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PE20211790A1 - SUBSTITUTE OXOPYRIDINE DERIVATIVES - Google Patents

SUBSTITUTE OXOPYRIDINE DERIVATIVES

Info

Publication number
PE20211790A1
PE20211790A1 PE2021000903A PE2021000903A PE20211790A1 PE 20211790 A1 PE20211790 A1 PE 20211790A1 PE 2021000903 A PE2021000903 A PE 2021000903A PE 2021000903 A PE2021000903 A PE 2021000903A PE 20211790 A1 PE20211790 A1 PE 20211790A1
Authority
PE
Peru
Prior art keywords
methyl
hydrogen
fluorine
oxetan
difluoromethyl
Prior art date
Application number
PE2021000903A
Other languages
Spanish (es)
Inventor
Susanne Rohrig
Sebastian Essig
Pascal Ellerbrock
Sonja Anlauf
Thomas Neubauer
Alexander Hillisch
Katharina Meier
Stefan Heitmeier
Adrian Tersteegen
Martina Schafer
Jan Stampfuss
Dieter Lang
Hongping Wang
Zengqiang Zou
Xianghai Meng
Kersten Matthias Gericke
Original Assignee
Bayer Ag
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 Bayer Ag filed Critical Bayer Ag
Publication of PE20211790A1 publication Critical patent/PE20211790A1/en

Links

Classifications

    • 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
    • C07D491/04Ortho-condensed systems
    • C07D491/044Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • 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
    • A61K31/4353Heterocyclic 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 ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

La invencion se refiere a compuestos derivados de oxopiridina sustituidos de formula (I); en donde R1 es metilo, etilo, difluorometilo o trifluorometilo; R2 es hidrogeno, metilo, difluorometilo o trifluorometilo, o R1 y R2 junto con los atomos de carbono a los cuales estan unidos forman un ciclobutilo; R3 es metilo, etilo o n-propilo, donde el metilo puede estar sustituido con un grupo seleccionado de ciclopropilo, ciclobutilo, oxetan-2-ilo, oxetan-3-ilo, tetrahidrofuran-2-ilo, entre otros; R4 es hidrogeno, R5 representa un grupo de la formula a), b), entre otros; R6 es hidrogeno, fluor o cloro, R7 es hidrogeno, fluor o cloro, R8 representa hidrogeno o fluor. Un compuesto seleccionado es acido 4-[(2S)-2-(11-cloro-7-metil-2-oxo-2,6,7,8-tetrahidro-3H-[3]benzoxocino[2,1-c]piridin-3-il)butanoil]amino}-2-fluorobenzamida. Tambien refiere a procesos para su preparacion. Dichos compuestos inhiben la escision enzimatica de sustratos FXIa, tales como el factor IX (FIX); siendo utiles en el tratamiento y/o la profilaxis de enfermedades, en particular trastornos vasculares, preferentemente trastornos tromboticos o tromboembolicos y/o complicaciones tromboticas o tromboembolicas.The invention relates to substituted oxopyridine derivative compounds of formula (I); wherein R1 is methyl, ethyl, difluoromethyl, or trifluoromethyl; R2 is hydrogen, methyl, difluoromethyl or trifluoromethyl, or R1 and R2 together with the carbon atoms to which they are attached form a cyclobutyl; R3 is methyl, ethyl or n-propyl, where methyl can be substituted with a group selected from cyclopropyl, cyclobutyl, oxetan-2-yl, oxetan-3-yl, tetrahydrofuran-2-yl, among others; R4 is hydrogen, R5 represents a group of formula a), b), among others; R6 is hydrogen, fluorine or chlorine, R7 is hydrogen, fluorine or chlorine, R8 represents hydrogen or fluorine. A selected compound is 4 - [(2S) -2- (11-chloro-7-methyl-2-oxo-2,6,7,8-tetrahydro-3H- [3] benzoxocino [2,1-c] acid pyridin-3-yl) butanoyl] amino} -2-fluorobenzamide. It also refers to processes for its preparation. Said compounds inhibit the enzymatic cleavage of FXIa substrates, such as factor IX (FIX); being useful in the treatment and / or prophylaxis of diseases, in particular vascular disorders, preferably thrombotic or thromboembolic disorders and / or thrombotic or thromboembolic complications.

PE2021000903A 2018-12-21 2019-12-18 SUBSTITUTE OXOPYRIDINE DERIVATIVES PE20211790A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN2018122825 2018-12-21
PCT/EP2019/085983 WO2020127504A1 (en) 2018-12-21 2019-12-18 Substituted oxopyridine derivatives

Publications (1)

Publication Number Publication Date
PE20211790A1 true PE20211790A1 (en) 2021-09-09

Family

ID=69143542

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2021000903A PE20211790A1 (en) 2018-12-21 2019-12-18 SUBSTITUTE OXOPYRIDINE DERIVATIVES

Country Status (22)

Country Link
EP (1) EP3898633A1 (en)
JP (1) JP2022514303A (en)
KR (1) KR20210106504A (en)
CN (1) CN113474348A (en)
AR (1) AR117435A1 (en)
AU (1) AU2019407909B2 (en)
BR (1) BR112021009435A2 (en)
CA (1) CA3124220A1 (en)
CL (1) CL2021001613A1 (en)
CO (1) CO2021007908A2 (en)
CR (1) CR20210342A (en)
DO (1) DOP2021000128A (en)
EA (1) EA202191764A1 (en)
EC (1) ECSP21043895A (en)
IL (1) IL283990A (en)
JO (1) JOP20210161A1 (en)
MA (1) MA54521A (en)
MX (1) MX2021007508A (en)
PE (1) PE20211790A1 (en)
SG (1) SG11202104384PA (en)
TW (1) TW202039510A (en)
WO (1) WO2020127504A1 (en)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
UA126940C2 (en) * 2018-03-15 2023-02-22 Баєр Акціенгезельшафт METHOD OF PREPARATION OF TWO 4-{[(2S)-2-{4-[5-CHLORO-2-(4-CHLORO-1H-1,2,3-TRIAZOL-1-YL)PHENYL]-5-METHOXY- 2-OXOPYRIDIN-1(2H)-YL}BUTANOYL]AMINO}-2-FLUOROBENZAMIDE
CN114105881B (en) 2020-08-31 2024-01-26 沈阳海诺威医药科技有限公司 Platelet aggregation inhibitor, and preparation method and application thereof
WO2022189280A1 (en) 2021-03-09 2022-09-15 Bayer Aktiengesellschaft Solvates of (4s)-24-chloro-4-ethyl-73-fluoro-35-methoxy-32,5-dioxo-14-(trifluoro-methyl)-32 h-6- aza-3(4,1)-pyridina-1(1)-[1,2,3]triazola-2(1,2),7(1)-dibenzenaheptaphane-74-carboxamide
WO2022189279A1 (en) 2021-03-09 2022-09-15 Bayer Aktiengesellschaft Crystalline forms of (4s)-24-chloro-4-ethyl-73-fluoro-35-methoxy-32,5-dioxo-14-(trifluoromethyl)-32h-6-aza-3(4,1)-pyridina-1(1)-[1,2,3]triazola-2(1,2),7(1)-5 dibenzenaheptaphane-74-carboxamide
CR20230431A (en) 2021-03-09 2023-10-27 Bayer Ag Pharmaceutical dosage forms comprising (4s)-24-chloro-4-ethyl-73-fluoro-35-methoxy-32,5- dioxo-14-(trifluoromethyl)-32h-6-aza-3(4,1)-pyridina-1(1)-[1,2,3]triazola-2(1,2),7(1)- dibenzenaheptaphane-74-carboxamide
CN114560754A (en) * 2022-02-25 2022-05-31 滁州学院 Preparation method of alkyl alcohol
WO2024223790A1 (en) * 2023-04-28 2024-10-31 Basf Se Use of alkyl 4-alkoxypentanoates as aroma chemicals
CN116874469B (en) * 2023-09-06 2023-11-10 成都施贝康生物医药科技有限公司 Oxo-pyridine compound, intermediate, preparation method and application thereof

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0420722D0 (en) 2004-09-17 2004-10-20 Addex Pharmaceuticals Sa Novel allosteric modulators
DE102006032824A1 (en) * 2006-07-14 2008-01-17 Bayer Healthcare Ag Substituted indazoles
US8163779B2 (en) 2006-12-20 2012-04-24 Takeda San Diego, Inc. Glucokinase activators
WO2014160592A2 (en) 2013-03-27 2014-10-02 Merck Sharp & Dohme Corp. FACTOR XIa INHIBITORS
TWI633089B (en) * 2013-03-28 2018-08-21 拜耳製藥股份有限公司 Substituted oxopyridine derivatives
CN105555767B (en) 2013-07-23 2018-03-23 拜耳制药股份公司 Substituted oxo pyridine derivative and its purposes as factor XI, plasma thromboplastin antecedent A/ blood plasma
CN105849109B (en) 2013-10-30 2018-01-23 拜耳制药股份公司 Substituted oxopyridine derivatives
EP3197889B1 (en) 2014-09-24 2018-08-01 Bayer Pharma Aktiengesellschaft Substituted oxopyridine derivatives
ES2712886T3 (en) * 2014-09-24 2019-05-16 Bayer Pharma AG Derivatives of pyridobenzazepine and pyridobenzazocine that inhibit factor XIa
WO2016046166A1 (en) 2014-09-24 2016-03-31 Bayer Pharma Aktiengesellschaft Substituted oxopyridine derivatives
EP3197880B1 (en) 2014-09-24 2018-10-24 Bayer Pharma Aktiengesellschaft Substituted oxopyridine derivatives with anti-inflammatory and anti-thrombotic effect
EP3197896B1 (en) 2014-09-24 2019-01-30 Bayer Pharma Aktiengesellschaft Substituted oxopyridine derivatives
CA2961981A1 (en) 2014-09-24 2016-03-31 Bayer Pharma Aktiengesellschaft Substituted oxopyridine derivatives
CA2979937A1 (en) 2015-03-19 2016-09-22 Bayer Pharma Aktiengesellschaft Oxo-pyridine-derivatives as factor xia inhibitors for the treatment of thrombosis
JO3703B1 (en) 2015-07-09 2021-01-31 Bayer Pharma AG Substituted oxopyridine derivatives
WO2017037051A1 (en) 2015-09-04 2017-03-09 Bayer Pharma Aktiengesellschaft Substituted oxopyridine derivatives

Also Published As

Publication number Publication date
AU2019407909B2 (en) 2023-05-25
JOP20210161A1 (en) 2023-01-30
KR20210106504A (en) 2021-08-30
EA202191764A1 (en) 2021-10-22
SG11202104384PA (en) 2021-05-28
MA54521A (en) 2022-03-30
CR20210342A (en) 2021-08-09
MX2021007508A (en) 2021-08-05
EP3898633A1 (en) 2021-10-27
WO2020127504A1 (en) 2020-06-25
AU2019407909A1 (en) 2021-05-27
ECSP21043895A (en) 2021-07-30
JP2022514303A (en) 2022-02-10
CL2021001613A1 (en) 2021-12-03
TW202039510A (en) 2020-11-01
CO2021007908A2 (en) 2021-07-19
BR112021009435A2 (en) 2021-08-17
DOP2021000128A (en) 2021-09-30
CN113474348A (en) 2021-10-01
CA3124220A1 (en) 2020-06-25
IL283990A (en) 2021-07-29
AR117435A1 (en) 2021-08-04

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