JP6892858B2 - 第XIa因子阻害剤 - Google Patents

第XIa因子阻害剤 Download PDF

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Publication number
JP6892858B2
JP6892858B2 JP2018521211A JP2018521211A JP6892858B2 JP 6892858 B2 JP6892858 B2 JP 6892858B2 JP 2018521211 A JP2018521211 A JP 2018521211A JP 2018521211 A JP2018521211 A JP 2018521211A JP 6892858 B2 JP6892858 B2 JP 6892858B2
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mmol
mixture
alkyl
stirred
halo
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Japanese (ja)
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JP2018531954A5 (enExample
JP2018531954A (ja
Inventor
シュウ,ジァイ
アリ,アムジャド
チョウ,ウェイ
ギャオ,イン−デュオ
エドモンドソン,スコット・ディー
マーツ,エリック
ニーラムカヴィル,サントシュ・エフ
リュー,ウェイグォ
サン,ワンイーン
シェン,ドン−ミン
ハーパー,バート
シュウ,チェン
バラ,トーマス
リム,ヨン−ヒ
ヤン,メン
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Merck Sharp and Dohme LLC
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Merck Sharp and Dohme LLC
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    • 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
    • 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • 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
    • C07D401/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D413/14Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero 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
    • C07D471/08Bridged 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
    • 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
    • C07D487/08Bridged systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D513/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/08Bridged systems

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  • 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)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hematology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pyridine Compounds (AREA)
JP2018521211A 2015-10-29 2016-10-24 第XIa因子阻害剤 Active JP6892858B2 (ja)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201562248075P 2015-10-29 2015-10-29
US62/248,075 2015-10-29
PCT/US2016/058362 WO2017074832A1 (en) 2015-10-29 2016-10-24 FACTOR XIa INHIBITORS

Publications (3)

Publication Number Publication Date
JP2018531954A JP2018531954A (ja) 2018-11-01
JP2018531954A5 JP2018531954A5 (enExample) 2019-11-28
JP6892858B2 true JP6892858B2 (ja) 2021-06-23

Family

ID=58631804

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2018521211A Active JP6892858B2 (ja) 2015-10-29 2016-10-24 第XIa因子阻害剤

Country Status (12)

Country Link
US (1) US10214512B2 (enExample)
EP (1) EP3368036B1 (enExample)
JP (1) JP6892858B2 (enExample)
KR (1) KR102727485B1 (enExample)
CN (1) CN108430471B (enExample)
AU (1) AU2016344476B2 (enExample)
BR (1) BR112018008506B8 (enExample)
CA (1) CA2998902C (enExample)
MA (1) MA43128A (enExample)
MX (1) MX387515B (enExample)
RU (1) RU2728783C2 (enExample)
WO (1) WO2017074832A1 (enExample)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12344616B2 (en) 2018-10-25 2025-07-01 Merck Sharp & Dohme Llc Factor XIa inhibitors
EP3880673B1 (en) * 2018-11-13 2024-01-03 Novartis AG Compounds and compositions for treating conditions associated with nlrp activity
EP3957638B1 (en) 2019-04-16 2025-01-08 China Resources Biopharmaceutical Company Limited Macrocyclic derivatives acting as xia factor inhibitor
US20220281868A1 (en) * 2019-07-23 2022-09-08 Medshine Discovery Inc. Macrocyclic derivatives as factor xia inhibitors
MX2023000507A (es) * 2020-07-10 2023-02-09 Merck Sharp & Dohme Llc Inhibidores de la calicreina plasmatica.
EP4284367A4 (en) * 2021-01-28 2024-11-27 Merck Sharp & Dohme LLC FACTOR XIA INHIBITORS
US11814364B2 (en) 2021-03-18 2023-11-14 Janssen Pharmaceutica Nv Pyridine N-oxide derivatives useful as 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
US11919881B2 (en) 2021-03-18 2024-03-05 Janssen Pharmaceutica Nv Substituted pyridine N-oxide derivatives useful as a factor XIa inhibitors

Family Cites Families (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002037937A2 (en) 2000-11-07 2002-05-16 Bristol-Myers Squibb Company Acid derivatives useful as serine protease inhibitors
WO2002042273A2 (en) 2000-11-07 2002-05-30 Bristol-Myers Squibb Company Acid derivatives useful as serine protease inhibitors
HUP0304058A2 (hu) 2001-01-30 2004-04-28 Bristol-Myers Squibb Company Xa faktor szulfonamid-laktám inhibitorok és alkalmazásuk és ezeket tartalmazó gyógyszerkészítmények
AU2002331707A1 (en) 2001-08-20 2003-03-03 Bristol-Myers Squibb Company Tetrahydroquinoline derivatives as antithrombotic agents
EP1523483A4 (en) 2002-06-26 2006-03-08 Bristol Myers Squibb Co AMINO-BICYCLIC PYRAZINONE AND PYRIDINONE FOR INHIBITING THE COOKING OF SERIN PROTEASE
US20040180855A1 (en) 2003-02-19 2004-09-16 Schumacher William A. Methods of treating thrombosis with reduced risk of increased bleeding times
US7138412B2 (en) 2003-03-11 2006-11-21 Bristol-Myers Squibb Company Tetrahydroquinoline derivatives useful as serine protease inhibitors
US7129264B2 (en) 2003-04-16 2006-10-31 Bristol-Myers Squibb Company Biarylmethyl indolines and indoles as antithromboembolic agents
US7417063B2 (en) 2004-04-13 2008-08-26 Bristol-Myers Squibb Company Bicyclic heterocycles useful as serine protease inhibitors
US7453002B2 (en) 2004-06-15 2008-11-18 Bristol-Myers Squibb Company Five-membered heterocycles useful as serine protease inhibitors
US7429604B2 (en) 2004-06-15 2008-09-30 Bristol Myers Squibb Company Six-membered heterocycles useful as serine protease inhibitors
US20060074103A1 (en) 2004-10-06 2006-04-06 Corte James R Cyclic beta-amino acid derivatives as factor Xa inhibitors
ES2310861T3 (es) 2004-12-08 2009-01-16 Bristol-Myers Squibb Company Compuestos heterociclicos como inhibidores del factor viia.
ES2349428T3 (es) 2005-01-10 2011-01-03 Bristol-Myers Squibb Company Derivados de fenilglicinamida útiles como anticoagulantes.
JP5236293B2 (ja) 2005-01-13 2013-07-17 ブリストル−マイヤーズ スクイブ カンパニー Xia因子阻害剤としての置換ビアリール化合物
US20060183771A1 (en) 2005-02-17 2006-08-17 Seiffert Dietmar A Novel combination of selective factor VIIa and/or factor XIa inhibitors and selective plasma kallikrein inhibitors
CA2605480A1 (en) 2005-04-20 2006-11-02 Janssen Pharmaceutica N.V. Fluorinated pyridine n-oxide thrombin modulators and process for n-oxidation of nitrogen containing heteroaryls
AU2006325746A1 (en) 2005-12-14 2007-06-21 Bristol-Myers Squibb Company Six-membered heterocycles useful as serine protease inhibitors
WO2007070826A1 (en) 2005-12-14 2007-06-21 Bristol-Myers Squibb Company Arylpropionamide, arylacrylamide, arylpropynamide, or arylmethylurea analogs as factor xia inhibitors
US8466295B2 (en) 2005-12-14 2013-06-18 Bristol-Myers Squibb Company Thiophene derivatives as factor XIa inhibitors
US7829584B2 (en) * 2006-03-21 2010-11-09 Janssen Pharmaceutica Nv Pyridines and pyridine N-oxides as modulators of thrombin
CN101605779B (zh) 2006-12-15 2013-11-20 百时美施贵宝公司 作为凝血因子xia抑制剂的芳基丙酰胺、芳基丙烯酰胺、芳基丙炔酰胺或芳基甲基脲类似物
US8367709B2 (en) * 2007-06-13 2013-02-05 Bristol-Myers Squibb Company Dipeptide analogs as coagulation factor inhibitors
EP2265601B1 (en) 2008-03-13 2012-02-01 Bristol-Myers Squibb Company Pyridazine derivatives as factor xia inhibitors
CN102834397B (zh) 2010-02-11 2016-02-03 百时美施贵宝公司 作为凝血因子xia抑制剂的大环化合物
TW201311689A (zh) 2011-08-05 2013-03-16 必治妥美雅史谷比公司 作為因子xia抑制劑之新穎巨環化合物
TW201319068A (zh) 2011-08-05 2013-05-16 必治妥美雅史谷比公司 作為xia因子抑制劑之環狀p1接合劑
TWI586651B (zh) 2011-10-14 2017-06-11 必治妥美雅史谷比公司 作為因子xia抑制劑之經取代四氫異喹啉化合物
WO2013055984A1 (en) 2011-10-14 2013-04-18 Bristol-Myers Squibb Company Substituted tetrahydroisoquinoline compounds as factor xia inhibitors
IN2014CN02805A (enExample) 2011-10-14 2015-07-03 Bristol Myers Squibb Co
ES2765891T3 (es) 2011-12-21 2020-06-11 Ono Pharmaceutical Co Derivados de piridinona y pirimidinona como inhibidores del factor XIa
JP2015083542A (ja) 2012-02-08 2015-04-30 大日本住友製薬株式会社 3位置換プロリン誘導体
PT2880026T (pt) * 2012-08-03 2017-05-03 Bristol Myers Squibb Co Dihidropiridona p1 como inibidores de fator xia
ES2605824T3 (es) * 2012-08-03 2017-03-16 Bristol-Myers Squibb Company Dihidropiridona como inhibidores del factor XIa
WO2014160592A2 (en) 2013-03-27 2014-10-02 Merck Sharp & Dohme Corp. 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
US9663527B2 (en) * 2014-02-11 2017-05-30 Merck Sharp & Dohme Corp. Factor XIa inhibitors
WO2015157122A1 (en) * 2014-04-11 2015-10-15 The University Of North Carolina At Chapel Hill Mertk-specific pyrazolopyrimidine compounds
US9453018B2 (en) * 2014-10-01 2016-09-27 Bristol-Myers Squibb Company Pyrimidinones as factor XIa inhibitors
US20180162821A1 (en) * 2016-12-14 2018-06-14 Bristol-Myers Squibb Company Factor xia macrocycles with novel p1 groups

Also Published As

Publication number Publication date
KR20180073602A (ko) 2018-07-02
RU2018119015A3 (enExample) 2020-02-18
EP3368036A1 (en) 2018-09-05
CA2998902C (en) 2024-03-26
US10214512B2 (en) 2019-02-26
WO2017074832A1 (en) 2017-05-04
MA43128A (fr) 2018-09-05
AU2016344476B2 (en) 2020-08-13
EP3368036B1 (en) 2022-07-20
RU2018119015A (ru) 2019-11-29
BR112018008506A2 (pt) 2018-10-23
JP2018531954A (ja) 2018-11-01
MX2018005045A (es) 2018-08-01
CN108430471A (zh) 2018-08-21
MX387515B (es) 2025-03-18
KR102727485B1 (ko) 2024-11-06
RU2728783C2 (ru) 2020-07-31
EP3368036A4 (en) 2019-04-17
CN108430471B (zh) 2021-07-09
CA2998902A1 (en) 2017-05-04
US20180339977A1 (en) 2018-11-29
BR112018008506B1 (pt) 2023-11-14
BR112018008506B8 (pt) 2023-12-05
AU2016344476A1 (en) 2018-03-08

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