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AR064031A1 - Compuestos de azaindolilo y metodos de uso - Google Patents

Compuestos de azaindolilo y metodos de uso

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Publication number
AR064031A1
AR064031A1 ARP070105307A ARP070105307A AR064031A1 AR 064031 A1 AR064031 A1 AR 064031A1 AR P070105307 A ARP070105307 A AR P070105307A AR P070105307 A ARP070105307 A AR P070105307A AR 064031 A1 AR064031 A1 AR 064031A1
Authority
AR
Argentina
Prior art keywords
alkyl
cr19r20
nhc
cr14r15
noc
Prior art date
Application number
ARP070105307A
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English (en)
Original Assignee
Genentech Inc
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.)
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Publication date
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Publication of AR064031A1 publication Critical patent/AR064031A1/es

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Classifications

    • 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
    • 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
    • A61P19/02—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
    • 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
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Composiciones y métodos utiles para la inhibicion del crecimiento celular anomalo o el tratamiento de un trastorno hiperproliferativo, o el tratamiento de una enfermedad inflamatoria en un mamífero y métodos de uso de los compuestos para diagnostico o tratamiento de células de mamíferos, o procesos patologicos relacionados, in vitro, in situ e in vivo. Reivindicacion 1: Un compuesto seleccionado a partir de la formula 1: y sales del mismo, donde: Z1 es CR1 o N; Z2 es CR2 o N; Z3 es CR3 o N; Z4 es CR4 o N; donde uno o dos de Z1, Z2, Z3 y Z4 son N; R1, R2, R3 y R4 se seleccionan, independientemente uno de otro, entre H, halo, CN, CF3, -OCF3, -NO2, -(CR14R15)nC(=Y)R11, -(CR14R15)nC(=Y)OR11, -(CR14R15)nC(=Y)NR11R12, -(CR14R15)nNR11R12, - (CR14R15)nOR11, -(CR14R15)nSR11, -(CR14R15)nNR12C(=Y)R11, -(CR14R15)nNR12C(=Y)OR11, -(CR14R15)nNR13C(=Y)NR11R12, -(CR14R15)nNR12SO2R11, -(CR14R15)nOC(=Y)R11, -(CR14R15)nOC(=Y)OR11, -(CR14R15)nOC(=Y)NR11R12, -(CR14R15)nOS(O)2(OR11), - (CR14R15)nOP(=Y)(OR11)(OR12), -(CR14R15)nOP(OR11)(OR12), -(CR14R15)nS(O)R11, -(CR14R15)nS(O)2R11, -(CR14R15)nS(O)2NR11R12, -(CR14R15)nS(O)(OR11), -(CR14R15)nS(O)2(OR11), -(CR14R15)nSC(=Y)R11, -(CR14R15)nSC(=Y)OR11, -(CR14R15)nSC(=Y)NR11R12, alquilo C1-12, alquenilo C2-8, alquinilo C2-8, carbociclilo, heterociclilo, arilo y heteroarilo; W es X1-N-R5- o R11-O-; R5 y R6 se seleccionan independientemente uno de otro entre H o alquilo C1-12; X1 se selecciona entre R11, -OR11, -NR11R12, -S(O)R11 y - S(O)2R11; donde X1 es R11 o -OR11, R11 o -OR11 de X1 se unen opcionalmente a -N-R5 de W para formar un anillo de 4 a 7 subunidades saturado o insaturado con 0 a 2 heteroátomos adicionales seleccionados entre O, S y N, donde este anillo se sustituye opcionalmente por uno o más grupos seleccionados entre halo, CN, CF3, -OCF3, -NO2, oxo, -Si(C1-6 alquil), -(CR19R20)nC(=Y')R16, -(CR19R20)nC(=Y')OR16, -(CR19R20)nC(=Y')NR16R17, -(CR19R20)nNR16R17, -(CR19R20)nOR16, -(CR19R20)n-SR16, - (CR19R20)nNR16C(=Y')R17, -(CR19R20)nNR16C(=Y')OR17, -(CR19R20)nNR18C(=Y')NR16R17, -(CR19R20)nNR17SO2R16, -(CR19R20)nOC(=Y')R16, -(CR19R20)nOC(=Y')OR16, -(CR19R20)nOC(=Y')NR16R17, -(CR19R20)nOS(O)2(OR16), -(CR19R20)nOP(=Y')(OR16)(OR17), - (CR19R20)nOP(OR16)(OR17), -(CR19R20)nS(O)R16, -(CR19R20)nS(O)2R16, -(CR19R20)nS(O)2NR16R17, -(CR19R20)nS(O)(OR16), -(CR19R20)nS(O)2(OR16), -(CR19R20)nSC(=Y')R16, -(CR19R20)nSC(=Y')OR16, -(CR19R20)nSC(=Y')NR16R17 y R21; X2 se selecciona entre carbociclilo, heterociclilo, arilo y heteroarilo; X3 se selecciona entre H, -(CR23R24)nR12, -(CR23R24)qNR11R12, -(CR23R24)qOR12, -(CR23R24)pC(O)NR11R12, -(CR23R24)qNR11C(O)R12, -(CR23R24)pS(O)2NR11R12, y -(CR23R24)qNR11S(O)2R12; R11, R12 y R13 son, independientemente uno de otro, H, alquilo C1-12, alquenilo C2-8, alquinilo C2-8, carbociclilo, heterociclilo, arilo o heteroarilo, o R11 y R12 junto con el nitrogeno al que están unidos forman un anillo saturado, insaturado o aromático de 3 a 8 subunidades con 0 a 2 heteroátomos seleccionados entre O, S y N, donde dicho anillo se sustituye opcionalmente por uno o más grupos seleccionados entre halo, CN, CF3, -OCF3, -NO2, alquilo C1-6, -OH, -SH, -O(alquilo C1-6), -S(alquilo C1-6), -NH2, - NH(alquilo C1-6), -N(alquilo C1-6)2, -SO2(alquilo C1-6), -CO2H, -CO2(alquilo C1-6), -C(O)NH2, -C(O)NH(alquilo C1-6), -C(O)N(alquilo C1-6)2, -N(alquilo C1-6)C(O)(alquilo C1-6), -NHC(O)(alquilo C1-6), -NHSO2(alquilo C1-6), -N(alquilo C1-6)SO2(alquilo C1-6), -SO2NH2, -SO2NH(alquilo C1-6), -SO2N(alquilo C1-6)2, -OC(O)NH2, -OC(O)NH(alquilo C1-6), -OC(O)N(alquilo C1-6)2, -OC(O)O(alquilo C1-6), -NHC(O)NH(alquilo C1-6), -NHC(O)N(alquilo C1-6)2, -N(alquilo C1-6)C(O)NH(alquilo C1-6), -N(alquilo C1- 6)C(O)N(alquilo C1-6)2, -NHC(O)NH(alquilo C1-6), -NHC(O)N(alquilo C1-6)2, -NHC(O)O(alquilo C1-6) y -N(alquilo C1-6)C(O)O(alquilo C1-6); R14 y R15 se seleccionan, independientemente uno de otro, entre H, alquilo C1-12, arilo, carbociclilo, heterociclilo y heteroarilo; m y n se seleccionan independientemente uno de otro entre 0, 1, 2, 3, 4, 5 o 6, p es 1, 2 o 3; q es 2 o 3; Y es independientemente O, NR11 o S; donde cada uno de esos alquilos, alquinilos, carbociclilos, heterociclilos, arilos y heteroarilos de R1, R2, R3, R4, R5, R6, X1, X2, R11, R12, R13, R14 y R15 se sustituye, de forma opcional e independientemente uno de otro, por uno o más grupos seleccionados independientemente uno de otro entre halo, CN, CF3, -OCF3, -NO2, oxo, -Si(alquilo C1-6), -(CR19R20)nC(=Y')R16, -(CR19R20)nC(=Y')OR16, -(CR19R20)nC(=Y')NR16R17, -(CR19R20)nNR16R17, -(CR19R20)nOR16, -(CR19R20)n-SR16, -(CR19R20)nNR16C(=Y')R17, -(CR19R20)nNR16C(=Y')OR17, -(CR19R20)nNR18C(=Y')NR16R17, - (CR19R20)nNR17SO2R16, -(CR19R20)nOC(=Y')R16, -(CR19R20)nOC(=Y')OR16, -(CR19R20)nOC(=Y')NR16R17, -(CR19R20)nOS(O)2(OR16), -(CR19R20)nOP(=Y')(OR16)(OR17), -(CR19R20)nOP(OR16)(OR17), -(CR19R20)nS(O)R16, -(CR19R20)nS(O)2R16, -(CR19R20)nS(O)2NR16R17, - (CR19R20)nS(O)(OR16), -(CR19R20)nS(O)2(OR16), -(CR19R20)nSC(=Y')R16, -(CR19R20)nSC(=Y')OR16, -(CR19R20)nSC(=Y')NR16R17 y R21; cada R16, R17 y R18 es independientemente H, alquilo C1-12, alquenilo C2-8, alquinilo C2-8, carbociclilo, heterociclilo, arilo o heteroarilo, donde dicho alquilo, alquenilo, alquinilo, carbociclilo, heterociclilo, arilo o heteroarilo se sustituye opcionalmente por uno o más grupos seleccionados entre halo, CN, -OCF3, CF3, -NO2, alquilo C1-6, -OH, -SH, -O(alquilo C1- 6), -S(alquilo C1-6), -NH2, -NH(alquilo C1-6), -N(alquilo C1-6)2, -SO2(alquilo C1-6), -CO2H, -CO2(alquilo C1-6), -C(O)NH2, -C(O)NH(alquilo C1-6), -C(O)N(alquilo C1-6)2, -N(alquilo C1-6)C(O)(alquilo C1-6), -NHC(O)(alquilo C1-6), -NHSO2(alquilo C1-6), -N(alquilo C1-6)SO2(alquilo C1-6), -SO2NH2, -SO2NH(alquilo C1-6), -SO2N(alquilo C1-6)2, -OC(O)NH2, -OC(O)NH(alquilo C1-6), -OC(O)N(alquilo C1-6)2, -OC(O)O(alquilo C1-6), -NHC(O)NH(alquilo C1-6), -NHC(O)N(alquilo C1-6)2, -N(alquilo C1- 6)C(O)NH(alquilo C1-6), -N(alquilo C1-6)C(O)N(alquilo C1-6)2, -NHC(O)NH(alquilo C1-6), -NHC(O)N(alquilo C1-6)2, -NHC(O)O(alquilo C1-6) y -N(alquilo C1-6)C(O)O(alquilo C1-6); o R16 y R17 junto con el nitrogeno al que están unidos forman un anillo saturado, insaturado o aromático de 3 a 8 subunidades con 0 a 2 heteroátomos seleccionados entre O, S y N, donde dicho anillo se sustituye opcionalmente por uno o más grupos seleccionados entre halo, CN, -OCF3, CF3, -NO2, alquilo C1-6, -OH, -SH, - O(alquilo C1-6), -S(alquilo C1-6), -NH2, -NH(alquilo C1-6), -N(alquilo C1-6)2, -SO2(alquilo C1-6), -CO2H, -CO2(alquilo C1-6), -C(O)NH2, -C(O)NH(alquilo C1-6), -C(O)N(alquilo C1-6)2, -N(alquilo C1-6)C(O)(alquilo C1-6), -NHC(O)(alquilo C1-6), - NHSO2(alquilo C1-6), -N(alquilo C1-6)SO2(alquilo C1-6), -SO2NH2, -SO2NH(alquilo C1-6), -SO2N(alquilo C1-6)2, -OC(O)NH2, -OC(O)NH(alquilo C1-6), -OC(O)N(alquilo C1-6)2, -OC(O)O(alquilo C1-6), -NHC(O)NH(alquilo C1-6), -NHC(O)N(alquilo C1-6)2, - N(alquilo C1-6)C(O)NH(alquilo C1-6), -N(alquilo C1-6)C(O)N(alquilo C1-6)2, -NHC(O)NH(alquilo C1-6), -NHC(O)N(alquilo C1-6)2, -NHC(O)O(alquilo C1-6) y -N(alquilo C1-6)C(O)O(alquilo C1-6); R19 y R20 se seleccionan independientemente entre H, alquilo C1-12, -(CH2)n-arilo, -(CH2)n-carbociclilo, -(CH2)n-heterociclilo y -(CH2)n-heteroarilo; R21 es alquilo C1-12, alquenilo C2-8, alquinilo C2-8, carbociclilo, heterociclilo, arilo o heteroarilo, donde cada subunidad de R21 se sustituye opcionalmente por uno o más grupos seleccionados entre halo, oxo, CN, -OCF3, CF3, -NO2, alquilo C1-6, -OH, -SH, -O(alquilo C1-6), -S(alquilo C1-6), -NH2, -NH(alquilo C1-6), -N(alquilo C1-6)2, -SO2(alquilo C1-6), -CO2H, -CO2(alquilo C1-6), -C(O)NH2, - C(O)NH(alquilo C1-6), -C(O)N(alquilo C1-6)2, -N(alquilo C1-6)C(O)(alquilo C1-6), -NHC(O)(alquilo C1-6), -NHSO2(alquilo C1-6), -N(alquilo C1-6)SO2(alquilo C1-6), -SO2NH2, -SO2NH(alquilo C1-6), -SO2N(alquilo C1-6)2, -OC(O)NH2, -OC(O)NH(alquilo C1-6), - OC(O)N(alquilo C1-6)2, -OC(O)O(alquilo C1-6), -NHC(O)NH(alquilo C1-6), -NHC(O)N(alquilo C1-6)2, -N(alquilo C1-6)C(O)NH(alquilo C1-6), -N(alquilo C1-6)C(O)N(alquilo C1-6)2, -NHC(O)NH(alquilo C1-6), -NHC(O)N(alquilo C1-6)2, -NHC(O)O(alquilo C1-6) y - N(alquilo C1-6)C(O)O(alquilo C1-6); cada Y' es independientemente O, NR22 o S; R22 es H o alquilo C1-12; y R23 y R24 son independientemente H o alquilo C1-6, donde dicho alquilo se sustituye opcionalmente por uno o más grupos seleccionados entre halo, CN, CF3, -OCF3, -NO2, -OH, -SH, -O(alquilo C1-6), -S(alquilo C1-6), -NH2, -NH(alquilo C1-6), -N(alquilo C1-6)2, -SO2(alquilo C1-6), -CO2H, -CO2(alquilo C1-6), -C(O)NH2, -C(O)NH(alquilo C1-6), -C(O)N(alquilo C1-6)2, -N(alquilo C1-6)C(O)(alquilo C1-6), -NHC(O)(alquilo C1-6), -NHSO2(alquilo C1-6), -N(alquilo C1-6)SO2(alquilo C1-6), -SO2NH2, -SO2NH(alquilo C1-6), -SO2N(alquilo C1-6)2, -OC(O)NH2, -OC(O)NH(alquilo C1-6), -OC(O)N(alquilo C1-6)2, -OC(O)O(alquilo C1-6), -NHC(O)NH(alquilo C1-6), - NHC(O)N(alquilo C1-6)2, -N(alquilo C1-6)C(O)NH(alquilo C1-6), -N(alquilo C1-6)C(O)N(alquilo C1-6)2, -NHC(O)NH(alquilo C1-6), -NHC(O)N(alquilo C1-6)2, -NHC(O)O(alquilo C1-6) y -N(alquilo C1-6)C(O)O(alquilo C1-6).
ARP070105307A 2006-11-30 2007-11-29 Compuestos de azaindolilo y metodos de uso AR064031A1 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US86805506P 2006-11-30 2006-11-30
US91762007P 2007-05-11 2007-05-11
US94474307P 2007-06-18 2007-06-18

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AR064031A1 true AR064031A1 (es) 2009-03-04

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US (1) US7855216B2 (es)
EP (1) EP2099796B1 (es)
JP (1) JP5211063B2 (es)
AR (1) AR064031A1 (es)
AT (1) ATE511509T1 (es)
AU (1) AU2007325123B2 (es)
CA (1) CA2672327A1 (es)
CL (1) CL2007003444A1 (es)
DK (1) DK2099796T3 (es)
PE (1) PE20081354A1 (es)
PL (1) PL2099796T3 (es)
PT (1) PT2099796E (es)
TW (1) TW200829586A (es)
WO (1) WO2008067481A1 (es)

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AU2007325123B2 (en) 2012-12-13
EP2099796A1 (en) 2009-09-16
WO2008067481A1 (en) 2008-06-05
PT2099796E (pt) 2011-09-06
CL2007003444A1 (es) 2008-06-27
TW200829586A (en) 2008-07-16
US7855216B2 (en) 2010-12-21
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PL2099796T3 (pl) 2011-10-31
JP2010511626A (ja) 2010-04-15
US20080242655A1 (en) 2008-10-02
CA2672327A1 (en) 2008-06-05
HK1135099A1 (en) 2010-05-28
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AU2007325123A1 (en) 2008-06-05
DK2099796T3 (da) 2011-09-05

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