AR065081A1 - Compuestos de quinazolinona y pirimidona fusionados y composicion farmaceutica - Google Patents

Compuestos de quinazolinona y pirimidona fusionados y composicion farmaceutica

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Publication number
AR065081A1
AR065081A1 ARP080100362A ARP080100362A AR065081A1 AR 065081 A1 AR065081 A1 AR 065081A1 AR P080100362 A ARP080100362 A AR P080100362A AR P080100362 A ARP080100362 A AR P080100362A AR 065081 A1 AR065081 A1 AR 065081A1
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Argentina
Prior art keywords
optionally substituted
heterocyclyl
cycloalkylalkyl
heteroaryl
heteroarylalkyl
Prior art date
Application number
ARP080100362A
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English (en)
Inventor
Qun Sun
Jianmin Fu
Duanjie Hou
Rajender Kamboj
Serguei Sviridov
Robert Fraser
Shifeng Liu
Original Assignee
Xenon Pharmaceuticals Inc
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Application filed by Xenon Pharmaceuticals Inc filed Critical Xenon Pharmaceuticals Inc
Publication of AR065081A1 publication Critical patent/AR065081A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
    • C07D239/88—Oxygen atoms
    • C07D239/91—Oxygen atoms with aryl or aralkyl radicals attached in position 2 or 3
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P23/00—Anaesthetics
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • 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
    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic 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
    • C07D403/04—Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic 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
    • C07D403/12—Heterocyclic 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
    • 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
    • C07D405/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D413/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic 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
    • C07D471/02—Heterocyclic 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
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic 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
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic 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
    • C07D495/04—Ortho-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)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Neurosurgery (AREA)
  • Cardiology (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Anesthesiology (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Estos compuestos, sus estereoisomeros, enantiomeros, tautomeros o sus mezclas; una de sus sales, solvatos o profármacos farmacéuticamente aceptables son utiles para el tratamiento y/o la prevencion de enfermedades o condiciones patologicas mediadas por el canal de sodio, tales como dolor. Reivindicacion 1: Un compuesto de la formula (1), caracterizado porque: n es 1 a 4; el anillo A es un arilo fusionado o un heteroarilo fusionado; cada R1 está seleccionado, de modo independiente, del grupo que consiste en hidrogeno, alquilo, alquenilo, alquinilo, halo, haloalquilo, haloalquenilo, haloalquinilo, cicloalquilo, cicloalquilalquilo, cicloalquilalquenilo, cicloalquilalquinilo, arilo, aralquilo, aralquenilo, aralquinilo, heterociclilo, heterocicliIalquilo, heterociclilalquenilo, heterociclilalquinilo, heteroarilo, heteroarilalquilo, heteroarilalquenilo, heteroarilalquinilo,-R6-CN, -R6-NO2, -R6-OR5, -R6-N(R4)R5, -R6-S(O)pR4, -R6-C(O)R4, -R6-C(S)R4, -R6-C(R4)2C(O)R5, -R6-C(O)OR4, - R6-OC(O)R4, -R6-C(S)OR4, -R6-C(O)N(R4)R5, -R-C(S)N(R4)R5, -R6-N(R5)C(O)R4, -R6-N(R5)C(S)R4, -R6-N(R5)C(O)OR4, -R6-N(R5)C(S)OR4, -R6-N(R5)C(O)N(R4)R5, -R6-N(R5)C(S)N(R4)R5, -R6-N(R5)S(O)tR4, -R6-N(R5)S(O)tN(R4)R5, -R6-S(O)tN(R4)R5, -R6- N(R5)C(=NR5)N(R4)R5, y -R6-N(R5)C(N=C(R4)R5)N(R4)R5, en donde cada p es, de modo independiente, 0, 1 o 2 y cada t es, de modo independiente, 1 o 2, o dos grupos adyacentes R1, junto con los átomos de carbono o heteroanillos a los que están directamente unidos, pueden formar un anillo fusionado seleccionado de cicloalquilo, arilo, heterociclilo o heteroarilo, y los grupos R1 restantes, de estar presentes son como se describieron con anterioridad; R2 es hidrogeno, alquilo, alquenilo, alquinilo, haloalquilo, haloalquenilo, haloalquinilo, cicloalquilo, cicloalquilalquilo, cicloalquilalquenilo, arilo, aralquilo, aralquenilo, aralquinilo, heterociclilo, heterociclilalquilo, heterociclilalquenilo, heterociclilalquinilo, heteroarilo, heteroarilalquilo, heteroarilalquenilo o heteroarilalquinilo; R3 es hidrogeno, alquilo, alquenilo, alquinilo, haloalquilo, haloalquenilo, haloalquinilo, hidroxialquilo, cicloalquilo, cicloalquilalquilo, cicloalquilalquenilo, cicloalquilalquinilo, arilo, aralquilo, aralquenilo, aralquinilo, heterociclilo, heterociclilalquilo, heterociclilalquenilo, heterociclilalquinilo, heteroarilo, heteroarilalquilo, heteroarilalquenilo, heteroarilalquinilo, -R7-N(R4)R5 o -R7-N(R4)C(O)OR4; en donde el grupo cicloalquilo, cicloalquilalquilo, cicloalquilalquenilo, cicloalquilalquinilo, arilo, aralquilo, aralquenilo, aralquinilo, heterociclilo, heterociclilalquilo, heterociclilalquenilo, heterociclilalquinilo, heteroarilo, heteroarilalquilo, heteroarilalquenilo o heteroarilalquinilo puede estar opcionalmente sustituido con uno o varios sustituyentes seleccionados del grupo que consiste en alquilo, alquenilo, alquenilo, alquinilo, halo, haloalquilo, haloalquenilo, haloalquinilo, cicloalquilo opcionalmente sustituido, cicloalquilalquilo opcionalmente sustituido, cicloalquilalquenilo opcionalmente sustituido, cicloalquilalquinilo opcionalmente sustituido, arilo opcionalmente sustituido, aralquilo opcionalmente sustituido, aralquenilo opcionalmente sustituido, aralquinilo opcionalmente sustituido, heterociclilo opcionalmente sustituido, heterociclilalquilo opcionalmente sustituido, heterociclilalquenilo opcionalmente sustituido, heterociclilalquinilo opcionalmente sustituido, heteroarilo opcionalmente sustituido, heteroarilalquilo opcionalmente sustituido, heteroarilalquenilo opcionalmente sustituido, heteroarilalquinilo opcionalmente sustituido, R6-CN, -R6-NO2, -R6-OR5, -R6-OC(O)R4, -R6-OS(O)2R4, -R6-C(O)R4, -R6-C(O)OR4, -R6-C(O)N(R4)R5, -R6-N(R4)R5, -R6-N(R5)C(O)R4, -R6-N(R5)C(O)OR4, -R6-N(R5)C(O)N(R4)R5, -R6-N(R5)S(O)tR4, -R6-N[S(O)tR4]2, -R6-N(R5)C(=NR5)N(R4)R5, -R6-N(R5)C(=NR5)N(R4)CN, -R6-N(R5)C[=NC(O)OR4]-N(R4)-C(O)OR4, -R6-N(R5)-R7-N(R4)R5, -R6- N=C(OR4)R5, -R6-N=C(R4)R5, -R6-N(R5)-, -R6-OR5, -R6-S(O)pR4, y -R6-S(O)tN(R4)R5, en donde cada p es, de modo independiente, 0, 1 o 2 y cada t es, de modo independiente, 1 o 2, cada R4 y R5 está seleccionado, de modo independiente, del grupo que consiste en hidrogeno, alquilo, alquenilo, alquinilo, haloalquilo, hidroxialquilo, alcoxialquilo, cicloalquilo opcionalmente sustituido, cicloalquilalquilo opcionalmente sustituido, arilo opcionalmente sustituido, aralquilo opcionalmente sustituido, heterociclilo opcionalmente sustituido, heterociclilalquilo opcionalmente sustituido, heteroarilo opcionalmente sustituido y heteroarilalquilo opcionalmente sustituido; o R4 y R5, junto con el nitrogeno al que están unidos ambos, forman un N- heterociclilo opcionalmente sustituido o un N-heteroarilo opcionalmente suslituido; cada R6 es un enlace directo, una cadena de alquileno lineal o ramificada opcionalmente sustituida, una cadena de alquenileno lineal o ramificada opcionalmente sustituida o una cadena de alquinileno lineal o ramificada opcionalmente sustituida; y R7 es una cadena de alquileno lineal o ramificada, una cadena de alquenileno lineal o ramificada o una cadena de alquinileno lineal o ramificada; corno uno de sus estereoisomeros, enantiomeros, tautomeros o sus mezclas: o una de sus sales, solvatos o profármacos farmacéuticamente aceptables.
ARP080100362A 2007-01-29 2008-01-29 Compuestos de quinazolinona y pirimidona fusionados y composicion farmaceutica AR065081A1 (es)

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US89118807P 2007-02-22 2007-02-22

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