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CO5261601A1 - Indolilquinolinonas utiles como inhibidores de la tirosinoquinasa - Google Patents

Indolilquinolinonas utiles como inhibidores de la tirosinoquinasa

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Publication number
CO5261601A1
CO5261601A1 CO00079309A CO00079309A CO5261601A1 CO 5261601 A1 CO5261601 A1 CO 5261601A1 CO 00079309 A CO00079309 A CO 00079309A CO 00079309 A CO00079309 A CO 00079309A CO 5261601 A1 CO5261601 A1 CO 5261601A1
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Colombia
Prior art keywords
alkyl
aob
aryl
cycloalkyl
heterocyclyl
Prior art date
Application number
CO00079309A
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English (en)
Inventor
Kenneth L Arrington
Mark T Bilodeau
Mark E Fraley
George D Hartman
William F Hoffman
Randall W Hungate
Yuntae Kim
Original Assignee
Merck & Co Inc
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Filing date
Publication date
Application filed by Merck & Co Inc filed Critical Merck & Co Inc
Publication of CO5261601A1 publication Critical patent/CO5261601A1/es

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    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P17/00—Drugs for dermatological disorders
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    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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    • 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
    • C—CHEMISTRY; METALLURGY
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    • 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
    • C07D401/06—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 carbon chain containing only aliphatic carbon atoms
    • 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
    • C07D405/14—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
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic 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
    • 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)
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  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Diabetes (AREA)
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  • Epidemiology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Dermatology (AREA)
  • Immunology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
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  • Psychiatry (AREA)
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Abstract

Un compuesto de Fórmula I <EMI FILE="00079309_1" ID="1" IMF=JPEG >ó una sal farmacéuticamente aceptable ó estereoisómero de éste, en donde <EMI FILE="00079309_2" ID="2" IMF=JPEG > Z es W1 es S, O, ó N-R; V1 es N ó C; W2 es N ó C; V2 es S, O, ó N-R; a es 0 ó 1; b es 0 ó 1; m es 0, 1, ó 2; s es 1 ó 2; t es 1,2, ó 3; X=Y es C=N, N=C, ó C=C; R es H ó alquil C1-6; R1 y R5 se seleccionan independientemente entre: 1) H, 2) (C=O)aOb-alquil C1-C10,3) (C=O)aOb-aril, 4) (C=O)aOb-alquenil C2-C10, 5) (C=O)aOb-alquinil C2-C10, 6) CO2H, 7) halo, 8) OH, 9) Ob-perfluoroalquil C1-C6, 10) (C=O)aNR7R8 11) CN, - 2 -12) (C=O)aOb-cicloalquil C3-C8, y 13) (C=O)aOb-heterociclil, en donde dichos grupos alquil, aril, alquenil, alquinil, cicloalquil, y heterociclil van opcionalmente sustituidos con uno ó más sustituyentes seleccionados entre grupos R6; R2 y R3 se seleccionan independientemente entre: 1) H, 2) (C=O)aalquil C1-C6,3) (C=O)Oa-aril, 4) alquil C1-C6, 5) SO2Ra, y 6) aril; R4 se selecciona entre: 1) (C=O)aOb-alquil C1-C10, 2) (C=O)aOb-aril, 3) (C=O)aOb-alquenil C2-C10, 4) (C=O)aOb-alquinil C2-C10, 5) CO2H 6) halo, 7) OH, 8) Ob-perfluoroalquil C1-C6, 9) (C=O)aNR7R8, 10) CN, 11) (C=O)aOb-cicloalquil C3-C8, y 12) (C=O)aOb-heterociclil, en donde dichos grupos alquil, aril, alquenil, alquinil, cicloalquil, y heterociclil van opcionalmente sustituidos con uno ó más sustituyentes seleccionados entre grupos R6; R6 es: 1) (C=O)aOb-alquil C1-C10, 2) (C=O)aOb-aril, 3) alquenil C2-C10, 4) alquinil C2-C10, 5) (C=O)aOb-heterociclil, 6) CO2H, 7) halo, 8) CN, 9) OH, 10) Ob-perfluoroalquil C1-C6, 11) 0a(C=O)bNR7R8, 12) oxo, 13) CHO, 14) (N=O)R7R8, ó 15) (C=O)aOb-cicloalquil C3-C8, en donde dichos grupos alquil, aril, alquenil, alquinil, heterociclil, y cicloalquil van opcionalmente sustituidos con uno ó más sustituyentes seleccionados entre grupos R6a; R6a se selecciona entre: 1) (C=O)rOs-alquil(C1-C10), en donde r y s son independientemente 0 ó 1,2) Or-petfluoroalquil (C1-C3), en donde r es 0 ó 1, 3) alquileno (C0-C6)-S(O)mRa, en donde m es 0, 1, ó 2, 4) oxo, 5) OH, 6) halo, 7) CN, 8) alquenil (C2-C10), 9) alquinil (C2-C10), 10) cicloalquil(C3-C6), 11) alquileno (C0-C6)-aril, 12) alquileno (C0-C6)-heterociclil, 13) alquileno (C0-C6)-N(Rb)2, 14) C(O)Ra, 15) alquileno (C0-C6)-CO2Ra, 16) C(O)H, y 17) alquileno (C0-C6)-CO2H, en donde dichos grupos alquil, alquenil, alquinil, cicloalquil, aril, y heterociclil van opcionalmente sustituidos con hasta tres sustituyentes seleccionados entre Rb, OH, alcoxi (C1-C6), halógeno, CO2H, CN, O(C=O)-alquil C1-C6, oxo, y N(Rb)2; R7 y R8 se seleccionan independientemente entre: 1) H, 2) (C=O)Ob-alquil C1-C6, 3) (C=O)Ob-cicloalquil C3-C8, 4) (C=O)Ob-aril 5) (C=O)Ob-heterociclil, 6) alquil C1-C10, 7) aril, 8) alquenil C2-C10, 9) alquinil C2-C10, 10) heterociclil, 11) cicloalquil C3-C8 - 3 - 12) SO2Ra, y 13 (C=O)NRb2, en donde dichos grupos alquil, cicloalquil, aril, heterocilil, alquenil, y alquinil van opcionalmente sustituidos con uno ó más sustituyentes seleccionados entre grupos R6a, ó R7 y R8 pueden tomarse junto con el nitrógeno al cual van ligados para formar un heterociclo monocíclico ó bicíclico con 5 - 7 miembros en cada anillo y que opcionalmente contiene, además del nitrógeno, uno ó dos heteroátomos adicionales seleccionados entre N, O y S, dicho heterociclo monocíclico ó bicíclico opcionalmente sustituido con uno ó más sustituyentes seleccionados entre grupos R6a; Ra es alquil (C1-C6), cicloalquil (C3-C6), aril, ó heterociclil; y Rb es H, alquil (C1-C6), aril, heterociclil, cicloalquil (C3-C6), (C=O)O-alquil C1-C6, (C=(O)alquil C1-C6 ó S(O)2Ra.
CO00079309A 1999-10-19 2000-10-18 Indolilquinolinonas utiles como inhibidores de la tirosinoquinasa CO5261601A1 (es)

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CO5261601A1 true CO5261601A1 (es) 2003-03-31

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