ES2722425T3 - (2H)-2-Oxopiridinas como inhibidores del factor XIa para el tratamiento de enfermedades trombóticas - Google Patents

(2H)-2-Oxopiridinas como inhibidores del factor XIa para el tratamiento de enfermedades trombóticas Download PDF

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ES2722425T3
ES2722425T3 ES15777625T ES15777625T ES2722425T3 ES 2722425 T3 ES2722425 T3 ES 2722425T3 ES 15777625 T ES15777625 T ES 15777625T ES 15777625 T ES15777625 T ES 15777625T ES 2722425 T3 ES2722425 T3 ES 2722425T3
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trifluoromethyl
difluoromethyl
fluorine
group
difluoromethoxy
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Susanne Röhrig
Eloisa Jimenez-Nunez
Karl-Heinz Schlemmer
Adrian Tersteegen
Henrik Teller
Alexander Hillisch
Stefan Heitmeier
Martina Victoria Schmidt
Jens Ackerstaff
Jan Stampfuss
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Bayer Pharma AG
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Bayer Pharma AG
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    • 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
    • C07D413/14—Heterocyclic 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
    • 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
    • C07D213/04—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 having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—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 having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • 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
    • C07D213/04—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 having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—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 having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • 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
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero 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
    • C07D413/12—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 chain containing hetero atoms as chain links

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Compuesto de fórmula **(Ver fórmula)** en la que R1 representa un grupo de fórmula **(Ver fórmula)** en la que * es el sitio de enlace al anillo de oxopiridina, R6 representa bromo, cloro, flúor, metilo, difluorometilo, trifluorometilo, metoxi, difluorometoxi, trifluorometoxi o metilamino, R7 representa bromo, cloro, flúor, ciano, nitro, hidroxi, metilo, difluorometilo, trifluorometilo, metoxi, etoxi, difluorometoxi, trifluorometoxi, etinilo, 3,3,3-trifluoroprop-1-in-1-ilo o ciclopropilo, R8 representa hidrógeno, cloro o flúor, R2 representa hidrógeno, bromo, cloro, flúor, ciano, alquilo C1-C3, difluorometilo, trifluorometilo, 1,1-difluoroetilo, 2,2-difluoroetilo, 2,2,2-trifluoroetilo, alcoxi C1-C3, difluorometoxi, trifluorometoxi, 1,1-difluoroetoxi, 2,2-difluoroetoxi, 2,2,2-trifluoroetoxi, metilcarbonilo o ciclopropilo, R3 representa hidrógeno, alquilo C1-C5, alcoxi C1-C4, difluorometilo, trifluorometilo, 1,1-difluoroetilo, 1,1,2,2,2- pentadeuteroetilo, 3,3,3-trifluoro-2-hidroxiprop-1-ilo, 3,3,3-trifluoro-2-metoxiprop-1-ilo, 3,3,3-trifluoro-2-etoxiprop- 1-ilo, prop-2-in-1-ilo, ciclopropiloxi o ciclobutiloxi, en el que alquilo puede estar sustituido con un sustituyente seleccionado del grupo que está constituido por flúor, ciano, hidroxi, difluorometilo, trifluorometilo, metoxi, etoxi, difluorometoxi, trifluorometoxi, cicloalquilo C3-C6, oxoheterociclilo de 4 a 6 miembros, 1,4-dioxanilo, oxazolilo, pirazolilo, oxadiazolilo, dihidro-oxazolilo, fenilo y piridilo, en el que cicloalquilo puede estar sustituido con 1 a 2 sustituyentes independientemente entre sí seleccionados del grupo que está constituido por flúor, hidroxi, metilo, etilo, metoxi, etoxi, difluorometilo, trifluorometilo, difluorometoxi y trifluorometoxi, y en el que oxo-heterociclilo puede estar sustituido con 1 a 2 sustituyentes independientemente entre sí seleccionados del grupo que está constituido por oxo, flúor, metilo, etilo, difluorometilo y trifluorometilo, y en el que oxazolilo, pirazolilo y oxadiazolilo pueden estar sustituidos con 1 a 2 sustituyentes independientemente entre sí seleccionados del grupo que está constituido por metilo y etilo, R4 representa hidrógeno, R5 representa un grupo de fórmula **(Ver fórmula)** en la que es el sitio de enlace al átomo de nitrógeno, R12 representa hidrógeno o flúor, R13 representa hidroxi o -NHR14, en el que R14 representa hidrógeno o alquilo C1-C4, o una de sus sales, sus solvatos o de los solvatos de sus sales.
ES15777625T 2014-09-24 2015-09-22 (2H)-2-Oxopiridinas como inhibidores del factor XIa para el tratamiento de enfermedades trombóticas Active ES2722425T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP14186084 2014-09-24
PCT/EP2015/071660 WO2016046166A1 (de) 2014-09-24 2015-09-22 Substituierte oxopyridin-derivate

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ES2722425T3 true ES2722425T3 (es) 2019-08-12

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ES15777625T Active ES2722425T3 (es) 2014-09-24 2015-09-22 (2H)-2-Oxopiridinas como inhibidores del factor XIa para el tratamiento de enfermedades trombóticas

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US (1) US10167280B2 (es)
EP (1) EP3197872B1 (es)
ES (1) ES2722425T3 (es)
WO (1) WO2016046166A1 (es)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2722423T3 (es) * 2014-09-24 2019-08-12 Bayer Pharma AG Derivados de oxopiridina sustituidos
CN107428689A (zh) * 2015-03-19 2017-12-01 拜耳制药股份公司 作为治疗血栓形成的因子xia抑制剂的氧代吡啶衍生物
JO3703B1 (ar) 2015-07-09 2021-01-31 Bayer Pharma AG مشتقات أوكسوبيريدين مستبدلة
CA3096480A1 (en) 2018-04-10 2019-10-17 Bayer Pharma Aktiengesellschaft A substituted oxopyridine derivative
ES2965494T3 (es) 2018-04-12 2024-04-15 Bayer Ag Derivados de N-(ciclopropilmetil)-5-(metilsulfonil)-n-{1-[1-(pirimidin-2-il)-1H-1,2,4-triazol-5-il]etil}benzamida y los correspondientes derivados de piridina-carboxamida como plaguicidas
WO2020127508A1 (en) 2018-12-21 2020-06-25 Bayer Aktiengesellschaft Substituted oxopyridine derivatives
WO2020127504A1 (en) 2018-12-21 2020-06-25 Bayer Aktiengesellschaft Substituted oxopyridine derivatives
JP7450024B2 (ja) * 2019-09-27 2024-03-14 シェンヅェン サルブリス ファーマシューティカルズ カンパニー リミテッド ＦＸＩａ阻害剤及びその調製方法と医薬用途
US11654036B2 (en) 2020-05-26 2023-05-23 Elixir Medical Corporation Anticoagulant compounds and methods and devices for their use
WO2022056326A1 (en) * 2020-09-11 2022-03-17 Elixir Medical Corporation Anticoagulant compounds, methods and devices for ophthalmic use
WO2022083707A1 (zh) * 2020-10-23 2022-04-28 深圳信立泰药业股份有限公司 FXIa抑制剂化合物或其盐的医药用途

Family Cites Families (9)

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EP1526131A1 (en) * 2003-10-22 2005-04-27 Graffinity Pharmaceuticals Aktiengesellschaft Aminoalkyl-pyrazinones and -pyridones as thrombin inhibitors
GB0420722D0 (en) 2004-09-17 2004-10-20 Addex Pharmaceuticals Sa Novel allosteric modulators
EP2091947A2 (en) 2006-12-20 2009-08-26 Takeda San Diego, Inc. Glucokinase activators
JP6033318B2 (ja) 2011-10-14 2016-11-30 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ 第ＸＩａ因子阻害剤としての置換テトラヒドロイソキノリン化合物
WO2014160592A2 (en) * 2013-03-27 2014-10-02 Merck Sharp & Dohme Corp. FACTOR XIa INHIBITORS
TWI633089B (zh) 2013-03-28 2018-08-21 拜耳製藥股份有限公司 經取代的酮基吡啶衍生物
EP3024822B1 (de) 2013-07-23 2017-05-03 Bayer Pharma Aktiengesellschaft Substituierte oxopyridin-derivate und ihre verwendung als faktor xia und plasmakallikrein inhibitoren
JP6368367B2 (ja) 2013-10-30 2018-08-01 バイエル ファーマ アクチエンゲゼルシャフト 置換オキソピリジン誘導体
EP3138839B1 (en) 2014-02-14 2020-10-28 Sichuan Haisco Pharmaceutical Co., Ltd. Pyridone or pyrimidone derivative, preparation method therefor and application thereof

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EP3197872B1 (de) 2019-01-30
WO2016046166A1 (de) 2016-03-31
EP3197872A1 (de) 2017-08-02
US20170291892A1 (en) 2017-10-12

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