AR039570A1 - Antagonistas de los receptores de trombina - Google Patents

Antagonistas de los receptores de trombina

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Publication number
AR039570A1
AR039570A1 ARP030101302A ARP030101302A AR039570A1 AR 039570 A1 AR039570 A1 AR 039570A1 AR P030101302 A ARP030101302 A AR P030101302A AR P030101302 A ARP030101302 A AR P030101302A AR 039570 A1 AR039570 A1 AR 039570A1
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Argentina
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alkyl
group
independently selected
alkoxy
cycloalkyl
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ARP030101302A
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English (en)
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Schering Corp
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First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=29250954&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR039570(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Schering Corp filed Critical Schering Corp
Publication of AR039570A1 publication Critical patent/AR039570A1/es

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    • 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
    • C07D405/06—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 carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • 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
    • 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
    • C07D417/14—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 three or more hetero rings

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Diabetes (AREA)
  • Neurosurgery (AREA)
  • Vascular Medicine (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Composiciones farmacéuticas que los contienen y un método para el tratamiento de enfermedades asociadas con trombosis, ateroesclerosis, restenosis, hipertensión, angina pectoris, arritmia, insuficiencia cardiaca, y cáncer administrando dichos compuestos. La terapia de combinación con otros agentes cardiovasculares es también reivindicada. Reivindicación 1: Un compuesto representado por la fórmula estructural (1), o una sal o solvato farmacéuticamente aceptable, en donde: la línea punteada simple representa un enlace simple opcional; y la línea punteada junto con la llena representa una doble ligadura opcional; n es 0-2; Q es una estructura del grupo de fórmulas (2), R1 es independientemente seleccionado del grupo consistente en H, alquilo (C1-6), fluoroalquilo (C1-6)-, difluoroalquilo (C1-6)-, trifluoro-alquilo (C1-6)-, cicloalquilo (C3-6), alquenilo (C2-6), hidroxi-alquilo (C1-6)-, y aminoalquilo (C1-6)-; R2 es independientemente seleccionado del grupo consistente en H, alquilo (C1-6), fluoroalquilo (C1-6)-, difluoroalquilo (C1-6)-, trifluoro-alquilo (C1-6)-, cicloalquilo (C3-6), alquenilo (C2-6), hidroxi-alquilo (C1-6)-, y aminoalquilo (C1-6)-; R3 es H, hidroxi, alcoxi (C1-6), -SOR16, -SO2R17, -C(O)OR17, -C(O)NR18R19, -alquilo (C1-6)-C(O)NR18R19, alquilo (C1-6), halógeno, fluoroalquilo (C1-6)-, difluoroalquilo (C1-6)-, trifluoroalquilo (C1-6)-, cicloalquilo (C3-6), cicloalquil (C3-6)-alquilo (C1-6)-, alquenilo (C2-6), ariloalquilo (C1-6)-, ariloalquenilo (C2-6)-, heteroariloalquilo (C1-6)-, heteroariloalquenilo (C2-6)-, hidroxialquilo (C1-6)-, -NR22R23R23, NR22R23-alquilo (C1-6)-, arilo, tioalquilo (C1-6)-, alquilo (C1-6)-tioalquilo (C1-6)-, alcoxi (C1-6)-alquilo (C1-6)-, NR18R19-C(O)-alquilo (C1-6)- o cicloalquilo (C3-6)-alquilo (C3-6)-; Het es heteroarilo un grupo mono- o bi-cíclico de 5 a 10 átomos comprendiendo de 1 a 9 átomos de carbono y 1 a 4 heteroátomos independientemente seleccionados del grupo consistente en N, O y S, donde un nitrógeno del anillo puede formar un N-oxido o un grupo cuaternario con un grupo alquilo (C1-4), donde Het está unido a B por un átomo de carbono miembro del anillo, y donde el grupo Het está substituido por W; W es 1 a 4 substituyentes independientemente seleccionados del grupo consistente en H, alquilo (C1-6), fluoroalquilo (C1-6)-, difluoroalquilo (C1-6)-, trifluoroalquilo (C1-6)-, cicloalquilo (C3-6), hidroxialquilo (C1-6)-, dihidroxialquilo (C1-6)-, NR25R26alquilo (C1-6)-, tioalquilo (C1-6)-, -OH, alcoxi (C1-6), halógeno, -NR4R5, -C(O)OR17, -COR16, alquiltio (C1-6)-, R21-arilo, R21-ariloalquilo (C1-6)-, arilo donde los carbonos adyacentes forman un anillo que comprende un grupo metilendioxi, y R21-heteroarilo; R4 y R5 son independientemente seleccionados del grupo consistente en H, alquilo (C1-6), fenilo, bencilo y cicloalquilo (C3-6), o R4 y R5 tomados juntos son -(CH2)4-, -(CH2)5- o -(CH2)2NR7-(CH2)2- y forman un anillo con el nitrógeno al cual ellos están unidos; R6 es H, alquilo (C1-6) o fenilo; R7 es H, alquilo (C1-6), -C(O)-R16, -C(O)OR17 o -SO2R17; R8, R10 y R11 son independientemente seleccionados del grupo consistente en R1 y -OR1, siempre que cuando el doble enlace opcional está presente, R10 está ausente; R9 es H, OH o alcoxi (C1-6); B es -(CH2)n3-, cis o trans -(CH2)n4CR12-CR12a(CH2)n5- o -(CH2)n4Cs(CH2)n5-, donde n3 es 0-5, n4 y n5 son independientemente 0-2, y R12 y R12a son independientemente seleccionados del grupo consistente en H, alquilo (C1-6) y halógeno; X es -O- o -NR6- cuando la línea punteada representa un enlace simple, o X es -OH o -NHR20 cuando el enlace está ausente; Y es =O, =S, (H, H), (H, OH) o (H, alcoxi (C1-6)) cuando la línea punteada representa un enlace simple, o cuando el enlace está ausente, Y es =O, (H, H), (H, OH), (H, SH) o (H, alcoxi(C1-6)); cada R13 es independientemente seleccionado de H, alquilo (C1-6), cicloalquilo (C3-8), -(CH2)n6NHC(O)OR16b, -(CH2)n6NHC(O)R16b, -(CH2)n6NHC(O)NR4R5, -(CH2)n6NHSO2R16, -(CH2)n6NHSO2NR4R5, y -(CH2)n6C(O)NR28R29 donde n6 es 0-4, haloalquilo, y halógeno; cada R14 es independientemente seleccionado entre H, alquilo (C1-6), -OH, alcoxi (C1-6), R27-ariloalquilo (C1-6), heteroarilo, heteroariloalquilo, heterociclilo, heterociclilalquilo, -(CH2)n6NHC(O)OR16b, -(CH2)n6NHC(O)R16b, -(CH2)n6NHC(O)NR4R5, -(CH2)n6NHSO2R16, -(CH2)n6NHSO2NR4R5, y -(CH2)n6C(O)NR28R29 donde n6 es 0-4, halógeno y haloalquilo; o R13 y R14 tomados juntos forman un anillo espirocíclico o heterospirociclico de 3-6 átomos; donde al menos uno de R13 o R14 es seleccionado del grupo consistente en -(CH2)n6NHC(O)OR16b, -(CH2)n6NHC(O)R16b, -(CH2)n6NHC(O)NR4R5, -(CH2)n6NHSO2R16, -(CH2)n6NHSO2NR4R5, y -(CH2)n6C(O)NR28R29 donde n6 es 0-4; R15 está ausente cuando la línea punteada representa un enlace simple y es H, alquilo (C1-6), -NR18R19, o -OR17 cuando el enlace está ausente; R16 es independientemente seleccionado del grupo consistente en alquilo (C1-6), fenilo y bencilo; R16b es H, alcoxi, alquilo (C1-6), alcoxi (C1-6)-alquilo (C1-6)-, R22-O-C(O)-alquilo (C1-6)-, cicloalquilo (C3-6), R21-arilo, R21-arilalquilo (C1-6), haloalquilo, alquenilo, halosubstituido alquenilo, alquinilo, alquinilo halosubstituido, R21-heteroarilo, R21-alquilo (C1-6) heteroarilo, R21-alquilo (C1-6) heterocicloalquilo, R28R29N-alquilo (C1-6), R28R29N-(CO)-alquilo (C1-6), R28R29N-(CO)O-alquilo (C1-6), R28O(CO)N(R29)-alquilo (C1-6), R28S(O)2N(R29)-alquilo (C1-6), R28R29N-(CO)-N(R29)-alquilo (C1-6), R28R2N-S(O)2N(R29)-alquilo (C1-6), R28-(CO)N(R29)-alquilo (C1-6), R28R29N-S(O)2-alquilo (C1-6), HOS(O)2-alquilo (C1-6), (OH)2P(O)2-alquilo (C1-6), R28-S-alquilo (C1-6), R28-S(O)2-alquilo (C1-6) o hidroxialquilo (C1-6); R17, R18 y R19 son independientemente seleccionados del grupo consistente en H, alquilo (C1-6), fenilo, y bencilo; R20 es H, alquilo(C1-6), fenilo, bencilo, -C(O)R6 o -SO2R6; R21 es 1 a 3 sustituyentes independientemente seleccionado del grupo consistente en H, -CN, -CF3, -OCF3, halógeno, -NO2, alquilo (C1-6), -OH, alcoxi (C1-6), alquilo (C1-6)amino-, di-(alquilo (C1-6))amino-, NR25R26-alquilo (C1-6)-, hidroxi-alquilo (C1-6)-, -C(O)OR17, -C(O)R17, -NHCOR16, -NHSO2R16, -NHSO2CH2CF3, -C(O)NR25R2, -NR25-C(O)-NR25R26, -S(O)R13, -S(O)2R13 y -SR13; R22 es H o alquilo (C1-6); R23 es H, alquilo (C1-6), -SO2R24, -C(O)NHR24 o -SO2NHR24; R24 es alquilo (C1-6), hidroxi alquilo (C1-6) o NR25R26-(alquilo (C1-6))-; R25 y R26 son independientemente seleccionados del grupo consistente en H y alquilo (C1-6); R27 es 1, 2 o 3 substituyentes seleccionados del grupo consistente en H, alquilo (C1-6), cicloalquilo (C3-6), alcoxi (C1-6), halógeno y -OH; y R28 y R29 son independientemente seleccionados del grupo consistente en H, alquilo (C1-6), alcoxi (C1-6), R27-ariloalquilo (C1-6), heteroarilo, heteroariloalquilo, hidroxialquilo (C1-6), alcoxi (C1-6)-alquilo (C1-6), heterociclilo, heterociclilalquilo, y haloalquilo; o R28 y R29 tomados juntos forman un anillo espirociclico o heterospirociclico de 3-6 átomos.
ARP030101302A 2002-04-16 2003-04-14 Antagonistas de los receptores de trombina AR039570A1 (es)

Applications Claiming Priority (1)

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US37307202P 2002-04-16 2002-04-16

Publications (1)

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AR039570A1 true AR039570A1 (es) 2005-02-23

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US (3) US7304078B2 (es)
EP (5) EP1860106B1 (es)
JP (2) JP4558331B2 (es)
KR (1) KR101026929B1 (es)
CN (1) CN1659162B (es)
AR (1) AR039570A1 (es)
AT (3) ATE378330T1 (es)
AU (1) AU2003221932B2 (es)
BR (1) BRPI0309309B8 (es)
CA (1) CA2482858C (es)
CY (3) CY1107184T1 (es)
DE (3) DE60331114D1 (es)
DK (2) DK1495018T3 (es)
EC (1) ECSP045368A (es)
ES (3) ES2357876T3 (es)
FR (1) FR15C0047I2 (es)
HK (3) HK1070887A1 (es)
IL (1) IL164585A (es)
LT (1) LTC1495018I2 (es)
LU (1) LU92759I2 (es)
MX (1) MXPA04010308A (es)
MY (1) MY144040A (es)
NL (1) NL300746I2 (es)
NO (2) NO330500B1 (es)
NZ (2) NZ535880A (es)
PE (1) PE20040412A1 (es)
PL (1) PL214718B1 (es)
PT (2) PT1495018E (es)
RU (2) RU2329264C9 (es)
SG (1) SG164279A1 (es)
SI (2) SI1495018T1 (es)
TW (1) TWI343919B (es)
WO (1) WO2003089428A1 (es)
ZA (1) ZA200408342B (es)

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