药研究中心有限公司 作为sarm1酶活性抑制剂的吡啶类化合物及其应用
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WO2014134388A1 (en) * 2013-02-28 2014-09-04 Bristol-Myers Squibb Company Phenylpyrazole derivatives as potent rock1 and rock2 inhibitors
WO2014134391A1 (en) * 2013-02-28 2014-09-04 Bristol-Myers Squibb Company Phenylpyrazole derivatives as potent rock1 and rock2 inhibitors
WO2015107053A1 (en) * 2014-01-20 2015-07-23 F. Hoffmann-La Roche Ag N-phenyl-lactam derivatives capable of stimulating neurogenesis and their use in the treatment of neurological disorders

Also Published As

Publication number Publication date
US20180000788A1 (en) 2018-01-04
JP6779214B2 (ja) 2020-11-04
TW201630899A (zh) 2016-09-01
ES2815681T3 (es) 2021-03-30
AR103990A1 (es) 2017-06-21
EP3242873B1 (en) 2020-07-22
WO2016112236A1 (en) 2016-07-14
US10123993B2 (en) 2018-11-13
CN107406426A (zh) 2017-11-28
EP3242873A1 (en) 2017-11-15
JP2018501285A (ja) 2018-01-18

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