CN109661396B - 作为rock抑制剂的螺稠合环状脲 - Google Patents

作为rock抑制剂的螺稠合环状脲 Download PDF

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Publication number
CN109661396B
CN109661396B CN201780054590.8A CN201780054590A CN109661396B CN 109661396 B CN109661396 B CN 109661396B CN 201780054590 A CN201780054590 A CN 201780054590A CN 109661396 B CN109661396 B CN 109661396B
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pyrazol
substituted
triazaspiro
independently selected
phenyl
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CN109661396A (zh
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R·S·拜德
M·S·保达斯
P·S·史鲁德
S·帕蒂尔
T·K·玛莎尔
K·泰亚加拉简
K·金纳科迪
P·W·格兰兹
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Bristol Myers Squibb Co
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    • 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
    • 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
    • A61K31/4174Arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole
    • 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
    • A61K31/41881,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
    • 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
    • A61K31/435Heterocyclic 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
    • A61K31/438The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
    • 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • 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
    • 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
    • C07D471/10Spiro-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
    • C07D487/10Spiro-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10Spiro-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Epidemiology (AREA)
  • Immunology (AREA)
  • Neurology (AREA)
  • Urology & Nephrology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Biomedical Technology (AREA)
  • Vascular Medicine (AREA)
  • Neurosurgery (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
CN201780054590.8A 2016-07-07 2017-07-06 作为rock抑制剂的螺稠合环状脲 Active CN109661396B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662359363P 2016-07-07 2016-07-07
US62/359,363 2016-07-07
PCT/US2017/040852 WO2018009627A1 (en) 2016-07-07 2017-07-06 Spiro-fused cyclic ureas as inhibitors of rock

Publications (2)

Publication Number Publication Date
CN109661396A CN109661396A (zh) 2019-04-19
CN109661396B true CN109661396B (zh) 2022-07-01

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US (1) US10787450B2 (https=)
EP (1) EP3481828B1 (https=)
JP (1) JP7155102B2 (https=)
KR (1) KR102449652B1 (https=)
CN (1) CN109661396B (https=)
ES (1) ES2829550T3 (https=)
WO (1) WO2018009627A1 (https=)

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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
WO2017205709A1 (en) 2016-05-27 2017-11-30 Bristol-Myers Squibb Company Triazolones and tetrazolones as inhibitors of rock
JP6903731B2 (ja) 2016-07-07 2021-07-14 ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company 強力で選択的なrock阻害剤としてのラクタム、環状尿素、およびカルバメート、およびトリアゾロン誘導体
JP7113810B2 (ja) 2016-07-07 2022-08-05 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ラクタム
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
WO2018227065A1 (en) * 2017-06-09 2018-12-13 Bristol-Myers Squibb Company Piperidinone formyl peptide 2 receptor and formyl peptide 1 receptor agonists
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
JP7234201B2 (ja) 2017-07-12 2023-03-07 ブリストル-マイヤーズ スクイブ カンパニー 心不全の治療のためのrockの5員アミノヘテロ環および5,6-または6,6員二環式アミノヘテロ環の阻害剤
US11447487B2 (en) 2017-07-12 2022-09-20 Bristol-Myers Squibb Company Spiroheptanyl hydantoins as rock inhibitors
US11306081B2 (en) 2017-07-12 2022-04-19 Bristol-Myers Squibb Company Phenylacetamides as inhibitors of rock
US12060341B2 (en) 2017-07-12 2024-08-13 Bristol-Myers Squibb Company Spiroheptanyl hydantoins as ROCK inhibitors
EP3704121B1 (en) 2017-11-03 2022-12-21 Bristol-Myers Squibb Company Diazaspiro rock inhibitors
MX2021005273A (es) 2018-11-06 2021-09-08 Cervello Therapeutics LLC Inhibidores de quinasa rock.
US11248004B2 (en) 2018-11-06 2022-02-15 Cervello Therapeutics, Llc. Substituted isoquinolines as rock kinase inhibitors
EP4431596A4 (en) 2021-11-11 2026-01-14 The Doshisha CRYOCONSERVATION PREPARATION FOR CORNIAL ENDOTHELIAL CELLS AND PROCESS FOR PRODUCING SAID CRYOCONSERVATION PREPARATION
AU2024265078A1 (en) 2023-05-04 2025-12-11 Revolution Medicines, Inc. Combination therapy for a ras related disease or disorder
IL326136A (en) 2023-08-07 2026-03-01 Revolution Medicines Inc RMC-6291 for use in the treatment of a disease or disorder associated with the RAS protein
US20250154171A1 (en) 2023-10-12 2025-05-15 Revolution Medicines, Inc. Ras inhibitors
WO2025171296A1 (en) 2024-02-09 2025-08-14 Revolution Medicines, Inc. Ras inhibitors
WO2025240847A1 (en) 2024-05-17 2025-11-20 Revolution Medicines, Inc. Ras inhibitors
US20250375445A1 (en) 2024-06-07 2025-12-11 Revolution Medicines, Inc. Methods of treating a ras protein-related disease or disorder
WO2025265060A1 (en) 2024-06-21 2025-12-26 Revolution Medicines, Inc. Therapeutic compositions and methods for managing treatment-related effects
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WO2014113620A2 (en) * 2013-01-18 2014-07-24 Bristol-Myers Squibb Company Phthalazinones and isoquinolinones as rock inhibitors
WO2014134391A1 (en) * 2013-02-28 2014-09-04 Bristol-Myers Squibb Company Phenylpyrazole derivatives as potent rock1 and rock2 inhibitors
CN105518005A (zh) * 2013-07-02 2016-04-20 百时美施贵宝公司 作为rock抑制剂的三环吡啶-甲酰胺衍生物

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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
WO2017205709A1 (en) 2016-05-27 2017-11-30 Bristol-Myers Squibb Company Triazolones and tetrazolones as inhibitors of rock
JP6903731B2 (ja) 2016-07-07 2021-07-14 ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company 強力で選択的なrock阻害剤としてのラクタム、環状尿素、およびカルバメート、およびトリアゾロン誘導体
ES2829550T3 (es) 2016-07-07 2021-06-01 Bristol Myers Squibb Co Ureas cíclicas espiro-condensadas como inhibidores de ROCK
JP7113810B2 (ja) 2016-07-07 2022-08-05 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ラクタム
KR102511441B1 (ko) 2016-11-30 2023-03-16 브리스톨-마이어스 스큅 컴퍼니 트리시클릭 Rho 키나제 억제제

Patent Citations (5)

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Publication number Priority date Publication date Assignee Title
WO2004050039A2 (en) * 2002-12-04 2004-06-17 Merck & Co., Inc. Spirocyclic ureas, compositions containing such compounds and methods of use
WO2012081665A1 (ja) * 2010-12-15 2012-06-21 大正製薬株式会社 グリシントランスポーター阻害物質
WO2014113620A2 (en) * 2013-01-18 2014-07-24 Bristol-Myers Squibb Company Phthalazinones and isoquinolinones as rock inhibitors
WO2014134391A1 (en) * 2013-02-28 2014-09-04 Bristol-Myers Squibb Company Phenylpyrazole derivatives as potent rock1 and rock2 inhibitors
CN105518005A (zh) * 2013-07-02 2016-04-20 百时美施贵宝公司 作为rock抑制剂的三环吡啶-甲酰胺衍生物

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US20190300528A1 (en) 2019-10-03
ES2829550T3 (es) 2021-06-01
KR20190025683A (ko) 2019-03-11
EP3481828A1 (en) 2019-05-15
US10787450B2 (en) 2020-09-29
KR102449652B1 (ko) 2022-09-29
WO2018009627A1 (en) 2018-01-11
JP7155102B2 (ja) 2022-10-18
EP3481828B1 (en) 2020-09-16
JP2019520396A (ja) 2019-07-18
CN109661396A (zh) 2019-04-19

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