CN106413710A - 因子XIa抑制剂 - Google Patents

因子XIa抑制剂 Download PDF

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Publication number
CN106413710A
CN106413710A CN201580028124.3A CN201580028124A CN106413710A CN 106413710 A CN106413710 A CN 106413710A CN 201580028124 A CN201580028124 A CN 201580028124A CN 106413710 A CN106413710 A CN 106413710A
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CN
China
Prior art keywords
halogen
heteroaryl
cycloalkyl
aryl
mmol
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.)
Pending
Application number
CN201580028124.3A
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English (en)
Chinese (zh)
Inventor
刘卫国
S.D.埃蒙森
郭竹艳
E.默茨
A.K.奥加瓦
苏崇修
孙万莺
L.L.布罗库尼尔
A.阿利
邝荣泽
H.吴
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Merck Sharp and Dohme LLC
Original Assignee
Merck Sharp and Dohme LLC
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 Merck Sharp and Dohme LLC filed Critical Merck Sharp and Dohme LLC
Publication of CN106413710A publication Critical patent/CN106413710A/zh
Pending legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • A61K31/41—Heterocyclic 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
    • A61K31/4192—1,2,3-Triazoles
    • 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
    • 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
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
    • 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
    • C07D401/10—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 carbon chain containing aromatic rings
    • 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
    • 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
    • C07D413/10—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 carbon chain containing aromatic rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
CN201580028124.3A 2014-05-28 2015-05-22 因子XIa抑制剂 Pending CN106413710A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462003693P 2014-05-28 2014-05-28
US62/003693 2014-05-28
PCT/US2015/032091 WO2015183709A1 (en) 2014-05-28 2015-05-22 Factor xia inhibitors

Publications (1)

Publication Number Publication Date
CN106413710A true CN106413710A (zh) 2017-02-15

Family

ID=54699606

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201580028124.3A Pending CN106413710A (zh) 2014-05-28 2015-05-22 因子XIa抑制剂

Country Status (10)

Country Link
US (1) US9783530B2 (enExample)
EP (1) EP3148542B1 (enExample)
JP (1) JP2017517512A (enExample)
KR (1) KR20170005871A (enExample)
CN (1) CN106413710A (enExample)
AU (1) AU2015267305A1 (enExample)
CA (1) CA2947987A1 (enExample)
MX (1) MX2016015484A (enExample)
RU (1) RU2016150410A (enExample)
WO (1) WO2015183709A1 (enExample)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111763171A (zh) * 2019-04-02 2020-10-13 上海美悦生物科技发展有限公司 一种FXIa凝血因子抑制剂及其药物组合物、制备方法和医药用途
CN116348109A (zh) * 2020-09-17 2023-06-27 浙江海正药业股份有限公司 哌嗪类衍生物及其制备方法和用途

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2978751B1 (en) 2013-03-25 2018-12-05 Bristol-Myers Squibb Company Tetrahydroisoquinolines containing substituted azoles as factor xia inhibitors
UY35971A (es) 2014-01-31 2015-07-31 Bristol Myers Squibb Company Una Corporación Del Estado De Delaware Macrociclos con grupos p2? aromáticos como inhibidores del factor xia
NO2760821T3 (enExample) 2014-01-31 2018-03-10
US9975874B2 (en) 2014-07-28 2018-05-22 Merck Sharp & Dohme Corp. Factor XIa inhibitors
CN107074821B (zh) 2014-09-04 2020-05-22 百时美施贵宝公司 为fxia抑制剂的二酰胺大环化合物
US9453018B2 (en) 2014-10-01 2016-09-27 Bristol-Myers Squibb Company Pyrimidinones as factor XIa inhibitors
WO2016118403A1 (en) * 2015-01-20 2016-07-28 Merck Sharp & Dohme Corp. Factor xia inhibitors
EP3383847B1 (en) * 2015-12-02 2022-08-24 Merck Sharp & Dohme LLC FACTOR XIa INHIBITORS
US10143681B2 (en) 2016-08-22 2018-12-04 Merck Sharp & Dohme Corp. Factor XIa inhibitors
EP4036087A4 (en) * 2019-09-27 2023-09-20 Shenzhen Salubris Pharmaceuticals Co. Ltd Fxia inhibitors and preparation method therefor and pharmaceutical use thereof
US11919881B2 (en) 2021-03-18 2024-03-05 Janssen Pharmaceutica Nv Substituted pyridine N-oxide derivatives useful as a factor XIa inhibitors
US11845748B2 (en) 2021-03-18 2023-12-19 Janssen Pharmaceutica Nv Bicyclic pyridine N-oxide derivatives useful as a factor XIa inhibitors
US11814364B2 (en) 2021-03-18 2023-11-14 Janssen Pharmaceutica Nv Pyridine N-oxide derivatives useful as factor XIa inhibitors

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101228129A (zh) * 2005-04-20 2008-07-23 詹森药业有限公司 氟代吡啶n-氧化物凝血酶调节剂和含氮杂芳基化合物的n-氧化方法
CN101341124A (zh) * 2005-12-14 2009-01-07 布里斯托尔-迈尔斯斯奎布公司 可用作丝氨酸蛋白酶抑制剂的6元杂环
CN101784516A (zh) * 2007-06-13 2010-07-21 百时美施贵宝公司 作为凝血因子抑制剂的二肽类似物
US7829584B2 (en) * 2006-03-21 2010-11-09 Janssen Pharmaceutica Nv Pyridines and pyridine N-oxides as modulators of thrombin

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7429604B2 (en) * 2004-06-15 2008-09-30 Bristol Myers Squibb Company Six-membered heterocycles useful as serine protease inhibitors
US9161924B2 (en) * 2011-07-08 2015-10-20 Merck Sharp & Dohme Corp. Factor IXa inhibitors
EP3180317B1 (en) 2014-07-28 2021-04-14 Merck Sharp & Dohme Corp. FACTOR XIa INHIBITORS
US9975874B2 (en) 2014-07-28 2018-05-22 Merck Sharp & Dohme Corp. Factor XIa inhibitors
WO2016018701A1 (en) 2014-07-28 2016-02-04 Merck Sharp & Dohme Corp. FACTOR XIa INHIBITORS

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101228129A (zh) * 2005-04-20 2008-07-23 詹森药业有限公司 氟代吡啶n-氧化物凝血酶调节剂和含氮杂芳基化合物的n-氧化方法
CN101341124A (zh) * 2005-12-14 2009-01-07 布里斯托尔-迈尔斯斯奎布公司 可用作丝氨酸蛋白酶抑制剂的6元杂环
US7829584B2 (en) * 2006-03-21 2010-11-09 Janssen Pharmaceutica Nv Pyridines and pyridine N-oxides as modulators of thrombin
CN101784516A (zh) * 2007-06-13 2010-07-21 百时美施贵宝公司 作为凝血因子抑制剂的二肽类似物

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111763171A (zh) * 2019-04-02 2020-10-13 上海美悦生物科技发展有限公司 一种FXIa凝血因子抑制剂及其药物组合物、制备方法和医药用途
CN111763171B (zh) * 2019-04-02 2023-12-22 上海美悦生物科技发展有限公司 一种FXIa凝血因子抑制剂及其药物组合物、制备方法和医药用途
CN116348109A (zh) * 2020-09-17 2023-06-27 浙江海正药业股份有限公司 哌嗪类衍生物及其制备方法和用途

Also Published As

Publication number Publication date
US9783530B2 (en) 2017-10-10
MX2016015484A (es) 2017-03-23
JP2017517512A (ja) 2017-06-29
EP3148542A1 (en) 2017-04-05
CA2947987A1 (en) 2015-12-03
US20170197953A1 (en) 2017-07-13
WO2015183709A1 (en) 2015-12-03
AU2015267305A1 (en) 2016-11-03
EP3148542B1 (en) 2019-02-27
RU2016150410A (ru) 2018-06-28
EP3148542A4 (en) 2018-01-03
KR20170005871A (ko) 2017-01-16
RU2016150410A3 (enExample) 2018-11-30

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Application publication date: 20170215