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AR035068A1 - Compuestos de pirimidinona, composiciones farmaceuticas que los comprenden, uso de tales compuestos en la fabricacion de medicamentos y proceso para la preparacion de dichos compuestos - Google Patents

Compuestos de pirimidinona, composiciones farmaceuticas que los comprenden, uso de tales compuestos en la fabricacion de medicamentos y proceso para la preparacion de dichos compuestos

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Publication number
AR035068A1
AR035068A1 ARP010104761A ARP010104761A AR035068A1 AR 035068 A1 AR035068 A1 AR 035068A1 AR P010104761 A ARP010104761 A AR P010104761A AR P010104761 A ARP010104761 A AR P010104761A AR 035068 A1 AR035068 A1 AR 035068A1
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AR
Argentina
Prior art keywords
alkyl
mono
halogen
optionally substituted
compounds
Prior art date
Application number
ARP010104761A
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English (en)
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Smithkline Beecham Plc
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Application filed by Smithkline Beecham Plc filed Critical Smithkline Beecham Plc
Publication of AR035068A1 publication Critical patent/AR035068A1/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32One oxygen, sulfur or nitrogen atom
    • C07D239/34One oxygen atom
    • C07D239/36One oxygen atom as doubly bound oxygen atom or as unsubstituted hydroxy radical
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/06Antipsoriatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • 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
    • A61P9/10Drugs 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72Quinazolines; Hydrogenated quinazolines
    • C07D239/86Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/88Oxygen atoms
    • C07D239/91Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
    • 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
    • C07D401/12Heterocyclic 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
    • 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
    • C07D403/12Heterocyclic 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 chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D409/00Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur 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
    • C07D471/04Ortho-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
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D495/00Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Diabetes (AREA)
  • Rheumatology (AREA)
  • Neurosurgery (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Emergency Medicine (AREA)
  • Pain & Pain Management (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Hospice & Palliative Care (AREA)
  • Endocrinology (AREA)
  • Vascular Medicine (AREA)
  • Psychiatry (AREA)
  • Obesity (AREA)
  • Urology & Nephrology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Dermatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Compuestos de pirimidinona de fórmula (1) en donde: R1 es un grupo arilo, opcionalmente sustituido con 1, 2, 3 ó 4 sustituyentes que pueden ser iguales o diferentes seleccionados de alquilo C1-6, alcoxi C1-6, alquiltio C1-6, hidroxi, halógeno, CN, y mono a perfluoroalquilo C1-4; R2 es halógeno, alquilo C1-3, alcoxi C1-3, hidroxialquilo C1-3, alquiltio C1-3, alquilsulfinilo C1-3, aminoalquilo C1-3, mono- o dialquil C1-3aminoalquilo C1-3, alquil C1-3carbonilaminoalquilo C1-3, alcoxi C1-3alquil C1-3carbonilaminoalquilo C1-3, alquil C1-3sulfonilaminoalquilo C1-3, alquil C1-3carboxi, alquil C1-3carboxialquilo C1-3, y R3 es hidrógeno, halógeno, alquilo C1-3, o hidroxialquilo C1-3; o R2 y R3 junto con los átomos de C del anillo de pirimidona a los que están unidos forman un anillo carbocíclico condensado de 5- o 6-miembros; o R2 y R3 junto con los átomos de C del anillo de pirimidona a los que están unidos forman un anillo benzo o heteroarílico condensado, opcionalmente sustituido con 1, 2, 3 ó 4 sustituyentes, que pueden ser iguales o diferentes, seleccionados de halógeno, alquilo C1-4, ciano, alcoxi C1-6, alquil C1-6tio, o mono a perfluoroalquilo C1-4; R4 es hidrógeno, alquilo C1-6 que puede estar sustituido o no sustituido con 1, 2 ó 3 sustituyentes seleccionados de hidroxi, halógeno, OR7, COR7, carboxi, COOR7, CONR9R10, NR9R10, NR7COR8, mono. o di-(hidroxialquil C1-6)amino y N-hidroxialquil C1-6-N-alquil C1-6amino; o R4 es Het-alquilo C0-4 en el que Het es un anillo heterociclilo de 5- a 7-miembros que contiene N y opcionalmente O ó S, y en el que N puede estar sustituido con COR7, COOR7, CONR9R10, o alquilo C1-6 opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados de hidroxi, halógeno, OR7, COR7, carboxi, COOR7, CONR9R10 o NR9R10, por ejemplo, piperidin-4-ilo, pirrolidin-3-ilo; R5 es arilo o un anillo heteroarílico opcionalmente sustituido con 1, 2, 3 ó 4 sustituyentes que pueden ser iguales o diferentes seleccionados de alquilo C1-6, alcoxi C1-6, alquil C1-6tio, arilalcoxi C1-6, hidroxi, halógeno, CN, COR7, carboxi, COOR7, NR7COR8, CONR9R10, SO2NR9R10, NR7SO2R8, NR9R10, mono a perfluoroalquilo C1-4 y mono a perfluoroalcoxi C1-4; R6 es arilo o un anillo heteroarílico que está además opcionalmente sustituido con 1, 2, 3 ó 4 sustituyentes que pueden ser iguales o diferentes seleccionados de alquilo C1-18, alcoxi C1-18, alquil C1-6tio, alquil C1-6sulfonilo, arilalcoxi C1-6, hidroxi, halógeno, CN, COR7, carboxi, COOR7, CONR9R10, NR7COR8, SO2NR9R10, NR7SO2R8, NR9R10, mono a perfluoroalquilo C1-4 y mono a perfluoroalcoxi C1-4, o alquilo C5-10; R7 es hidrógeno o alquilo C1-12, por ejemplo alquilo C1-4 (v.g. metilo o etilo); R8 es hidrógeno, O-alquilo C1-6, o alquilo C1-12, por ejemplo alquilo C1-4 (v.g. metilo o etilo); R9 y R10 que pueden ser iguales o diferentes se seleccionan cada uno de hidrógeno, o alquilo C1-12, o R9 y R10 junto con el nitrógeno al que están unidos forman un anillo de 5- a 7-miembros que contiene opcionalmente uno o más heteroátomos adicionales seleccionados de oxígeno, nitrógeno y azufre, y está opcionalmente sustituido con 1 ó 2 sustituyentes seleccionados de hidroxi, oxo, alquilo C1-4, alquil C1-4carboxi, arilo, v.g. fenilo, o aralquilo, v.g. bencilo, ppor ejemplo, morfolina o piperazina; y X es alquileno C2-4, opcionalmente sustituido con 1, 2 ó 3 sustituyentes seleccionados de metilo, etilo, o CH=CH. Dichos compuestos tienen buena actividad como inhibidores de la enzima Lp-PLA2 y por lo tanto son útiles en terapia, en particular para el tratamiento de la ateroesclerosis. También se dan a conocer un proceso para su preparación, composiciones farmacéuticas que los comprenden, y el uso de tales compuestos en la fabricación de medicamentos.
ARP010104761A 2000-10-10 2001-10-10 Compuestos de pirimidinona, composiciones farmaceuticas que los comprenden, uso de tales compuestos en la fabricacion de medicamentos y proceso para la preparacion de dichos compuestos AR035068A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GBGB0024807.0A GB0024807D0 (en) 2000-10-10 2000-10-10 Novel compounds

Publications (1)

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AR035068A1 true AR035068A1 (es) 2004-04-14

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ARP010104761A AR035068A1 (es) 2000-10-10 2001-10-10 Compuestos de pirimidinona, composiciones farmaceuticas que los comprenden, uso de tales compuestos en la fabricacion de medicamentos y proceso para la preparacion de dichos compuestos

Country Status (11)

Country Link
US (2) US7169924B2 (es)
EP (1) EP1337517B1 (es)
JP (1) JP2004511473A (es)
AR (1) AR035068A1 (es)
AT (1) ATE415392T1 (es)
AU (1) AU2002223599A1 (es)
CA (1) CA2459746A1 (es)
DE (1) DE60136736D1 (es)
ES (1) ES2317949T3 (es)
GB (1) GB0024807D0 (es)
WO (1) WO2002030911A1 (es)

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ATE437862T1 (de) * 2000-02-16 2009-08-15 Smithkline Beecham Plc Pyrimidin-5-onderivate als ldl-pla2 inhibitoren
GB0024807D0 (en) * 2000-10-10 2000-11-22 Smithkline Beecham Plc Novel compounds
GB0119793D0 (en) * 2001-08-14 2001-10-03 Smithkline Beecham Plc Novel compounds
GB0127139D0 (en) * 2001-11-10 2002-01-02 Smithkline Beecham Novel compounds
GB0127140D0 (en) * 2001-11-10 2002-01-02 Smithkline Beecham Novel compounds
GB0208279D0 (en) * 2002-04-10 2002-05-22 Glaxo Group Ltd Novel compounds
GB0208280D0 (en) * 2002-04-10 2002-05-22 Glaxo Group Ltd Novel compounds
EP1735457A4 (en) 2004-04-16 2007-08-29 Glaxo Group Ltd METHODS FOR DETECTING Lp-PLA2 ACTIVITY AND INHIBITION OF Lp-PLA2 ACTIVITY
US20150017671A1 (en) 2004-04-16 2015-01-15 Yaping Shou Methods for detecting lp-pla2 activity and inhibition of lp-pla2 activity
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US7705005B2 (en) * 2006-10-13 2010-04-27 Glaxo Group Limited Bicyclic heteroaromatic compounds
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WO2008140449A1 (en) 2007-05-11 2008-11-20 Thomas Jefferson University Methods of treatment and prevention of neurodegenerative diseases and disorders
EP2155225B1 (en) * 2007-05-11 2015-07-08 The Trustees of the University of Pennsylvania Methods of treatment of skin ulcers
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AU2014210259B2 (en) 2013-01-25 2016-11-03 Glaxosmithkline Intellectual Property Development Limited Compounds
WO2014114249A1 (en) 2013-01-25 2014-07-31 Glaxosmithkline Intellectual Property Development Limited Bicyclic pyrimidone compounds as inhibitors of lp-pla2
US20140283157A1 (en) 2013-03-15 2014-09-18 Diadexus, Inc. Lipoprotein-associated phospholipase a2 antibody compositions and methods of use
WO2016012917A1 (en) 2014-07-22 2016-01-28 Glaxosmithkline Intellectual Property Development Limited 1,2,3,5-tetrahydroimidazo[1,2-c]pyrimidine derivatives useful in the treatment of diseases and disorders mediated by lp-pla2
WO2016012916A1 (en) 2014-07-22 2016-01-28 Glaxosmithkline Intellectual Property Development Limited 1,2,3,5-tetrahydroimidazo[1,2-c]pyrimidine derivatives useful in the treatment of diseases and disorders mediated by lp-pla2
CN107709314A (zh) 2015-06-11 2018-02-16 巴斯利尔药物国际股份公司 外排泵抑制剂及其治疗性用途
CN111825695B (zh) * 2019-04-15 2022-04-12 中国科学院上海药物研究所 噁唑烷酮类化合物、其制备方法、用途及其药物组合物
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CN115304620A (zh) 2021-05-07 2022-11-08 上海赛默罗生物科技有限公司 嘧啶酮衍生物、其制备方法、药物组合物和用途
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ATE437862T1 (de) * 2000-02-16 2009-08-15 Smithkline Beecham Plc Pyrimidin-5-onderivate als ldl-pla2 inhibitoren
GB0024807D0 (en) * 2000-10-10 2000-11-22 Smithkline Beecham Plc Novel compounds
US6649610B1 (en) * 2001-05-23 2003-11-18 University Of Central Florida 2-oxo-1, 4-benzoxazine compounds for treatment of tuberculosis

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US7462620B2 (en) 2008-12-09
US20040058941A1 (en) 2004-03-25
ES2317949T3 (es) 2009-05-01
JP2004511473A (ja) 2004-04-15
DE60136736D1 (de) 2009-01-08
EP1337517B1 (en) 2008-11-26
CA2459746A1 (en) 2002-04-18
EP1337517A1 (en) 2003-08-27
GB0024807D0 (en) 2000-11-22
US20060241126A1 (en) 2006-10-26
US7169924B2 (en) 2007-01-30
AU2002223599A1 (en) 2002-04-22
WO2002030911A1 (en) 2002-04-18
ATE415392T1 (de) 2008-12-15

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